Datasets:

BioDEX

/

raw_dataset

like 2

{ "abstract": "Dermatomyositis (DM) is an idiopathic autoimmune connective disease characterized by muscles and skin inflammation of and a well-recognized association with several human malignancies, especially breast cancer. Paclitaxel is a taxane antineoplastic agent with therapeutic effects against a wide range of cancers including breast cancer. This drug is well known for neurotoxicity and hypersensitivity reactions. However, cutaneous drug eruptions, especially those of grade III or higher, are not frequent. Here, we describe the case of a 55-year-old woman with metastatic breast cancer who developed paraneoplastic DM and a paclitaxel-induced exanthematous drug eruption. This case report emphasizes the importance of evaluating internal malignancies, such as advanced breast cancer, in newly developed DM patients. In addition, it presents a rare case of paclitaxel-induced exanthematous drug eruption. The purpose of this case report highlights the immunological pathogenic mechanism of DM and drug eruption in underlying advanced breast cancer.", "affiliations": "Department of Internal Medicine, Incheon Sarang Hospital, Incheon, Korea.;Department of Internal Medicine, Incheon Sarang Hospital, Incheon, Korea.;Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.", "authors": "Kim|Youngji|Y|;Jung|Woojin|W|;Park|Yeon Hee|YH|", "chemical_list": null, "country": "Korea (South)", "delete": false, "doi": "10.4048/jbc.2015.18.2.195", "fulltext": "\n==== Front\nJ Breast CancerJ Breast CancerJBCJournal of Breast Cancer1738-67562092-9900Korean Breast Cancer Society 10.4048/jbc.2015.18.2.195Case ReportDermatomyositis and Paclitaxel-Induced Cutaneous Drug Eruption Associated with Metastatic Breast Cancer Kim Youngji Jung Woojin Park Yeon Hee 1Department of Internal Medicine, Incheon Sarang Hospital, Incheon, Korea.1 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.Correspondence to: Yeon Hee Park. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 135-710, Korea. Tel: +82-2-3410-3459, Fax: +82-2-3410-1754, yhparkhmo@skku.edu6 2015 26 6 2015 18 2 195 199 29 7 2014 24 12 2014 © 2015 Korean Breast Cancer Society. All rights reserved.2015This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Dermatomyositis (DM) is an idiopathic autoimmune connective disease characterized by muscles and skin inflammation of and a well-recognized association with several human malignancies, especially breast cancer. Paclitaxel is a taxane antineoplastic agent with therapeutic effects against a wide range of cancers including breast cancer. This drug is well known for neurotoxicity and hypersensitivity reactions. However, cutaneous drug eruptions, especially those of grade III or higher, are not frequent. Here, we describe the case of a 55-year-old woman with metastatic breast cancer who developed paraneoplastic DM and a paclitaxel-induced exanthematous drug eruption. This case report emphasizes the importance of evaluating internal malignancies, such as advanced breast cancer, in newly developed DM patients. In addition, it presents a rare case of paclitaxel-induced exanthematous drug eruption. The purpose of this case report highlights the immunological pathogenic mechanism of DM and drug eruption in underlying advanced breast cancer.\n\nBreast neoplasmsDermatomyositisDrug eruptionsImmunityPaclitaxel\n==== Body\nINTRODUCTION\nThe incidence of dermatomyositis (DM) is reported to be approximately 1/100,000. The majority of cases are idiopathic. However, in approximately 15% to 30% of adult-onset DM cases, DM represents a paraneoplastic syndrome caused by an underlying malignancy [12]. The immune mechanisms involved in DM are undetermined, but are supported by the presence of T cells, macrophages, and dendritic cells in muscle tissue. T cells may have direct and indirect toxic effects on muscle fibers, causing muscle fiber necrosis and muscle weakness, but the target of the immune reaction is unknown [3].\n\nExanthematous drug eruptions are the most common form of drug-induced cutaneous eruptions. These reactions begin 4 to 21 days after the culprit drug is administered and rapidly evolve into widespread rashes, while recurrence after rechallenge begins within 2 days. This onset pattern suggests that rather than direct toxicity, sensitization and specific immunological memory occur when a dose-related threshold is reached. Resolution after drug discontinuation (known as \"dechallenge\") also helps identify the causative agent [45]. Management includes discontinuation of the culprit drug and antipruritic therapy. The spectrum of medications reported to cause drug-induced exanthema is wide and includes drugs of multiple classes, most commonly antibiotics.\n\nOur patient presented with DM as a paraneoplastic syndrome associated with metastatic breast cancer. Two years later, she experienced an exanthematous drug eruption that was related to paclitaxel-based palliative chemotherapy.\n\nHere, we describe a patient with metastatic breast cancer who developed paraneoplastic DM and an exanthematous drug eruption after exposure to paclitaxel. To the best of our knowledge, there have been few reported cases of adverse drug reactions in which morbilliform exanthema was induced by paclitaxel.\n\nCASE REPORT\nIn May 2011, a 55-year-old postmenopausal woman presented to a community hospital for the evaluation of polyarthralgia and erythematous skin rashes with itching sensation. She was a never smoker and not an alcoholic, and had a history of situs inversus totalis diagnosed at the age of 33 years. The rash was initially diagnosed as rheumatic dermatitis and treated with oral steroids and antihistamines with slight improvement. At that time, her physician in charge coincidentally noticed a palpable nodule in the left breast. A diagnostic core needle biopsy revealed invasive ductal carcinoma in the left breast (Figure 1A). The tumor was negative for estrogen and progesterone receptors. HER2/neu expression was immunohistochemically positive (Figure 1B). A computed tomography scan of the chest, abdomen, and pelvis and a bone scan showed multiple lymph node metastases (Figure 2). She was referred to our breast clinic for further oncologic evaluation and care. In our clinic, she was diagnosed with DM accompanying cutaneous erythematous eruptions, heliotropic rashes over both upper eyelids, Gottron's papules on both elbows, and progressive weakness/arthralgia of the upper and lower limbs. The patient's complete blood cell count and differential, urinalysis, electrolytes, hepatitis serology, myoglobulin, anti-Jo-1 antibody, extractable nuclear antigen I (ENA I) antibody, ENA II antibody, and anti-cyclic citrullinated peptide antibody were within the normal range.\n\nAlanine transaminase and lactate dehydrogenase levels were elevated (83 U/L and 1,560 IU/L, respectively). Antinuclear antibody was weakly positive (1:40). The skin biopsy specimen taken from the left hip showed perivascular lymphocyte and neutrophil infiltration with small, dark nuclei and scant cytoplasm, which was consistent with DM (Figure 3). Since the above test results were consistent with probable DM according to diagnostic criteria [6], a muscle biopsy and electromyogram were not performed.\n\nThe patient was treated with systemic steroid therapy with good control of joint pain and weakness as well as partial remission of skin rashes. The breast cancer was at stage IIIC (cT1N3M0) as assessed using the American Joint Committee on Cancer classification. She received palliative chemotherapy for 2 years as part of the clinical trial MARRIANE study (TDM1 and pertuzumab). She tolerated the breast cancer therapy well, with all manifestations of DM resolving after chemotherapy. After the completion of 37 sessions of palliative chemotherapy, the tumor showed further progression. Skin manifestations of DM occasionally recur in association with significant stressors, but she experienced no recurrence of symptoms suggestive of myositis after chemotherapy. She subsequently received second-line taxane-based chemotherapy with paclitaxel 175 mg/m2 IV over 24 hours and trastuzumab 4 mg/kg, every 3 weeks. Nine days after the first-cycle infusion, multiple erythemaotus maculopapular rashes developed on the whole body symmetrically sparing the palms and soles (Figure 4A). Routine blood tests demonstrated anemia and eosinophilia (hemoglobin 10.8 g/dL, absolute lymphocyte count 1,116×103/µL, neutrophil count 12.0×103/µL, platelet count 189×103/µL). Her vital signs were normal (blood pressure, 110/68 mm Hg; heart rate, 110/min; and temperature, 36.7℃). There was no sign of infection. There was no mucous membrane involvement (ocular, oral, or genital lesions) or nail change. She had not taken any medications. The patient was treated with supportive management, especially systemic steroids and antihistaminics, and the skin rashes gradually resolved over 1 week. She subsequently received paclitaxel 80 mg/m2 per week. However, 5 minutes after her second-cycle infusion of paclitaxel at reduced doses, she complained of skin rashes with itching sensation on the whole body (Figure 4B). Immediately after the cessation of paclitaxel infusion, she was treated with systemic steroids and antihistamines. Her cutaneous lesions improved, and paclitaxel therapy was then stopped after two cycles. Since she was receiving no other medication, associations between exanthema and paclitaxel were suggested by the complete resolution of the skin lesions within weeks of drug withdrawal. The clinical features were consistent with a drug-induced morbilli-form exanthema, and critical assessment disclosed circumstantial evidence to implicate paclitaxel as the cause of this complication [45]. Thus, after first- and second-cycle chemotherapy, her skin rashes were diagnosed as paclitaxel-induced exanthema. The exanthematous drug eruption did not recur after paclitaxel discontinuation. At that time, doxorubicin chemotherapy was planned, and the patient continued to have regular follow-up.\n\nDISCUSSION\nAutoimmune diseases may develop in patients with malignancies through diverse mechanisms. They may occasionally be associated with serious clinical entities. The emergence of these entities may be attributed to autoantibodies generation, paraneoplastic syndromes, direct invasion of the joints and muscles by tumor cells, or combination chemotherapy [7]. With significant advances in immunomodulatory therapies for cancer and autoimmune disease numerous investigators have attempted to understand the role of the human immune system in cancer and autoimmune disease [8].\n\nAfter a cutaneous presentation of DM associated with metastatic breast cancer, our patient experienced a cutaneous exanthematous drug eruption to paclitaxel. The exact pathogenetic mechanisms of DM and adverse drug reactions have not been determined. However, it is speculated that there is a possible biological association between DM and malignancy. It has been suggested that a common environmental factor may simultaneously act as a trigger of inflammation and as a carcinogen. Some investigators have implicated an antitumoral immune reaction that evolves into an autoimmune syndrome through interactions between muscle and skin antigens [9].\n\nPaclitaxel, which is thought to have caused the drug eruption in this case, is an antineoplastic agent for various malignancies. Major adverse reactions include peripheral neuropathy, myelotoxicity, bradycardia and hypotension, alopecia, nausea and emesis, arthralgia and myalgia, granulocytopenia, and hypersensitivity [10]. However, there have been few cases of exanthematous drug eruption to paclitaxel in the literature. Clinicians have suspected for years that drug reactions are mediated by immune mechanisms because their occurrence suggests sensitization and specific immunological memory rather than direct toxicity [11]. It is possible that granulysin is expressed at different levels in multiple cutaneous adverse drug reactions and that skin-infiltrating CD8+ T and NKp46+ cells are prominent sources of granulysin [712].\n\nA strong relationship between autoimmmunological pathogenesis and underlying malignancy has been demonstrated in the literature [89].\n\nNumerous observations suggest that the immune system inhibits cancer progression. For example, when patients are on long-term immunosuppressive medications, for example cyclosporine for the prevention of graft-versus-host disease after organ transplantation, the odds of cancer development is increased. Patients who are immunocompromised by human immunodeficiency virus infection are more susceptible to certain malignancies, including acquired immunodeficiency syndrome-defining cancers such as Kaposi sarcoma and central nervous system lymphomas as well as lung cancer and Hodgkin lymphoma. In addition, similar to the introduction a novel virus into a population, cancer in transplanted organs may develop rapidly in recipients even though malignancies were unapparent or in remission in the donor.\n\nOn a cellular level, T-cells in the tumor environment contribute to antitumor immune activity by interacting with antigen- presenting molecules displaying tumor-associated antigens (TAA), antigenic proteins expressed by a tumor that are unique, and with mutated or even normal self-proteins with upregulated expression. In response to interactions with TAA, tumor-infiltrating lymphocytes (TIL) may produce effector molecules, including granzymes, perforins, cytokines, and interferon γ that are directly cytotoxic to tumor cells. In a few studies, the detection of TIL in most tumors directly correlates with improved prognosis and patient survival, and ideally, this interaction completely eliminate the neoplasm. If the immune system does not kill the malignant growth, it may become clinically significant. Conversely, successful antitumor responses may cross-react with normal self-tissues, leading to the loss of self-tolerance. Consequently, if the magnitude of the immune response continues to grow, inflammatory or autoimmune disease may develop [9].\n\nOur case report reviewed and investigated the immunological pathogenesis of DM and drug eruption, suggesting associated pathways between these entities.\n\nIn conclusion, we have shown that underlying malignancy may represent a favorable soil for rare immunological reactions such as paraneoplastic DM or a cutaneous drug eruption to paclitaxel. In addition, our case underscores the importance of being vigilant for varied forms of associated immunological reactions in patients with internal malignancy.\n\nHowever, the exact pathophysiological mechanisms behind DM and drug eruption, as seen in our patient, have been the subject of controversy. Although DM and drug eruption are allergic and immune-processes, their specific mechanisms require clarification in further studies.\n\nCONFLICT OF INTEREST: The authors declare that they have no competing interests.\n\nFigure 1 A diagnostic core needle biopsy for carcinoma in the left breast. (A) H&E stain revealed invasive ductal (×200). (B) HER2/neu expression was positive by immunohistochemistry (×200).\nFigure 2 Radiologic findings for chest computed tomography (CT). CT scan shows the primary breast cancer of the left breast (A) and multiple lymphadenopathies of the left axilla (B), mediastinum (C, D), right axilla (E), and paratrachea (F). Arrows indicate enlarged lymph nodes and mass.\nFigure 3 Microscopic findings for skin biopsy. (A) Perivascular and interstitial lymphocytic infiltration with small, dark nuclei and scant cytoplasm, are compatible with dermatomyositis (H&E stain, ×400). (B) Aggregates of mature lymphocytes are seen surrounding vessels (H&E stain, ×200).\nFigure 4 Gross findings for paclitaxel induced drug eruption. (A) A skin lesion presented as generalized exanthematous rashes on the trunk (upper) and extremities (lower) 9 days after the first exposure to paclitaxel. (B) A skin lesion became milder 5 minutes after the second exposure to paclitaxel.\n==== Refs\n1 Callen JP Hyla JF Bole GG Jr Kay DR The relationship of dermatomyositis and polymyositis to internal malignancy Arch Dermatol 1980 116 295 298 7369745 \n2 Barnes BE Mawr B Dermatomyositis and malignancy: a review of the literature Ann Intern Med 1976 84 68 76 1106291 \n3 Venalis P Lundberg IE Immune mechanisms in polymyositis and dermatomyositis and potential targets for therapy Rheumatology (Oxford) 2014 53 397 405 23970542 \n4 Bigby M Jick S Jick H Arndt K Drug-induced cutaneous reactions: a report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982 JAMA 1986 256 3358 3363 2946876 \n5 Stern RS Clinical practice. Exanthematous drug eruptions N Engl J Med 2012 366 2492 2501 22738099 \n6 Pectasides D Koumpou M Gaglia A Pectasides M Lambadiari V Lianos E Dermatomyositis associated with breast cancer Anticancer Res 2006 26 2329 2331 16821611 \n7 Rozieres A Vocanson M Saïd BB Nosbaum A Nicolas JF Role of T cells in nonimmediate allergic drug reactions Curr Opin Allergy Clin Immunol 2009 9 305 310 19474707 \n8 Abu-Shakra M Buskila D Ehrenfeld M Conrad K Shoenfeld Y Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies Ann Rheum Dis 2001 60 433 441 11302861 \n9 Franks AL Slansky JE Multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases and cancer Anticancer Res 2012 32 1119 1136 22493341 \n10 Rowinsky EK Cazenave LA Donehower RC Taxol: a novel investigational antimicrotubule agent J Natl Cancer Inst 1990 82 1247 1259 1973737 \n11 Roujeau JC Immune mechanisms in drug allergy Allergol Int 2006 55 27 33 17075283 \n12 Schlapbach C Zawodniak A Irla N Adam J Hunger RE Yerly D NKp46+ cells express granulysin in multiple cutaneous adverse drug reactions Allergy 2011 66 1469 1476 21819408\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "1738-6756", "issue": "18(2)", "journal": "Journal of breast cancer", "keywords": "Breast neoplasms; Dermatomyositis; Drug eruptions; Immunity; Paclitaxel", "medline_ta": "J Breast Cancer", "mesh_terms": null, "nlm_unique_id": "101314183", "other_id": null, "pages": "195-9", "pmc": null, "pmid": "26155297", "pubdate": "2015-06", "publication_types": "D002363:Case Reports", "references": "1973737;7369745;16821611;19474707;23970542;1106291;17075283;11302861;22738099;21819408;2946876;22493341", "title": "Dermatomyositis and Paclitaxel-Induced Cutaneous Drug Eruption Associated with Metastatic Breast Cancer.", "title_normalized": "dermatomyositis and paclitaxel induced cutaneous drug eruption associated with metastatic breast cancer" }

[ { "companynumb": "KR-FRESENIUS KABI-FK201503782", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "077574", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "175", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL (MANUFACTURER UNKNOWN)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TRASTUZUMAB" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TRASTUZUMAB" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "077574", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "80", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL (MANUFACTURER UNKNOWN)" } ], "patientagegroup": null, "patientonsetage": "55", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Dermatomyositis", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug eruption", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "YOUNGJI K,JUNG W,PARK Y. DERMATOMYOSITIS AND PACLITAXEL-INDUCED CUTANEOUS DRUG ERUPTION ASSOCIATED WITH METASTATIC BREAST CANCER. JOURNAL OF BREAST CANCER 2015 JUN;18(2):195-199.", "literaturereference_normalized": "dermatomyositis and paclitaxel induced cutaneous drug eruption associated with metastatic breast cancer", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20150810", "receivedate": "20150810", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11362378, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20151125" }, { "companynumb": "KR-ACCORD-032372", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "075436", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": "IN 1ST CYCLE,RECEIVED PACLITAXEL 175 MG/M2 OVER 24 HOURS, IN 2ND CYCLE REDUCED DOSE TO 80MG/M2/WEEK.", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Drug eruption" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "175", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL/PACLITAXEL LIPOSOME" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TRASTUZUMAB" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": [ { "drugrecuraction": "Drug eruption" } ], "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "4", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TRASTUZUMAB" } ], "patientagegroup": null, "patientonsetage": "55", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug eruption", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Anaemia", "reactionmeddraversionpt": "18.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Eosinophilia", "reactionmeddraversionpt": "18.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "KIM Y, JUNG W, PARK YH. DERMATOMYOSITIS AND PACLITAXEL-INDUCED CUTANEOUS DRUG ERUPTION ASSOCIATED WITH METASTATIC BREAST CANCER. J BREAST CANCER. 2015 JUN;18(2):195-9.", "literaturereference_normalized": "dermatomyositis and paclitaxel induced cutaneous drug eruption associated with metastatic breast cancer", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20150723", "receivedate": "20150723", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11295003, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20151125" } ]

{ "abstract": "Immune checkpoint inhibitors (ICIs) are effective for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, an unconventional response pattern is sometimes encountered. A dissociated response (DR), characterized by some lesions shrinking and others growing, has been recognized with ICI treatment. In this study, we examined the characteristics and treatment outcomes of DR in previously treated NSCLC patients, receiving nivolumab monotherapy. We conducted a retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab. We assessed the tumor response of each organ using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at the first radiologic evaluation. We investigated treatment outcome and compared overall survival using the Kaplan-Meier Method and log-rank tests. Further, we conducted the same analysis in patients who had previously received chemotherapy or tyrosine kinase inhibitor therapy in our hospital. Between April 2016 and September 2018, 107 patients who received nivolumab fulfilled the inclusion criteria. Of them, 5 (5%) patients showed a DR. There were no specific differences in characteristics between DR and non-DR cases. Patients showing DR had significantly longer overall survival than those showing concordant progressive disease (46.9 vs. 8.2 months, p = 0.038). The frequencies of DR in the ICI, chemotherapy, and tyrosine kinase inhibitor-treated cohorts were 5%, 1%, and 4%, respectively. DR was uncommon, but this presented a distinctive pattern of nivolumab response. Some patients might benefit from continuing nivolumab therapy and may achieve a longer overall survival.", "affiliations": "Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan. yuki1130sato@gmail.com.;Department of Clinical Research Center, Kobe City Medical Center General Hospital, Kobe, 650-0047, Japan.;Department of Clinical Pathology, Kobe City Medical Center General Hospital, Kobe, 650-0047, Japan.;Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.;Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.;Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.;Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.;Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.", "authors": "Sato|Yuki|Y|0000-0002-7829-7524;Morimoto|Takeshi|T|;Hara|Shigeo|S|;Nagata|Kazuma|K|;Hosoya|Kazutaka|K|;Nakagawa|Atsushi|A|;Tachikawa|Ryo|R|;Tomii|Keisuke|K|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1007/s10637-021-01077-7", "fulltext": null, "fulltext_license": null, "issn_linking": "0167-6997", "issue": "39(4)", "journal": "Investigational new drugs", "keywords": "Dissociated response; Immune checkpoint inhibitor; Immunotherapy; Mixed response; Nivolumab; Non-small cell lung cancer", "medline_ta": "Invest New Drugs", "mesh_terms": null, "nlm_unique_id": "8309330", "other_id": null, "pages": "1170-1178", "pmc": null, "pmid": "33566254", "pubdate": "2021-08", "publication_types": "D016428:Journal Article", "references": "30620402;18452692;26028407;26412456;30657859;30468872;29738824;27827313;30977778;19934295;29182990;28679767;26762738;16105816;24513263;19097774;28271869;24342626;15945101;29893264;29763666;31675272;25806267;30735003;28126915;22673630", "title": "Dissociated response and clinical benefit in patients treated with nivolumab monotherapy.", "title_normalized": "dissociated response and clinical benefit in patients treated with nivolumab monotherapy" }

[ { "companynumb": "JP-BRISTOL-MYERS SQUIBB COMPANY-BMS-2021-024448", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "NIVOLUMAB" }, "drugadditional": null, "drugadministrationroute": "041", "drugauthorizationnumb": "125554", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "NON-SMALL CELL LUNG CANCER RECURRENT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OPDIVO" } ], "patientagegroup": null, "patientonsetage": "68", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SATO Y, MORIMOTO T, HARA S, NAGATA K, HOSOYA K, NAKAGAWA A, ET AL. DISSOCIATED RESPONSE AND CLINICAL BENEFIT IN PATIENTS TREATED WITH NIVOLUMAB MONOTHERAPY. INVESTIGATIONAL NEW DRUGS. 2021", "literaturereference_normalized": "dissociated response and clinical benefit in patients treated with nivolumab monotherapy", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20210329", "receivedate": "20210312", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19002704, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "JP-BRISTOL-MYERS SQUIBB COMPANY-BMS-2021-022918", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "NIVOLUMAB" }, "drugadditional": null, "drugadministrationroute": "041", "drugauthorizationnumb": "125554", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG ADENOCARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OPDIVO" } ], "patientagegroup": null, "patientonsetage": "53", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SATO Y, MORIMOTO T, HARA S, NAGATA K, HOSOYA K, NAKAGAWA A, ET AL. DISSOCIATED RESPONSE AND CLINICAL BENEFIT IN PATIENTS TREATED WITH NIVOLUMAB MONOTHERAPY. INVESTIGATIONAL NEW DRUGS. 2021", "literaturereference_normalized": "dissociated response and clinical benefit in patients treated with nivolumab monotherapy", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20210324", "receivedate": "20210313", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19005315, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" } ]

{ "abstract": "A 52 year-old male patient diagnosed of ankylosing spondylitis presented with an iron deficiency anemia after a ten-month treatment of methotrexate. He did not respond to treatment with oral iron not a proton pump inhibitor and an upper endoscopy was performed. The histological study of the duodenal biopsies showed villus atrophy. After removing the methotrexate, administering intramuscular iron and undertaking a gluten-free diet, the histological and analytical alterations progressively resolved.", "affiliations": "Gastroenterology Department, Hospital Clinic Universitari of Valencia, Universitat de Valencia Avda. Blasco Ibanez 17 46010 Valencia, Spain. maiabosca@yahoo.es.", "authors": "Boscá|Marta Maia|MM|;Añón|Ramon|R|;Mayordomo|Empar|E|;Villagrasa|Rosana|R|;Balza|Nelly|N|;Amorós|Cirilo|C|;Corts|Juan Ramon|JR|;Benages|Adolfo|A|", "chemical_list": "D018501:Antirheumatic Agents; D008727:Methotrexate", "country": "United States", "delete": false, "doi": "10.3748/wjg.14.7009", "fulltext": null, "fulltext_license": null, "issn_linking": "1007-9327", "issue": "14(45)", "journal": "World journal of gastroenterology", "keywords": null, "medline_ta": "World J Gastroenterol", "mesh_terms": "D018501:Antirheumatic Agents; D001284:Atrophy; D001706:Biopsy; D002446:Celiac Disease; D004386:Duodenum; D016099:Endoscopy, Gastrointestinal; D006801:Humans; D008297:Male; D008727:Methotrexate; D008875:Middle Aged; D013167:Spondylitis, Ankylosing; D013577:Syndrome", "nlm_unique_id": "100883448", "other_id": null, "pages": "7009-11", "pmc": null, "pmid": "19058340", "pubdate": "2008-12-07", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "11796853;16385254;14992437;12806628;12695153;15467310;7566289", "title": "Methotrexate induced sprue-like syndrome.", "title_normalized": "methotrexate induced sprue like syndrome" }

[ { "companynumb": "ES-PFIZER INC-2009197069", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200210", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "METHOTREXATE SODIUM" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "011719", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "15 MG, WEEKLY", "drugenddate": "200307", "drugenddateformat": "610", "drugindication": "ANKYLOSING SPONDYLITIS", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "200210", "drugstartdateformat": "610", "drugstructuredosagenumb": "15", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE SODIUM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "OMEPRAZOLE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMEPRAZOLE." } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Intestinal villi atrophy", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Malabsorption", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 200305" } }, "primarysource": { "literaturereference": "BOSCA, M.. METHOTREXATE INDUCED SPRUE?LIKE SYNDROME. WORLD JOURNAL OF GASTROENTEROLOGY. 2008?14(45):7009?7011", "literaturereference_normalized": "methotrexate induced sprue like syndrome", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20210325", "receivedate": "20210325", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19056891, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" } ]

{ "abstract": "OBJECTIVE\nTo investigate the occurrence of Trichosporon asahii fungemia among critically ill COVID-19 patients.\n\n\nMETHODS\nFrom 1 July to 30 September 2020, cases of T asahii fungemia (TAF) in a Brazilian COVID-19 referral centre were investigated. The epidemiology and clinical courses were detailed, along with a mycological investigation that included molecular species identification, haplotype diversity analysis and antifungal susceptibility testing.\n\n\nRESULTS\nFive critically ill COVID-19 patients developed TAF in the period. All five patients had common risk conditions for TAF: central venous catheter at fungemia, previous exposure to broad-spectrum antibiotics, prior echinocandin therapy and previous prolonged corticosteroid therapy. The average time of intensive care unit hospitalisation previous to the TAF episode was 23 days. All but one patient had voriconazole therapy, and TAF 30-day mortality was 80%. The five T asahii strains from the COVID-19 patients belonged to 4 different haplotypes, mitigating the possibility of skin origin and cross-transmission linking the 5 reported episodes. The antifungal susceptibility testing revealed low minimal inhibitory concentrations for azole derivatives.\n\n\nCONCLUSIONS\nJudicious prescription of antibiotics, corticosteroids and antifungals needs to be discussed in critically ill COVID-19 patients to prevent infections by hard-to-treat fungi like T asahii.", "affiliations": "Universidade Federal de São Paulo, São Paulo, Brazil.;Hospital São Rafael, Salvador, Brazil.;Universidade Federal de São Paulo, São Paulo, Brazil.;Hospital São Rafael, Salvador, Brazil.;Hospital São Rafael, Salvador, Brazil.;Hospital São Rafael, Salvador, Brazil.;Universidade Federal de São Paulo, São Paulo, Brazil.", "authors": "Nobrega de Almeida|João|J|;Moreno|Lis|L|;Francisco|Elaine Cristina|EC|;Noronha Marques|Gabriela|G|;Mendes|Ana Verena|AV|;Barberino|Maria Goreth|MG|;Colombo|Arnaldo Lopes|AL|https://orcid.org/0000-0003-0793-8491", "chemical_list": "D000305:Adrenal Cortex Hormones; D000935:Antifungal Agents", "country": "Germany", "delete": false, "doi": "10.1111/myc.13333", "fulltext": null, "fulltext_license": null, "issn_linking": "0933-7407", "issue": "64(8)", "journal": "Mycoses", "keywords": "\nTrichosporon asahii\n; Brazil; COVID-19; fungemia", "medline_ta": "Mycoses", "mesh_terms": "D000305:Adrenal Cortex Hormones; D000368:Aged; D000935:Antifungal Agents; D001487:Basidiomycota; D001938:Brazil; D000086382:COVID-19; D058387:Candidemia; D005260:Female; D016469:Fungemia; D006239:Haplotypes; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010802:Phylogeny; D012307:Risk Factors; D015163:Superinfection; D060586:Trichosporonosis", "nlm_unique_id": "8805008", "other_id": null, "pages": "817-822", "pmc": null, "pmid": "34091966", "pubdate": "2021-08", "publication_types": "D016428:Journal Article", "references": null, "title": "Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids.", "title_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids" }

[ { "companynumb": "BR-AUROBINDO-AUR-APL-2021-042958", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "065498", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 pneumonia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN AND TAZOBACTAM" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ANIDULAFUNGIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Candida infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANIDULAFUNGIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Diabetes mellitus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN NOS" } ], "patientagegroup": null, "patientonsetage": "57", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Nobrega de Almeida J Jr, Moreno L, Francisco EC, Noronha Marques G, Mendes AV, Colombo AL et al.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids.. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211026", "receivedate": "20211026", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19998144, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220304" }, { "companynumb": "BR-AUROBINDO-AUR-APL-2021-042961", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "065498", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 pneumonia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN AND TAZOBACTAM" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ANIDULAFUNGIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Antifungal treatment", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANIDULAFUNGIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Diabetes mellitus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN NOS" } ], "patientagegroup": null, "patientonsetage": "73", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Nobrega de Almeida J Jr, Moreno L, Francisco EC, Noronha Marques G, Mendes AV, Colombo AL, et al.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids.. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211026", "receivedate": "20211026", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19992427, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "BR-MYLANLABS-2021M1070583", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "065458", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 pneumonia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ANIDULAFUNGIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Candida infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANIDULAFUNGIN" } ], "patientagegroup": null, "patientonsetage": "74", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200101" } }, "primarysource": { "literaturereference": "Nobrega de Almeida J Jr, Moreno L, Francisco EC, Noronha Marques G, Mendes AV, Barberino MG, et al. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses 2021;64(8):817-822.", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211007", "receivedate": "20211007", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19931167, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-PFIZER INC-2021739230", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "50684", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202008", "drugenddateformat": "610", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202007", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" } ], "patientagegroup": null, "patientonsetage": "72", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200801" } }, "primarysource": { "literaturereference": "Nobrega de Almeida, J.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211124", "receivedate": "20210625", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19461607, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-AUROBINDO-AUR-APL-2021-042959", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "065498", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 pneumonia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN AND TAZOBACTAM" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ANIDULAFUNGIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Candida infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANIDULAFUNGIN" } ], "patientagegroup": null, "patientonsetage": "74", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Nobrega de Almeida J Jr, Moreno L, Francisco EC, Noronha Marques G, Mendes AV, Barberino MG, et al.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids.. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211026", "receivedate": "20211026", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19992408, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "BR-MYLANLABS-2021M1070584", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "065458", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 pneumonia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ANIDULAFUNGIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Candida infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANIDULAFUNGIN" } ], "patientagegroup": null, "patientonsetage": "75", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200101" } }, "primarysource": { "literaturereference": "Nobrega de Almeida J Jr, Moreno L, Francisco EC, Noronha Marques G, Mendes AV, Barberino MG, et al. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses 2021;64(8):817-822.", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211008", "receivedate": "20211008", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19933128, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220304" }, { "companynumb": "BR-MYLANLABS-2021M1070581", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "065458", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 pneumonia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ANIDULAFUNGIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "2020", "drugenddateformat": "602", "drugindication": "Candida infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANIDULAFUNGIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Diabetes mellitus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN NOS" } ], "patientagegroup": null, "patientonsetage": "57", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200101" } }, "primarysource": { "literaturereference": "Nobrega de Almeida J Jr, Moreno L, Francisco EC, Noronha Marques G, Mendes AV, Barberino MG, et al. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses 2021;64(8):817-822.", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211007", "receivedate": "20211007", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19931169, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-PFIZER INC-2021739259", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "VORICONAZOLE" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "21266", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202007", "drugenddateformat": "610", "drugindication": "Trichosporon infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202007", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VORICONAZOLE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AMPHOTERICIN B" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202007", "drugenddateformat": "610", "drugindication": "Trichosporon infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202007", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMPHOTERICIN B" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202007", "drugenddateformat": "610", "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202006", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN AND TAZOBACTAM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE ACETATE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MG/KG, DAILY", "drugenddate": "202007", "drugenddateformat": "610", "drugindication": "COVID-19", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202006", "drugstartdateformat": "610", "drugstructuredosagenumb": "1", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE ACETATE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Diabetes mellitus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN NOS" } ], "patientagegroup": null, "patientonsetage": "73", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200701" } }, "primarysource": { "literaturereference": "Nobrega de Almeida, J.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211124", "receivedate": "20210624", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19459662, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-MYLANLABS-2021M1070585", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "065458", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 pneumonia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "ANIDULAFUNGIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "2020", "drugenddateformat": "602", "drugindication": "Antifungal prophylaxis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANIDULAFUNGIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Diabetes mellitus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN NOS" } ], "patientagegroup": null, "patientonsetage": "73", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200101" } }, "primarysource": { "literaturereference": "Nobrega de Almeida J Jr, Moreno L, Francisco EC, Noronha Marques G, Mendes AV, Barberino MG, et al. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses 2021;64(8):817-822.", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211008", "receivedate": "20211008", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19933122, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-PFIZER INC-2021739228", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "50684", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202007", "drugenddateformat": "610", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202006", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Diabetes mellitus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN NOS" } ], "patientagegroup": null, "patientonsetage": "73", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Systemic candida", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200701" } }, "primarysource": { "literaturereference": "Nobrega de Almeida, J.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211124", "receivedate": "20210625", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19461610, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-PFIZER INC-2021739229", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "50684", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202008", "drugenddateformat": "610", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202007", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Diabetes mellitus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN NOS" } ], "patientagegroup": null, "patientonsetage": "57", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Systemic candida", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200701" } }, "primarysource": { "literaturereference": "Nobrega de Almeida, J.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211124", "receivedate": "20210625", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19461620, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "BR-PFIZER INC-2021739183", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "50684", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202007", "drugenddateformat": "610", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202006", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" } ], "patientagegroup": null, "patientonsetage": "75", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Systemic candida", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200601" } }, "primarysource": { "literaturereference": "Nobrega de Almeida, J.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211124", "receivedate": "20210625", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19461595, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-AUROBINDO-AUR-APL-2021-042962", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "065498", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 pneumonia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN AND TAZOBACTAM" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ANIDULAFUNGIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Antifungal treatment", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANIDULAFUNGIN" } ], "patientagegroup": null, "patientonsetage": "72", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Nobrega de Almeida J Jr, Moreno L, Francisco EC, Noronha Marques G, Mendes AV, Colombo AL et al.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids.. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211026", "receivedate": "20211026", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19992435, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "BR-PFIZER INC-2021739258", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "VORICONAZOLE" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "21266", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202007", "drugenddateformat": "610", "drugindication": "Trichosporon infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202007", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VORICONAZOLE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AMPHOTERICIN B" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202007", "drugenddateformat": "610", "drugindication": "Trichosporon infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202007", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMPHOTERICIN B" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202007", "drugenddateformat": "610", "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202006", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN AND TAZOBACTAM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE ACETATE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MG/KG, DAILY", "drugenddate": "202007", "drugenddateformat": "610", "drugindication": "COVID-19", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202006", "drugstartdateformat": "610", "drugstructuredosagenumb": "1", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE ACETATE" } ], "patientagegroup": null, "patientonsetage": "75", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200701" } }, "primarysource": { "literaturereference": "Nobrega de Almeida, J.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211124", "receivedate": "20210624", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19459665, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-MYLANLABS-2021M1070586", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "065458", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 pneumonia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "ANIDULAFUNGIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "2020", "drugenddateformat": "602", "drugindication": "Antifungal prophylaxis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANIDULAFUNGIN" } ], "patientagegroup": null, "patientonsetage": "72", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200101" } }, "primarysource": { "literaturereference": "Nobrega de Almeida J Jr, Moreno L, Francisco EC, Noronha Marques G, Mendes AV, Barberino MG, et al. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses 2021;64(8):817-822.", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211008", "receivedate": "20211008", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19933121, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-PFIZER INC-2021739260", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "VORICONAZOLE" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "21266", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202008", "drugenddateformat": "610", "drugindication": "Trichosporon infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202008", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VORICONAZOLE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AMPHOTERICIN B" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202008", "drugenddateformat": "610", "drugindication": "Trichosporon infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202008", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMPHOTERICIN B" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202008", "drugenddateformat": "610", "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202007", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN AND TAZOBACTAM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE ACETATE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MG/KG, DAILY", "drugenddate": "202008", "drugenddateformat": "610", "drugindication": "COVID-19", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202007", "drugstartdateformat": "610", "drugstructuredosagenumb": "1", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE ACETATE" } ], "patientagegroup": null, "patientonsetage": "72", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200801" } }, "primarysource": { "literaturereference": "Nobrega de Almeida, J.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211124", "receivedate": "20210624", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19459663, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-PFIZER INC-2021739231", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "50684", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "202009", "drugenddateformat": "610", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "202008", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" } ], "patientagegroup": null, "patientonsetage": "74", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Systemic candida", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200901" } }, "primarysource": { "literaturereference": "Nobrega de Almeida, J.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211124", "receivedate": "20210625", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19461613, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "BR-AUROBINDO-AUR-APL-2021-042960", "fulfillexpeditecriteria": "1", "occurcountry": "BR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PIPERACILLIN SODIUM\\TAZOBACTAM SODIUM" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "065498", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 pneumonia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PIPERACILLIN AND TAZOBACTAM" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ANIDULAFUNGIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Candida infection", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANIDULAFUNGIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AMPHOTERICIN B" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Diarrhoea", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMPHOTERICIN B" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "VORICONAZOLE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Diarrhoea", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VORICONAZOLE" } ], "patientagegroup": null, "patientonsetage": "75", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Trichosporon infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fungaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Nobrega de Almeida J Jr, Moreno L, Francisco EC, Noronha Marques G, Mendes AV, Barberino MG, et al.. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids.. Mycoses. 2021;64(8):817-822", "literaturereference_normalized": "trichosporon asahii superinfections in critically ill covid 19 patients overexposed to antimicrobials and corticosteroids", "qualification": "3", "reportercountry": "BR" }, "primarysourcecountry": "BR", "receiptdate": "20211026", "receivedate": "20211026", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 19992413, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" } ]

{ "abstract": "Contrast-induced encephalopathy is a very rare complication associated with endovascular treatment of intracranial aneurysms. Patients with renal dysfunction may be prone to developing contrast medium neurotoxicity as a result of delayed elimination of the contrast medium in renal metabolism. This article focuses on our experience with contrast-induced encephalopathy in patients with end-stage renal disease requiring hemodialysis. The authors retrospectively reviewed five patients diagnosed with contrast-induced encephalopathy who underwent aneurysm coil embolization at their institution from January 2006 to December 2015. During the 10-year period, embolization was performed in 755 cases, among which contrast-induced encephalopathy occurred in five patients (0.66%). Three of the five patients were undergoing dialysis for chronic renal failure (one male and two female; mean age 66.7). Embolization for hemodialysis patients was performed in eight during the same period and the incidence of contrast-induced encephalopathy in hemodialysis patients is quite high in our series (3 of 8; 38%). Procedures were performed in one for recurrence of unruptured anterior-communicating artery aneurysm and in two for unruptured basilar-tip aneurysm. Mean approximately 220 ml of contrast media was used among three hemodialysis patients. All three patients showed an improvement or a control in symptoms soon after hemodialysis. Recovery of neurological symptoms was complete in two and almost normal in one within 1 week after intervention. Contrast-induced encephalopathy should be kept in mind as an expected complication of aneurysm embolization in hemodialysis patients. In hemodialysis patients with contrast-induced encephalopathy, performing hemodialysis is an effective treatment to improve symptoms early.", "affiliations": "Department of Neurosurgery, Nagoya University Graduate School of Medicine.;Department of Neurosurgery, Nagoya University Graduate School of Medicine.;Department of Neurosurgery, Nagoya University Graduate School of Medicine.;Department of Neurosurgery, Nagoya University Graduate School of Medicine.;Department of Neurosurgery, Nagoya University Graduate School of Medicine.", "authors": "Matsubara|Noriaki|N|;Izumi|Takashi|T|;Miyachi|Shigeru|S|;Ota|Keisuke|K|;Wakabayashi|Toshihiko|T|", "chemical_list": "D003287:Contrast Media", "country": "Japan", "delete": false, "doi": "10.2176/nmc.oa.2017-0132", "fulltext": "\n==== Front\nNeurol Med Chir (Tokyo)Neurol. Med. Chir. (Tokyo)NMCNeurologia medico-chirurgica0470-81051349-8029The Japan Neurosurgical Society 2909332610.2176/nmc.oa.2017-0132nmc_57-641Original ArticleContrast-induced Encephalopathy Following Embolization of Intracranial Aneurysms in Hemodialysis Patients MATSUBARA Noriaki 123IZUMI Takashi 1MIYACHI Shigeru 134OTA Keisuke 1WAKABAYASHI Toshihiko 11 Department of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan;2 Department of Neurosurgery, Chubu Rosai Hospital, Nagoya, Aichi, Japan;3 Department of Neurosurgery & Neuroendovascular Therapy, Osaka Medical College, Takatsuki, Osaka, Japan;4 Neuroendovascular Therapy Center, Aichi Medical University, Nagakute, Aichi, JapanAddress reprint requests to: Noriaki Matsubara, MD, Department of Neurosurgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. e-mail: mnoriaki0817@yahoo.co.jp12 2017 31 10 2017 57 12 641 648 08 6 2017 03 8 2017 © 2017 The Japan Neurosurgical Society2017This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/Contrast-induced encephalopathy is a very rare complication associated with endovascular treatment of intracranial aneurysms. Patients with renal dysfunction may be prone to developing contrast medium neurotoxicity as a result of delayed elimination of the contrast medium in renal metabolism. This article focuses on our experience with contrast-induced encephalopathy in patients with end-stage renal disease requiring hemodialysis. The authors retrospectively reviewed five patients diagnosed with contrast-induced encephalopathy who underwent aneurysm coil embolization at their institution from January 2006 to December 2015. During the 10-year period, embolization was performed in 755 cases, among which contrast-induced encephalopathy occurred in five patients (0.66%). Three of the five patients were undergoing dialysis for chronic renal failure (one male and two female; mean age 66.7). Embolization for hemodialysis patients was performed in eight during the same period and the incidence of contrast-induced encephalopathy in hemodialysis patients is quite high in our series (3 of 8; 38%). Procedures were performed in one for recurrence of unruptured anterior-communicating artery aneurysm and in two for unruptured basilar-tip aneurysm. Mean approximately 220 ml of contrast media was used among three hemodialysis patients. All three patients showed an improvement or a control in symptoms soon after hemodialysis. Recovery of neurological symptoms was complete in two and almost normal in one within 1 week after intervention. Contrast-induced encephalopathy should be kept in mind as an expected complication of aneurysm embolization in hemodialysis patients. In hemodialysis patients with contrast-induced encephalopathy, performing hemodialysis is an effective treatment to improve symptoms early.\n\ncontrast-induced encephalopathyembolizationintracranial aneurysmhemodialysisend-stage renal disease\n==== Body\nIntroduction\nContrast-induced encephalopathy is a very rare complication associated with endovascular treatment of intracranial aneurysms. The condition often arises in the occipital lobe with visual disturbance, but can also develop in other areas of the brain and, depending on the affected site, may cause various neurological abnormalities.1) While symptoms are often temporary and reversible, some reports have described cases in which permanent symptoms remained.1–3) It is thought that the mechanism involves the contrast medium passing through the blood-brain barrier and leaking into the brain tissue, thereby causing neurotoxicity.4,5) This report focuses on contrast-induced encephalopathy in hemodialysis patients.\n\nMaterials and Methods\nIn the present study, we retrospectively reviewed five patients diagnosed with contrast-induced encephalopathy who underwent intracranial aneurysm coil embolization including parent artery occlusion at our institution during the 10-year period from January 2006 to December 2015. We did not perform the intervention for the patients with markedly reduced kidney function to avoid precipitating end-stage renal disease induced by contrast medium but performed for those with chronic renal failure already maintained on regular hemodialysis. We usually tried to reduce the dose of contrast for the patients with moderate to severe renal insufficiency although we did not consider for hemodialysis patients. We used a nonionic iodinated contrast medium and routinely used iopamidol for intervention unless allergy or hypersensitivity for it in the patient. Imaging including control angiogram, rotational angiogram and angiogram in working projection) was performed with the contrast medium injected as an undiluted solution using an injector prior to insertion of the microcatheter and upon completion of embolization. During coil embolization, the contrast medium was diluted to approximately 2:1, and injection was manually performed. Patients diagnosed with contrast-induced encephalopathy were selected and examined from the clinical database in our department. Diagnosis of contrast-induced encephalopathy was made on the basis of postoperative neurological deteriorations and image findings in the computed tomography (CT)/magnetic resonance imaging (MRI) study excluding thromboembolic or hemorrhagic complications. We regarded cortical contrast enhancement and edematous change in affected site as characteristic image findings. Informed written consent was obtained from all the patients and/or their guardian(s).\n\nResults\nDuring the 10-year period, coil embolization was performed in 755 cases (694 with unruptured aneurysm and 61 with ruptured aneurysm), among which contrast-induced encephalopathy occurred in five patients (0.66%). The subject sample included two male and three female patients with a mean age of 64.2 years. All five patients underwent the intervention for unruptured intracranial aneurysm and incidence rate was 0.72% (5 of 694 patients with unruptured aneurysm). We carefully reviewed the clinical records, yet patients with ruptured intracranial aneurysm were not diagnosed as contrast-induced encephalopathy (it was not for sure but diagnosis might be difficult in ruptured aneurysms because of poor clinical condition and influence of subarachnoid hemorrhage in imaging). Contrast-induced encephalopathy was not observed after diagnostic angiogram for intracranial aneurysms during the same period. The aneurysm location was anterior circulation in two patients, and posterior circulation in three patients. All five patients had concurrent hypertension. The mean dose of contrast medium was approximately 250 ml. The contrast used was iopamidol in four patients, and iodixanol in one patient. Two of them without hemodialysis did not have severe renal dysfunction. Three of the five patients were undergoing dialysis for chronic renal failure (one male and two female; mean age 66.7).\n\nEmbolization for hemodialysis patients was performed in 8 (1 with ruptured and 7 with unruptured aneurysms) during the same period (8 of 755; 1.1% of embolization cases) and the incidence of contrast-induced encephalopathy in hemodialysis patients is 38% (3 of 8) in our series. Two of three had the history of polycystic kidney disease. Procedures were performed in one for recurrence of unruptured anterior communicating artery aneurysm and in two for unruptured basilar-tip aneurysm. Mean dose 220 ml of contrast media was used. They showed an improvement or a control in symptoms soon after hemodialysis. Recovery of neurological symptoms was complete in two and almost normal in one within 1 week after intervention. Contrast-induced encephalopathy in the hemodialysis and the non-hemodialysis patients were summarized in Table 1.\n\nRepresentative Cases\nCase 1\nThe case subject was a 63-year-old woman with an unruptured anterior communicating artery aneurysm. The patient had the medical history of polycystic kidney disease and hypertension. Hemodialysis initiated five years previously for chronic renal failure caused by polycystic kidney disease. An unruptured anterior communicating artery aneurysm was detected during screening for dementia. The subject had undergone the first coil embolization eight years ago (three years prior to the start of hemodialysis), and the second coil embolization four years ago (one year after the start of dialysis). However, on both occasions the subject progressed with no perioperative complications. In addition, three-dimensional CT angiography performed using contrast medium one month before this intervention did not indicate neurological symptoms. Hemodialysis was performed on the day prior to embolization. A guiding catheter was inserted into the left internal carotid artery and the left and right anterior cerebral arteries were delineated by left internal carotid angiogram. The size of aneurysm was approximately 6 mm (Figs. 1A and 1B). Stent-assisted coil embolization was performed, and the procedure was completed without any intraoperative complications (Fig. 1C). Iodixanol 270 mgI/ml (Visipaque 270; Daiichi Sankyo, Tokyo, Japan) was used as the contrast medium at a dose of approximately 210 ml. Immediately after treatment, partial paralysis was observed in the left limbs, with moderate paralysis observed in the left leg. Post-treatment CT revealed a high-density area along the sulcus of the bilateral frontal lobes (Figs. 1D and 1E). Diffusion-weighted image (DWI) of MRI performed 3 hrs after treatment revealed a faint hyper-intense area in the bilateral frontal lobe (Figs. 1F and 1G). The patient was treated with dexamethasone because we routinely used steroids postoperatively (6.6 mg twice a day). However, the day following intervention the paralysis in the left limbs progressed and became severe. Moreover, the patient experienced a generalized convulsion. Head CT performed 20 hrs after treatment revealed a residual high density area along the bilateral (dominantly right) frontal lobes with edematous changes (Figs. 1H and 1I). On the day following intervention, hemodialysis was performed as initially planned. After hemodialysis, the left-sided paralysis improved. The paralysis then improved further after performing hemodialysis a second time postoperatively day 3 after intervention. On day 7 after intervention, only mild paralysis of the left arm persisted, and the subject was discharged from hospital. The patient had neurological improvement after discharge and recovered to normal at one month follow-up in outpatient clinic.\n\nCase 2\nThe subject was a 74-year-old man with an unruptured basilar tip aneurysm. The patient had the medical history of diabetes, hypertension, liver cirrhosis and mitral insufficiency. Hemodialysis was initiated 10 years previously for chronic renal failure caused by diabetic nephropathy. The unruptured cerebral aneurysm was identified during brain health screening.\n\nHemodialysis was performed the day prior to embolization. A guiding catheter was placed into the left vertebral artery. The aneurysm was approximately 9 mm in size (Fig. 2A). Coiling of the aneurysm was performed using the double catheter technique and the procedure was completed without any intraoperative complications (Fig. 2B). Iopamidol 300 mgI/ml (Iopamiron; Bayer Yakuhin, Osaka, Japan) was used as the contrast medium at a dose of approximately 160 ml. Immediately after intervention the subject exhibited headache and vomiting, but there were no focal neurologic symptoms observed. The patient was treated with dexamethasone for postoperative routine use. However, several hours after intervention, the subject developed visual disturbance due to visual field defect, and mild disturbance of consciousness was observed. The day following intervention, the disturbance of consciousness progressed further. Head CT acquired the day after intervention revealed marked left side-dominant contrast medium residue in the bilateral occipital lobes and thalamus with edematous changes (Figs. 2C and 2D). At this point in time, contrast-induced encephalopathy was diagnosed, and hemodialysis was quickly performed. Immediately after dialysis, the disturbance of consciousness almost completely disappeared, but the visual disturbance remained. After performing dialysis on the second consecutive day after intervention, the visual disturbance almost entirely disappeared. MRI DWI acquired two-day after intervention revealed a hyper-intense area along the sulcus of the left occipital lobe, and faint hyper-intensity in the left thalamus (Figs. 2E and 2F). One week after intervention, the subject was discharged from hospital without sequelae.\n\nDiscussion\nPossible mechanism of contrast-induced encephalopathy\nContrast-induced encephalopathy is a very rare complication associated with the endovascular procedure, especially in cerebral angiogram, as well as other vessel angiograms. Although the detailed mechanism of contrast-induced encephalopathy is not understood, it is thought that the repeated injection of the contrast medium into the same vessel causes the blood-brain barrier to disrupt, resulting in leakage of the contrast medium into the brain tissue, which causes neurotoxicity and various neurological abnormalities.4,5)\n\nImage findings of contrast-induced encephalopathy\nTypical image findings in head CT performed immediately after treatment include enhancement effect in the cortical areas of the brain with edema. Findings in MRI have not been frequently reported. These include abnormal T2, fluid attenuated inversion recovery (FLAIR) and/or DWI hyper-intensities in the affected cortices although sometimes these lesions may be subtle.6) In this study, 8 except 1 patients with contrast-induced encephalopathy demonstrated typical image findings of CT, that was, cortical enhancement with edema. And remaining one presented abnormal findings in MRI because CT was skipped for detailed examination.\n\nContrast-induced encephalopathy and usage of contrast medium\nWhile one cause is thought to be higher osmolality of the contrast medium than the blood, contrast-induced encephalopathy also arises with the use of iodixanol, a low osmolality contrast medium with osmolality approximately that of physiological saline.7,8) Wilcox et al. reported that in an animal experiment, iodixanol and iopamidol exhibited the same ability to cross the blood-brain barrier.9) In the present study, contrast-induced encephalopathy occurred with the use of iodixanol in patient 1 and iopamidol in others. The osmolality of iopamidol to physiological saline was approximately 3:1. In terms of contrast medium used, while some reports describe the case with low doses,10) many suggest that event is associated with the injected dose of the contrast medium and the number of injections.11–13) Uchiyama et al. reported that blood-brain barrier dysfunction is affected by the injection of high concentrations, low temperatures and repeated injections with short interval into the same blood vessel.13) In this study, the mean dose of contrast medium was approximately 250 ml (mean 220 ml in hemodialysis and 285 ml in non-hemodialysis patients). Excessive use of contrast medium was one of the factors in the development of encephalopathy in our series.\n\nRisk factor of contrast-induced encephalopathy\nRisk factors for contrast-induced encephalopathy include hypertension and renal dysfunction.1,8,14) With regards to hypertension, it is thought that the blood-brain barrier is affected by a decline in blood vessels’ autoregulation. All of the patients that we treated had a history of hypertension and hypertensive encephalopathy was possibly one of the differential diagnoses.\n\nIt is possible that patients with renal dysfunction may be prone to developing contrast medium neurotoxicity as a result of delayed elimination of the contrast medium in renal metabolism. It also appears that because hemodialysis patients do not eliminate the contrast medium outside the body through the urine, toxicity from the contrast medium may be delayed. There are a few reports of contrast-induced encephalopathy in patients with dialysis and severe renal impairment8,15–21) although three out of five of the contrast-induced encephalopathy cases that we experienced were hemodialysis patients. In our limited number of series, the incidence of contrast-induced encephalopathy following embolization of intracranial aneurysm in hemodialysis patients is quite high. Embolization for the patients with severely reduced kidney function is usually avoided because of precipitating further deterioration of renal function induced by contrast medium although it would be performed for the patients already maintained on regular hemodialysis. Although severe renal failure is high risk for contrast-induced encephalopathy, it actually matters in hemodialysis patients.\n\nTreatment for contrast-induced encephalopathy\nTreatment for contrast-induced encephalopathy varies depending on the report, and remains controversial. As symptoms often improve in a few days with follow-up observation, conservative treatment is generally administered. Hydration and pharmacotherapy are commonly performed.1–3,6,10,11,21,22) Steroids are the most-used drug for pharmacotherapy. While steroids are used for the purpose of improving cerebral edema, their therapeutic effects are expected to be achieved through stabilizing the blood-brain barrier. Because we routinely use steroid after coil embolization for several days and therefore, steroids were administered for all five patients with contrast-induced encephalopathy. Mannitol is another type of drug used to treat the condition.1,10,14,22) Mannitol is a hyperosmotic diuretic and used for the purpose of improving cerebral edema although we did not use mannitol in this series. However, the effect is limited among the hemodialysis patients because of anuria/oliguria from renal impairment. Mannitol opens the blood-brain barrier but it could conversely induce contrast medium into the brain tissue due to delayed metabolism. The use of mannitol just during hemodialysis is worth considering but is not recommended in the daily use for contrast-induced encephalopathy.\n\nHemodialysis and contrast-induced encephalopathy\nThe half-life of contrast medium in the blood of patients with normal renal function is approximately 2 hrs. In patients with severe renal dysfunction, however, it is approximately more than 16 hrs.23,24) In hemodialysis patients, it is more prolonged. In this series, cortical enhancement with edematous changes was still remained even one day after intervention (cases 1, 2). It would be better to limit the dose of contrast medium during intervention in hemodialysis patients. Hemodialysis is useful for the removal of the contrast medium from the blood, with approximately 80% of the contrast medium having been removed within 4 hrs.23,24) In past case reports of contrast-induced encephalopathy, including patients undergoing hemodialysis and those with severe renal dysfunction, there have been cases where symptoms were improved by hemodialysis.8,19) All of three of our patients showed an improvement or a control in symptoms after hemodialysis. Hemodialysis excretes the contrast medium and lowers the serum concentration. Therefore, the contrast medium leaked into the brain tissue is transferred to the blood, resulting in recovery from neurotoxicity. Dialysis disequilibrium syndrome is a rare but serious complication of hemodialysis25) and pathophysiology concerning this syndrome should be kept in mind. It presents neurological symptoms caused by cerebral edema attributed to an osmotic gradient between the brain and the blood as a result of rapid removal of urea by hemodialysis. Phenomenon like this syndrome could deteriorate cerebral edema due to contrast-induced encephalopathy by performing hemodialysis.\n\nWhile the effectiveness of hemodialysis for the prevention and treatment of contrast-induced nephropathy has not been proved,23,26) hemodialysis is an effective treatment method for contrast-induced encephalopathy in patients with severe renal dysfunction. Contrast-induced encephalopathy could present with severe neurological symptoms and permanent neurological symptoms could remain and hemodialysis should be considered as it can work to quickly remove the contrast medium in the blood.\n\nConclusion\nWe experienced three hemodialysis patients for contrast-induced encephalopathy, and found that the neurological symptoms improved after hemodialysis. Contrast-induced encephalopathy should be kept in mind as an expected complication of aneurysm embolization in hemodialysis patients. In hemodialysis patients with contrast-induced encephalopathy, performing hemodialysis is an effective treatment to improve symptoms early.\n\nConflicts of Interest Disclosure\n\nThe authors have no personal, financial interest in any of the materials or devices described in this article.\n\nAcknowledgement\nThe author would like to thank Takumi Asai, MD and Kazunori Shintai, MD (Nagoya Medical Center), Takashi Yamanouchi, MD (Tosei General Hospital), Hayato Tajima, MD (Handa City Hospital), Tasuku Imai, MD, Masashi Ito, MD and Masahiro Nishihori, MD (Nagoya University Graduate School of Medicine), for their generous support in this study.\n\nFig. 1 Case 1. Left internal carotid angiogram demonstrating recurrence of anterior communicating artery aneurysm (A: three-dimensional reconstruction angiogram and B: conventional angiogram). C: Angiogram acquired after embolization by a stent-assisted technique showing complete occlusion of the aneurysm. D and E: Non-contrast head CT acquired immediately after embolization revealed a cortical contrast enhancement along the sulcus of the bilateral frontal lobes. F and G: Diffusion-weighted image of MRI performed 3 hrs after treatment showing a faint hyper-intense area in the bilateral frontal lobes. H and I: Non contrast CT performed 20 hrs after treatment demonstrating a residual cortical enhancement in the bilateral frontal lobes with edematous changes.\n\nFig. 2 Case 2. A: Left vertebral angiogram demonstrating an unruptured basilar tip aneurysm. B: Angiogram acquired after embolization by a double catheter technique showing complete occlusion of the aneurysm. C and D: Non-contrast head CT acquired the day after embolization showing a residual cortical enhancement in the bilateral occipital lobes and left thalamus with edematous changes. E and F: Diffusion-weighted image of MRI performed 2 days after treatment showing a hyper-intensity along the sulcus of the left occipital lobe, and faint hyper-intensity in the left thalamus.\n\nTable 1 Cases of contrast-induced encephalopathy in hemodialysis and non-hemodialysis patients\n\nCase no.\tAge\tSex\tCause of renal failure and hemodialysis\tDuration of hemodialysis (year)\tStage of CKD\tPast history\tPrevious intervention or angiogram\tSite of aneurysm (ruptured or unruptured, right or left)\tSize of aneurysm (mm)\tEndovascular procedure\tType of contrast\tDose of contrast (ml)\tSite of guiding catherter\tClinical symptom\tRegion involved\tFirst hemodialysis after intervention\tClinical improvement after hemodyalysis\tmRS at discharge\tmRS at final follow-up\t\nHemodialysis patients\t\n1\t63\tF\tPolycystic kidney\t5\t5\tHypertension\tCoil embolization (twice) (4-year and 8-year previously)\tAnterior communicating artery\nUnruptured\t6\tStent-assisted coiling\tIodixanol (Visipaque270)\t210\tInternal carotid arery (Left)\tHemiparesis\nConvulsion\tFrontal lobe (Bilateral)\tNext day\tYes\t1\t0\t\n2\t74\tM\tDiabetes mellitus\t10\t5\tHypertension\nLiver cirrhosis\nMitral insufficiency\tNone\tBasilar-tip\nUnruptured\t9\tCoiling with double catheters\tIopamidol (Iopamilon300)\t160\tVertebral artery (Left)\tBlindness\nConsciousness disturbance\tOccipital lobe (Bilateral)\nThalamus (Left)\tNext day\tYes\t0\t0\t\n3\t63\tF\tPolycystic kidney\t4\t5\tHypertension\nAngina\nGastric ulcer\tNone\tBasilar-tip\nUnruptured\t12\tBalloon-assisted coiling\tIopamidol (Iopamilon300)\t300\tVertebral artery (Left)\tBlindness\tOccipital lobe (Bilateral)\tSame day\tYes\t0\t0\t\n\t\nNon-hemodyalysis patients\t\n4\t70\tF\tNA\tNA\t2 (eGFR 67.0)\tHypertension\tNone\tPosterior cerebral artery (P2)\nUnruptured, Left\t11\tStent-assisted coiling\tIopamidol (Iopamilon300)\t270\tInternal carotid artery (Left)\tBlindness\nHemiparesis\nAgnosia\tFrontal (Left), Parietal (Left), and Occipital lobe (Left)\tNA\tNA\t1\t0\t\n5\t51\tF\tNA\tNA\t2 (eGFR 79.7)\tHypertension\tCoil embolization 1-year previously\tInternal carotid artery (C4)\nUnruptured, Left\t8\tStent-assisted coiling\tIopamidol (Iopamilon300)\t300\tInternal carotid artery (Left)\tHemiparesis\nAphasia\nConsciousness disturbance\tFrontal lobe (Left)\nParietal lobe (Left)\tNA\tNA\t0\t0\t\nCKD: chronic kidney disease, eGFR: estimated glomerular filtration rate, NA: not applicable.\n==== Refs\nReferences\n1) Leong S Fanning NF : Persistent neurological deficit from iodinated contrast encephalopathy following intracranial aneurysm coiling. A case report and review of the literature . Interv Neuroradiol \n18 : 33 –41 , 2012 22440599 \n2) Niimi Y Kupersmith MJ Ahmad S Song J Berenstein A : Cortical blindness, transient and otherwise, associated with detachable coil embolization of intracranial aneurysms . AJNR Am J Neuroradiol \n29 : 603 –607 , 2008 18065506 \n3) Shinoda J Ajimi Y Yamada M Onozuka S : Cortical blindness during coil embolization of an unruptured intracranial aneurysm—case report . Neurol Med Chir (Tokyo) \n44 : 416 –419 , 2004 15508349 \n4) Lalli AF : Contrast media reactions: data analysis and hypothesis . Radiology \n134 : 1 –12 , 1980 6985735 \n5) Uchiyama Y Abe T Hirohata M : Blood brain-barrier disruption of nonionic iodinated contrast medium following coil embolization of a ruptured intracerebral aneurysm . AJNR Am J Neuroradiol \n25 : 1783 –1786 , 2004 15569746 \n6) Saigal G Bhatia R Bhatia S Wakhloo AK : MR findings of cortical blindness following cerebral angiography: is this entity related to posterior reversible leukoencephalopathy? \nAJNR Am J Neuroradiol \n25 : 252 –256 , 2004 14970026 \n7) Lee KK Kang DH Kim YS Park J : Serious blood-brain barrier disruption after coil embolization of unruptured intracranial aneurysm: report of two cases and role of immediate postembolization ct scan . J Korean Neurosurg Soc \n50 : 45 –47 , 2011 21892404 \n8) Yan J Ramanathan V : Severe encephalopathy following cerebral arteriogram in a patient with end-stage renal disease . Semin Dial \n26 : 203 –207 , 2013 23406363 \n9) Wilcox J Wilson AJ Evill CA Sage MR : A comparison of blood-brain barrier disruption by intracarotid iohexol and iodixanol in the rabbit . AJNR Am J Neuroradiol \n8 : 769 –772 , 1987 2823587 \n10) Potsi S Chourmouzi D Moumtzouoglou A Nikiforaki A Gkouvas K Drevelegas A : Transient contrast encephalopathy after carotid angiography mimicking diffuse subarachnoid haemorrhage . Neurol Sci \n33 : 445 –448 , 2012 21927883 \n11) Iwata T Mori T Tajiri H Miyazaki Y Nakazaki M : Repeated injection of contrast medium inducing dysfunction of the blood-brain barrier: case report . Neurol Med Chir (Tokyo) \n53 : 34 –36 , 2013 23358167 \n12) Kuhn MJ Burk TJ Powell FC : Unilateral cerebral cortical and basal ganglia enhancement following overdosage of nonionic contrast media . Comput Med Imaging Graph \n19 : 307 –311 , 1995 7641175 \n13) Uchiyama Y Abe T Tanaka N : Factors contributing to blood-brain barrier disruption following intracarotid injection of nonionic iodinated contrast medium for cerebral angiography: experimental study in rabbits . Radiat Med \n24 : 321 –326 , 2006 16958409 \n14) Guimaraens L Vivas E Fonnegra A : Transient encephalopathy from angiographic contrast: a rare complication in neurointerventional procedures . Cardiovasc Intervent Radiol \n33 : 383 –388 , 2010 19504154 \n15) Chen CW Lin CJ Guo WY Liang IP : Mimicker of subarachnoid hemorrhage in a hemodialysis patient . Kidney Int \n82 : 940 , 2012 23018836 \n16) García de Lara J Vázquez-Rodríguez JM Salgado-Fernández J Calviño-Santos R Vázquez-González N Castro-Beiras A : [Transient cortical blindness following cardiac catheterization: an alarming but infrequent complication with a good prognosis] . Rev Esp Cardiol \n61 : 88 –90 , 2008 18221698 \n17) Gellen B Remp T Mayer T Milz P Franz WM : Cortical blindness: a rare but dramatic complication following coronary angiography . Cardiology \n99 : 57 –59 , 2003 12589125 \n18) Merchut MP Richie B : Transient visuospatial disorder from angiographic contrast . Arch Neurol \n59 : 851 –854 , 2002 12020271 \n19) Muruve DA Steinman TI : Contrast-induced encephalopathy and seizures in a patient with chronic renal insufficiency . Clin Nephrol \n45 : 406 –409 , 1996 8793235 \n20) Ozelsancak R Erken E Yildiz I Giray S Yildirim T Micozkadioglu H : A very rare case of encephalopathy in a patient with end-stage renal disease: contrast agent, ioversol . Ren Fail \n32 : 1128 –1130 , 2010 20863223 \n21) Studdard WE Davis DO Young SW : Cortical blindness after cerebral angiography. Case report . J Neurosurg \n54 : 240 –244 , 1981 7452339 \n22) Lantos G : Cortical blindness due to osmotic disruption of the blood-brain barrier by angiographic contrast material: CT and MRI studies . Neurology \n39 : 567 –571 , 1989 2927682 \n23) Deray G : Dialysis and iodinated contrast media . Kidney Int Suppl \n69 : S25 –S29 , 2006 \n24) Lorusso V Taroni P Alvino S Spinazzi A : Pharmacokinetics and safety of iomeprol in healthy volunteers and in patients with renal impairment or end-stage renal disease requiring hemodialysis . Invest Radiol \n36 : 309 –316 , 2001 11410750 \n25) Zepeda-Orozco D Quigley R : Dialysis disequilibrium syndrome . Pediatr Nephrol \n27 : 2205 –2211 , 2012 22710692 \n26) Morcos SK Thomsen HS Webb JA Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) : Dialysis and contrast media . Eur Radiol \n12 : 3026 –3030 , 2002 12439587\n\n", "fulltext_license": "CC BY-NC-ND", "issn_linking": "0470-8105", "issue": "57(12)", "journal": "Neurologia medico-chirurgica", "keywords": "contrast-induced encephalopathy; embolization; end-stage renal disease; hemodialysis; intracranial aneurysm", "medline_ta": "Neurol Med Chir (Tokyo)", "mesh_terms": "D000368:Aged; D001927:Brain Diseases; D003287:Contrast Media; D004621:Embolization, Therapeutic; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm; D007676:Kidney Failure, Chronic; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012189:Retrospective Studies", "nlm_unique_id": "0400775", "other_id": null, "pages": "641-648", "pmc": null, "pmid": "29093326", "pubdate": "2017-12-15", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "16612397;7452339;16958409;14970026;7641175;22440599;23018836;2927682;20863223;18221698;23406363;15508349;15569746;22710692;2823587;12589125;12020271;11410750;6985735;21892404;21927883;8793235;23358167;12439587;18065506;19504154", "title": "Contrast-induced Encephalopathy Following Embolization of Intracranial Aneurysms in Hemodialysis Patients.", "title_normalized": "contrast induced encephalopathy following embolization of intracranial aneurysms in hemodialysis patients" }

[ { "companynumb": "JP-BRACCO DIAGNOSTICS, INC.-2018JP00071", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "IOPAMIDOL" }, "drugadditional": null, "drugadministrationroute": "013", "drugauthorizationnumb": "018735", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": "300", "drugcumulativedosageunit": "012", "drugdosageform": "INJECTION", "drugdosagetext": "300 ML, SINGLE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANGIOGRAM", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOPAMIDOL" } ], "patientagegroup": null, "patientonsetage": "51", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hemiparesis", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Extra dose administered", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Contrast encephalopathy", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "MATSUBARA N, IZUMI T, MIYACHI S, OTA K, WAKABAYASHI T. CONTRAST-INDUCED ENCEPHALOPATHY FOLLOWING EMBOLIZATION OF INTRACRANIAL ANEURYSMS IN HEMODIALYSIS PATIENTS. NEUROL MED CHIR (TOKYO) 2017? 57: 641-648.", "literaturereference_normalized": "contrast induced encephalopathy following embolization of intracranial aneurysms in hemodialysis patients", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20180116", "receivedate": "20180116", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14392349, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "JP-BRACCO-2018JP00068", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "IOPAMIDOL" }, "drugadditional": null, "drugadministrationroute": "013", "drugauthorizationnumb": "018735", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": "270", "drugcumulativedosageunit": "012", "drugdosageform": "INJECTION", "drugdosagetext": "270 ML, SINGLE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANGIOGRAM", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "270", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOPAMIDOL" } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Contrast encephalopathy", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Extra dose administered", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "MATSUBARA N, IZUMI T, MIYACHI S, OTA K, WAKABAYASHI T. CONTRAST-INDUCED ENCEPHALOPATHY FOLLOWING EMBOLIZATION OF INTRACRANIAL ANEURYSMS IN HEMODIALYSIS PATIENTS. NEUROL MED CHIR (TOKYO) 2017? 57: 641-648.", "literaturereference_normalized": "contrast induced encephalopathy following embolization of intracranial aneurysms in hemodialysis patients", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20180116", "receivedate": "20180116", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14392410, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "JP-BRACCO DIAGNOSTICS, INC.-2018JP00072", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "IOPAMIDOL" }, "drugadditional": null, "drugadministrationroute": "013", "drugauthorizationnumb": "018735", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": "300", "drugcumulativedosageunit": "012", "drugdosageform": "INJECTION", "drugdosagetext": "300 ML, SINGLE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANGIOGRAM", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOPAMIDOL" } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Extra dose administered", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Contrast encephalopathy", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "MATSUBARA N, IZUMI T, MIYACHI S, OTA K, WAKABAYASHI T. CONTRAST-INDUCED ENCEPHALOPATHY FOLLOWING EMBOLIZATION OF INTRACRANIAL ANEURYSMS IN HEMODIALYSIS PATIENTS. NEUROL MED CHIR (TOKYO) 2017? 57: 641-648.", "literaturereference_normalized": "contrast induced encephalopathy following embolization of intracranial aneurysms in hemodialysis patients", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20180116", "receivedate": "20180116", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14392351, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "JP-BRACCO-2018JP00043", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "IOPAMIDOL" }, "drugadditional": null, "drugadministrationroute": "013", "drugauthorizationnumb": "018735", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": "160", "drugcumulativedosageunit": "012", "drugdosageform": "INJECTION", "drugdosagetext": "160 ML, SINGLE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANGIOGRAM", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "160", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IOPAMIRON" } ], "patientagegroup": null, "patientonsetage": "74", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Extra dose administered", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Contrast encephalopathy", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "MATSUBARA N, IZUMI T, MIYACHI S, OTA KEISUKE, WAKABAYASHI T. CONTRAST-INDUCED ENCEPHALOPATHY FOLLOWING EMBOLIZATION OF INTRACRANIAL ANEURYSMS IN HEMODIALYSIS PATIENTS. NEUROL MED CHIR (TOKYO) 2017? 57: 641-648.", "literaturereference_normalized": "contrast induced encephalopathy following embolization of intracranial aneurysms in hemodialysis patients", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20180117", "receivedate": "20180117", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14401893, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" } ]

{ "abstract": "We report a case of IgA vasculitis that developed during the treatment of tuberculosis. Patients with tuberculosis who are on antituberculosis treatment can be administered steroids for severe disease or complications.", "affiliations": "Department of Gastroenterology Akashi City Hospital Akashi Japan.;Department of Nephrology Akashi City Hospital Akashi Japan.;Department of Gastroenterology Akashi City Hospital Akashi Japan.;Department of Gastroenterology Akashi City Hospital Akashi Japan.;Department of Gastroenterology Akashi City Hospital Akashi Japan.;Department of Gastroenterology Akashi City Hospital Akashi Japan.;Department of Gastroenterology Akashi City Hospital Akashi Japan.;Department of Gastroenterology Akashi City Hospital Akashi Japan.;Department of Gastroenterology Akashi City Hospital Akashi Japan.;Department of Gastroenterology Akashi City Hospital Akashi Japan.", "authors": "Yamauchi|Norihito|N|https://orcid.org/0000-0002-7186-8611;Tanda|Shuji|S|;Kashiwagi|Saori|S|;Ohnishi|Atsunori|A|;Kugai|Munehiro|M|;Akazawa|Takako|T|;Matsumoto|Tsuguhiro|T|;Yamauchi|Junko|J|;Muramatsu|Akira|A|;Fujimoto|Soutaro|S|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1002/ccr3.2938", "fulltext": "\n==== Front\nClin Case Rep\nClin Case Rep\n10.1002/(ISSN)2050-0904\nCCR3\nClinical Case Reports\n2050-0904 John Wiley and Sons Inc. Hoboken \n\n10.1002/ccr3.2938\nCCR32938\nCase Report\nCase Reports\nFatal gastrointestinal bleeding due to IgA vasculitis complicated with tuberculous lymphadenitis: A case report and literature review\nYAMAUCHI et al.Yamauchi Norihito https://orcid.org/0000-0002-7186-8611\n1\nn.yamauti@akashi-shiminhosp.jp Tanda Shuji \n2\n Kashiwagi Saori \n1\n Ohnishi Atsunori \n1\n Kugai Munehiro \n1\n Akazawa Takako \n1\n Matsumoto Tsuguhiro \n1\n Yamauchi Junko \n1\n Muramatsu Akira \n1\n Fujimoto Soutaro \n1\n \n1 \nDepartment of Gastroenterology\nAkashi City Hospital\nAkashi\nJapan\n\n\n2 \nDepartment of Nephrology\nAkashi City Hospital\nAkashi\nJapan\n\n* Correspondence\n\nNorihito Yamauchi, Department of Gastroenterology, Akashi City Hospital, 1‐33 Takashōmachi, Akashi, Hyogo 673‐8501, Japan.\n\nEmail: n.yamauti@akashi-shiminhosp.jp\n\n06 7 2020 \n9 2020 \n8 9 10.1002/ccr3.v8.91741 1747\n16 11 2019 28 3 2020 25 4 2020 © 2020 The Authors. Clinical Case Reports published by John Wiley & Sons LtdThis is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Abstract\nWe report a case of IgA vasculitis that developed during the treatment of tuberculosis. Patients with tuberculosis who are on antituberculosis treatment can be administered steroids for severe disease or complications.\n\nWe report a case of IgA vasculitis that developed during the treatment of tuberculosis. Patients with tuberculosis who are on antituberculosis treatment can be administered steroids for severe disease or complications.\n\n\n\ngastrointestinal bleedingHenoch‐Schönlein purpuraIgA vasculitisleukocytoclastic vasculitistuberculosis source-schema-version-number2.0cover-dateSeptember 2020details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:5.9.1 mode:remove_FC converted:17.09.2020\n\n\nYamauchi \nN \n, \nTanda \nS \n, \nKashiwagi \nS \n, et al. Fatal gastrointestinal bleeding due to IgA vasculitis complicated with tuberculous lymphadenitis: A case report and literature review\n. Clin Case Rep . 2020 ;8 :1741 –1747\n. 10.1002/ccr3.2938\n==== Body\n1 INTRODUCTION\nImmunoglobulin A vasculitis (IgAV), formerly called Henoch‐Schönlein purpura, is a small vessel vasculitis that commonly occurs in children but can also affect people of all ages. Patients with this condition typically exhibit lower extremity purpura, arthritis, and hematuria. The gastrointestinal tract is affected in approximately one‐half of patients with IgAV. Gastrointestinal symptoms include abdominal pain, nausea, vomiting, and occult or overt intestinal bleeding. The condition is generally self‐limiting, and patients are usually managed with symptomatic treatment, but there are also severe cases with gastrointestinal bleeding, intussusception, infarction, and perforation.\n1\n, \n2\n, \n3\n Although various infectious and chemical triggers are recognized, the underlying cause of IgAV remains unknown to date.\n4\n\n\n\nWe report the case of a patient with IgAV that developed during treatment of tuberculous lymphadenitis and later proved fatal because of deterioration of gastrointestinal lesions.\n\n2 CASE REPORT\nA 71‐year‐old man with diabetes mellitus presented to our institution complaining of left axillary lymphadenopathy, which lasted for 1 month. Whole‐body CT revealed lymphadenopathy with central necrosis in the left clavicle, axilla, and abdomen. Scars and nonspecific fibrosis were observed in the apex of both lungs, but no active lesions or tumors were found in the lungs or other organs. Mycobacterium tuberculosis was detected from the exudate of the left axillary lymph nodes but not from the sputum, and tuberculous lymphadenitis diagnosis was made. Thereafter, the patient was treated with isoniazid (300 mg), rifampicin (450 mg), pyrazinamide (1.5 g), and ethambutol (1 g) daily. On the 19th day of treatment, he complained of abdominal pain and diarrhea, and on day 20, palpable purpura appeared on both of his legs (Figure 1A). Laboratory findings were as follows: white blood cell count, 11.3 × 103/μL; eosinophils, 0.2%; hemoglobin level, 13.2 g/dL; platelet count, 498 × 103/μL; international normalized ratio, 1.05; D‐dimer, 61.9 μg/mL; percentage factor XIII activity, 77%; serum urea level, 20.9 mg/dL; creatinine level, 0.55 mg/dL; C‐reactive protein level, 12.5 mg/dL; serum, IgA 472 mg/dL; IgE, 122 IU/mL. Meanwhile, the results of serologic tests for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, and hepatitis B and C viruses were all negative. Urinalysis showed a protein level of 50 mg/dL, and the patient tested negative for occult blood. Abdominal computed tomography showed wall thickening of the duodenum and small intestine, and mild to moderate ascites (Figure 2). An endoscopic examination demonstrated highly reddish erosions in the antrum of the stomach (Figure 3A) and circular ulcers in the descending part of the duodenum (Figure 3B). Biopsy of skin lesions showed leukocytoclastic vasculitis (Figure 1B). The deposition of IgA on the vascular wall was not proven, and we reached a diagnosis of IgAV in combination with palpable purpura and digestive symptoms.\n\nFigure 1 A, Palpable purpura developed on the lower extremities. B, Biopsy of skin lesions shows leukocytoclastic vasculitis with neutrophilic infiltration of small vessels in the superficial dermis. (Hematoxylin and eosin, ×400)\n\nFigure 2 Abdominal computed tomography shows wall thickening of the duodenum and small intestine, and mild to moderate ascites\n\nFigure 3 Upper gastrointestinal endoscopy shows highly reddish erosions in the antrum of the stomach (A) and circular ulcers with irregularly shaped margin in the descending duodenum (B)\n\nThe clinical course is shown in Figure 4. We considered corticosteroid administration to improve his abdominal symptoms, but we believed that this also carried a risk of worsening of tuberculosis and diabetes, so we opted to manage the patient with fasting and rest instead. A small amount of bloody stool was noted on day 27, but upper and lower gastrointestinal endoscopy did not reveal a definite source of bleeding. On day 30, the patient suffered hypovolemic shock as a result of massive blood loss, and we started systemic management, blood transfusion, and venous corticosteroid administration. Simultaneously, acute respiratory distress syndrome caused by aspiration pneumonia, and acute kidney injury occurred, which indicated that the patient required artificial respiration and hemodialysis. Hemorrhage was relieved temporarily, but a large amount of bloody stool reappeared on day 50, making it impossible to manage his condition by conservative treatment. Although we considered performing abdominal surgery, his general condition was deemed too severe for this approach. Therefore, abdominal angiography was performed with sufficient informed consent. Because the extravasation of contrast agent was observed in the jejunum, we performed transcatheter arterial embolization. Consequently, blood loss decreased, but gastrointestinal perforation merged. The patient died on day 56. His relatives did not accept the autopsy.\n\nFigure 4 Clinical course after tuberculosis treatment was initiated. †Units of red cell concentrate used for blood transfusion. AKI, acute kidney injury; ARDS, acute respiratory distress syndrome; Cr, creatinine; EB, ethambutol; Hb, hemoglobin; HD, hemodialysis; INH, isoniazid; mPSL, methylprednisolone; PSL, prednisolone; PZA, pyrazinamide; RFP, rifampicin; TAE, transcatheter arterial embolization.\n\n3 DISCUSSION\nWe report a patient who developed leukocytoclastic vasculitis during mycobacterial infection treatment. Leukocytoclastic vasculitis is a term for pathological finding, and several vasculitides show this finding. Among these vasculitides, IgAV was defined as vasculitis with IgA1‐dominant immune deposits that invades small blood vessels in the skin and gastrointestinal tract and often cause arthritis.\n5\n However, IgA deposition cannot be proven in all cases, and some cases are difficult to diagnose.\n2\n In the present case, there was no opportunity to prove IgA deposition. Biopsies from the gastric and duodenal mucosa did not contain appropriately sized blood vessels, and the involvement of vasculitis could not be pointed out. Therefore, we made the diagnosis of IgAV from clinical symptoms (ie, palpable purpura and abdominal pain) on the basis of the conventional criteria for Henoch‐Schönlein purpura proposed by the American College of Rheumatology (ACR) and the European League Against Rheumatism, Pediatric Rheumatology International Trials Organization, and Pediatric Rheumatology European Society (EULAR/PRINTO/PRES).\n6\n, \n7\n, \n8\n\n\n\nThe pathogenesis of IgAV is not yet clear, although several factors—such as infectious agents, dietary allergens, vaccines, and drugs—are presumed to be potential immunologic triggers. Tuberculosis has also been reported as an infectious agent associated with IgAV.\n4\n The mechanism by which tuberculosis causes IgAV is unknown. Cutaneous vasculitis associated with tuberculosis is speculated to be caused by: (a) direct invasion of the vessel wall by tubercle bacilli; (b) immunological reaction involving the deposition of immune complexes; (c) intravascular release of mycobacteria followed by an Arthus reaction and delayed hypersensitivity response; or (d) rifampicin‐dependent antibody and immune complex formation.\n9\n\n\n\nWe searched for relevant English and Japanese articles in PubMed using the following keywords: IgA vasculitis, Henoch‐Schönlein purpura or leukocytoclastic vasculitis, and tuberculosis. Twenty‐six cases considered as IgAV met the classification criteria set by the ACR or the EULAR/PRINT/PRES\n9\n, \n10\n, \n11\n, \n12\n, \n13\n, \n14\n, \n15\n, \n16\n, \n17\n, \n18\n, \n19\n, \n20\n, \n21\n, \n22\n, \n23\n, \n24\n, \n25\n, \n26\n, \n27\n, \n28\n, \n29\n; these consisted of 14 cases before the treatment of tuberculosis (pretreatment group) and 12 cases after the treatment of tuberculosis (post‐treatment group) (Tables 1 and 2). The overall median age of patients was 37 years, and 19 (73.1%) of them were male. Gastrointestinal symptoms occurred in 5 (35.7%) of pretreatment patients and in 4 (33.3%) of post‐treatment patients. In the pretreatment group, tuberculosis treatment was performed in 10 cases (71.4%), and only 1 case was treated with steroids. In the post‐treatment group, antituberculous drugs were discontinued in 8 cases (66.7%), and steroids were administered in 7 cases (58.3%). In both groups, there was a single case of death, both of which were caused by exacerbation of the underlying disease, and the present case marks the first report of death caused by deterioration of digestive tract lesions. Because IgAV is thought to be caused by the immune response, the treatment of removing allergens is appropriate. Therefore, it is reasonable to start tuberculosis treatment for pretreatment patients and to cease treatment with antituberculosis drugs for post‐treatment patients. In the present case, cessation of treatment with antituberculosis drugs was considered, but because of concerns that this could lead to worsening of tuberculosis, we decided to continue with the treatment.\n\nTable 1 Characteristics and outcomes in patients with IgA vasculitis complicated with tuberculosis (Onset before tuberculosis treatment)\n\nReference\tAge (year)\tSex\tType of tuberculosis\tRenal symptoms\tArthralgia/arthritis\tGastrointestinal symptoms\tLCV\tIgA deposit\na\n\n\tTreatment\tOutcome\t\nDalgleish and Ansell\t44\tM\tPulmonary tuberculosis\t+\t−\t+\tNR\tNR\tSupportive therapy\tSurvive\t\n\t31\tF\tPulmonary tuberculosis\t+\t−\t+\tNR\tNR\tSupportive therapy\tDeath\t\n\t47\tM\tPulmonary tuberculosis\t−\t+\t−\tNR\tNR\tSupportive therapy\tSurvive\t\nWashio et al\t21\tM\tTuberculous pleurisy\t+\t−\t−\tNR\t+\tTuberculosis treatment\tSurvive\t\nSais et al\t61\tF\tTuberculous lymphadenitis\t−\t−\t−\t+\t+\tTuberculosis treatment, Colchicine\tSurvive\t\nLee et al\t15\tF\tPulmonary tuberculosis\t−\t+\t−\t+\tNR\tTuberculosis treatment\tSurvive\t\n\t13\tF\tPositive for blood mononuclear cell PCR\t−\t−\t+\t+\tNR\tTuberculosis treatment\tSurvive\t\nMinguez et al\t36\tM\tPulmonary tuberculosis, Tuberculous pleurisy\t−\t+\t−\t+\tNR\tTuberculosis treatment, NSAIDs\tSurvive\t\nIslek et al\t8\tF\tPulmonary tuberculosis\t−\t−\t+\tNR\tNR\tTuberculosis treatment\tSurvive\t\nKim et al\t49\tM\tTuberculous lymphadenitis\t−\t+\t−\t+\tNR\tTuberculosis treatment\tSurvive\t\nIsobe et al\t54\tM\tPulmonary tuberculosis\t+\t−\t−\t+\t+\tTuberculosis treatment, Systemic corticosteroid\tSurvive\t\nCarvalho et al\t50\tM\tPulmonary tuberculosis\t−\t+\t−\t+\tNR\tNSAIDs, antihistamines\tSurvive\t\nBueno Filho et al\t45\tF\tTuberculous lymphadenitis\t+\t−\t−\t+\t+\tTuberculosis treatment\tSurvive\t\nMeziane et al\t19\tM\tPulmonary tuberculosis, Tuberculous pleurisy, Anal tuberculosis\t−\t+\t+\t+\t−\tTuberculosis treatment\tSurvive\t\nAbbreviations: F, female; LCV, leukocytoclastic vasculitis; M, male; NR, not reported.\n\na IgA deposition in the vessels of skin or kidney.\n\nJohn Wiley & Sons, LtdTable 2 Characteristics and outcomes in patients with IgA vasculitis complicated with tuberculosis (Onset after tuberculosis treatment)\n\nReference\tAge (year)\tSex\tType of tuberculosis\tAntituberculosis drugs\tInterval\na\n(days)\tRenal symptoms\tArthralgia/arthritis\tGastrointestinal symptoms\tLCV\tIgA deposit\nb\n\n\tTreatment\tOutcome\t\nMcLachlan\t34\tM\tTuberculous pericarditis, Tuberculous pleurisy, Pulmonary tuberculosis\tSM, INH\t20\t+\t+\t+\tNR\tNR\tSystemic corticosteroid, ACTH\tSurvive\t\n\t21\tM\tPulmonary tuberculosis\tSM, INH\t>400\t+\t+\t+\tNR\tNR\tWithdrawal of antituberculosis drugs, Systemic corticosteroid\tSurvive\t\nChan et al\t64\tM\tPulmonary tuberculosis, Tuberculous pleurisy\tINH, RFP, PZA, EB\t150\t+\t−\t−\t+\t+\tWithdrawal of antituberculosis drugs\tSurvive\t\n\t41\tM\tPulmonary tuberculosis\tINH, RFP, PZA, EB\t120\t+\t−\t−\t+\t+\tWithdrawal of antituberculosis drugs\tDeath\t\nMishima et al\t34\tM\tPulmonary tuberculosis, Tuberculous pleurisy\tINH, RFP, SM\t150\t−\t+\t−\tNR\tNR\tSystemic corticosteroid\tSurvive\t\nHan et al\t41\tM\tDisseminated tuberculosis\tUnknown\t15\t+\t−\t−\t+\t+\tTuberculosis treatment\tSurvive\t\nKitamura et al\t38\tM\tPulmonary tuberculosis\tINH, RFP, PZA, EB\t90\t+\t+\t+\t+\t+\tSystemic corticosteroid\tSurvive\t\nChanprapaph et al\t62\tM\tPulmonary tuberculosis\tINH, RFP, EB\t14\t−\t−\t−\t+\t+\tWithdrawal of antituberculosis drugs, Topical corticosteroid, Antihistamines\tSurvive\t\nBhatia et al\t14\tM\tDisseminated tuberculosis\tINH, RFP, PZA, EB\t42\t−\t−\t−\t+\t−\tWithdrawal of antituberculosis drugs, Systemic corticosteroid\tSurvive\t\nAVCU\t12\tF\tPulmonary tuberculosis\tINH, RFP, PZA, EB\t29\t−\t−\t−\t+\tNR\tWithdrawal of antituberculosis drugs, Systemic corticosteroid, Antihistamines\tSurvive\t\nGargouri et al\t29\tM\tPulmonary tuberculosis\tINH, RFP, PZA, EB\t3\t−\t+\t−\t+\t+\tWithdrawal of antituberculosis drugs\tSurvive\t\nShim and Jung\t72\tM\tPulmonary tuberculosis\tINH, RFP, EB\t14\t−\t−\t+\t+\t−\tWithdrawal of antituberculosis drugs, Systemic corticosteroid\tSurvive\t\nThis case\t71\tM\tTuberculous lymphadenitis\tINH, RFP, PZA, EB\t19\t+\t−\t+\t+\tNR\tSystemic corticosteroid\tDeath\t\nAbbreviations: EB, ethambutol; F, female; INH, isoniazid; LCV, leukocytoclastic vasculitis; M, male; NR, not reported; PZA, pyrazinamide; RFP, rifampicin; SM, streptomycin.\n\na Interval between the start of tuberculosis treatment and onset of symptoms of IgA vasculitis.\n\nb IgA deposition in the vessels of skin or kidney.\n\nJohn Wiley & Sons, LtdGastrointestinal symptoms of IgAV include abdominal pain, nausea, vomiting, and occult or overt intestinal bleeding.\n1\n, \n2\n, \n3\n The small intestine is the most frequently involved site in the gastrointestinal tract. The descending part of the duodenum is characteristically involved more often than the bulb. Endoscopic findings exhibit various forms such as diffuse mucosal redness, petechiae, hemorrhagic erosions, and ulcers.\n30\n Although symptomatic treatment alone often improves symptoms of IgAV, corticosteroids are useful in cases with severe abdominal symptoms. Corticosteroids should be considered early in cases with severe abdominal symptoms, because early corticosteroid therapy has been reported to reduce the need for abdominal surgery.\n31\n We delayed the use of corticosteroids for fear of worsening the course of tuberculosis, but this was not necessary because corticosteroids have also been reported to improve the prognosis of tuberculosis.\n32\n In addition, we could have used higher doses of corticosteroids because rifampicin has been reported to reduce the effectiveness of corticosteroids.\n33\n On the other hand, deaths caused by infections associated with the use of glucocorticoids have been reported in older adults with IgAV, and it is thought that their use requires careful attention.\n34\n\n\n\nIn summary, there are only a few reports of IgAV complicated with tuberculosis, and the case we have presented marks the first fatal case attributed to gastrointestinal tract lesions. If IgAV caused by antituberculosis drugs is suspected, discontinuation of tuberculosis treatment is usually considered, but in cases marked by severe abdominal pain or gastrointestinal bleeding, use of corticosteroids should be considered. There is no need to withhold the use of corticosteroids because of the coexistence of tuberculosis. On the contrary, patients taking rifampicin may usually need more steroids. Careful attention should be paid when administering steroids to elderly patients with IgAV, as deaths from infections have been reported.\n\nCONFLICT OF INTEREST\nThe authors declare that there is no conflict of interest regarding the publication of this article.\n\nAUTHOR CONTRIBUTIONS\nNY: wrote the manuscript. ST, SK, AO, MK, TA, TM, JY and AM: revised the manuscript. SF: supervised the final draft.\n\nACKNOWLEDGMENTS\nThe authors would like to thank Enago (www.enago.jp) for the English language review.\n==== Refs\nREFERENCES\n1 \n\nAudemard‐Verger \nA \n, \nPillebout \nE \n, \nGuillevin \nL \n, \nThervet \nE \n, \nTerrier \nB \n. IgA vasculitis (Henoch–Shönlein purpura) in adults: Diagnostic and therapeutic aspects\n. Autoimmun Rev . 2015 ;14 (7 ):579 ‐585\n.25688001 \n2 \n\nHetland \nL \n, \nSusrud \nK \n, \nLindahl \nK \n, \nBygum \nA \n. Henoch‐Schönlein Purpura: a literature review\n. Acta Derm‐venereol . 2017 ;97 (10 ):1160 ‐1166\n.28654132 \n3 \n\nEbert \nE \n. Gastrointestinal manifestations of Henoch‐Schonlein Purpura\n. Digest Dis Sci . 2008 ;53 (8 ):2011 ‐2019\n.18351468 \n4 \n\nRigante \nD \n, \nCastellazzi \nL \n, \nBosco \nA \n, \nEsposito \nS \n. Is there a crossroad between infections, genetics, and Henoch‐Schönlein purpura?\n\nAutoimmun Rev . 2013 ;12 (10 ):1016 ‐1021\n.23684700 \n5 \n\nJennette \nJC \n, \nFalk \nRJ \n, \nBacon \nPA \n, et al, 2012 revised international Chapel Hill consensus conference nomenclature of Vasculitides\n. Arthritis Rheum . 2013 ;65 (1 ):1 ‐11\n.23045170 \n6 \n\nMills \nJ \n, \nMichel \nB \n, \nBloch \nD \n, et al, The American College of Rheumatology 1990 criteria for the classification of Henoch‐Schönlein purpura\n. Arthritis Rheum . 1990 ;33 (8 ):1114 ‐1121\n.2202310 \n7 \n\nOzen \nS \n, \nPistorio \nA \n, \nIusan \nS \n, et al, EULAR/PRINTO/PRES criteria for Henoch‐Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria\n. Ann Rheum Dis . 2010 ; 69 (5 ): 798 ‐806\n.20413568 \n8 \n\nHočevar \nA \n, \nRotar \nZ \n, \nJurčić \nV \n, et al, IgA vasculitis in adults: the performance of the EULAR/PRINTO/PRES classification criteria in adults\n. Arthritis Res Ther . 2015 ;18 (1 ):58 .\n9 \n\nChan \nCH \n, \nChong \nYW \n, \nSun \nAJ \n, \nHoheisel \nGB \n. Cutaneous vasculitis associated with tuberculosis and its treatment\n. Tubercle . 1990 ;71 (4 ):297 ‐300\n.2267682 \n10 \n\nDalgleish \nA \n. Anaphylactoid purpura in pulmonary tuberculosis\n. BMJ . 1950 ;1 (4647 ):225 .15404996 \n11 \n\nMcLachlan \nRM \n. Tuberculosis and the Schönlein‐Henoch syndrome; report of two cases\n. Tubercle . 1958 ;39 (1 ):35 ‐37\n.13530219 \n12 \n\nWashio \nM \n, \nNanishi \nF \n, \nOnoyama \nK \n, \nFujii \nK \n, \nOhchi \nN \n, \nFujishima \nM \n. Recurrence of Henoch Schoenlein purpura nephritis associated with tuberculous pleuritis\n. Nihon Jinzo Gakkai Shi . 1988 ;30 (9 ):1087 ‐1089\n.3216550 \n13 \n\nMishima \nY \n, \nTakeuchi \nM \n, \nKamisaka \nK \n, et al, Henoch‐Schönlein purpura associated with pulmonary tuberculosis\n. (in Japanese). Kekkaku . 1994 ;69 (1 ):21 ‐25\n.8107349 \n14 \n\nHan \nBG \n, \nChoi \nSO \n, \nShin \nSJ \n, \nKim \nHY \n, \nJung \nSH \n, \nLee \nKH \n. A case of Henoch‐Schönlein purpura in disseminated tuberculosis\n. Korean J Intern Med . 1995 ;10 (1 ):54 ‐59\n.7626558 \n15 \n\nSais \nG \n, \nVidallkr \nA \n, \nJucgla \nA \n, \nPeyri \nJ \n. Tuberculous lymphadenitis presenting with cutaneous leucocytoclastic vasculitis\n. Clin Exp Dermatol . 1996 ;21 (1 ):65 ‐66\n.8689776 \n16 \n\nLee \nAY \n, \nJang \nJH \n, \nLee \nKH \n. Two cases of leukocytoclastic vasculitis with tuberculosis\n. Clin Exp Dermatol . 1998 ;23 (5 ):225 ‐226\n.10233606 \n17 \n\nMínguez \nP \n, \nBurón \nD‐P \n, \nPuche \nP \n. Pulmonary tuberculosis presenting with cutaneous leukocytoclastic vasculitis\n. Infection . 2000 ;28 (1 ):55 ‐57\n.10697796 \n18 \n\nIslek \nI \n, \nMuslu \nA \n, \nTotan \nM \n, \nGok \nF \n, \nSanic \nA \n. Henoch‐Schonlein purpura and pulmonary tuberculosis\n. Pediatr Int . 2002 ;44 (5 ):545 ‐546\n.12225561 \n19 \n\nKim \nHM \n, \nPark \nY‐BB \n, \nMaeng \nHY \n, \nLee \nS‐KK \n. Cutaneous leukocytoclastic vasculitis with cervical tuberculous lymphadenitis: a case report and literature review\n. Rheumatol Int . 2006 ;26 (12 ):1154 ‐1157\n.16830160 \n20 \n\nKitamura \nH \n, \nShimizu \nK \n, \nTakeda \nH \n, \nTai \nH \n, \nIto \nY \n, \nFukunaga \nM \n. A case of henoch‐schönlein purpura nephritis in pulmonary tuberculosis\n. Am J Med Sci . 2007 ;333 (2 ):117 ‐121\n.17301592 \n21 \n\nIsobe \nZ \n, \nSuga \nT \n, \nAoki \nY \n, et al, A case of anaphylactoid purpura associated with nephrosis followed by pulmonary tuberculosis\n. (in Japanese). Nihon Kokyuki Gakkai Zasshi . 2008 ;46 (8 ):645 ‐649\n.18788434 \n22 \n\nCarvalho \nM \n, \nDominoni \nRL \n, \nSenchechen \nD \n, \nFernandes \nAF \n, \nBurigo \nIP \n, \nDoubrawa \nE \n. Cutaneous leukocytoclastic vasculitis accompanied by pulmonary tuberculosis\n. J Bras Pneumol . 2008 ;34 (9 ):745 ‐748\n.18982211 \n23 \n\nBueno Filho \nR \n, \nCordeiro \nAP \n, \nAlmeida \nFT \n, \nShaletich \nC \n, \nCosta \nRS \n, \nRoselino \nAM \n. Rare association of cutaneous vasculitis, IgA nephropathy and antiphospholipid antibody syndrome with tuberculous lymphadenitis\n. Clinics . 2012 ;67 (12 ):1497 ‐1500\n.23295608 \n24 \n\nChanprapaph \nK \n, \nRoongpisuthipong \nW \n, \nThadanipon \nK \n. Annular leukocytoclastic vasculitis associated with anti‐tuberculosis medications: a case report\n. J Med Case Rep . 2013 ;7 :34 .23369624 \n25 \n\nBhatia \nV \n, \nSibal \nA \n, \nRajgarhia \nS \n. Antituberculosis therapy‐associated cutaneous leukocytoclastic vasculitis\n. J Trop Pediatr . 2013 ;59 (6 ):507 ‐508\n.23780994 \n26 \n\nMeziane \nM \n, \nAmraoui \nN \n, \nTaoufik \nH \n, \nMernissi \nFZ \n. Cutaneous leukocytoclastic vasculitis revealing multifocal tuberculosis\n. Int J Mycobacteriol . 2013 ;2 (4 ):230 ‐232\n.26786128 \n27 \n\nAvcu \nG \n, \nSensoy \nG \n, \nÇeliksoy \nMH \n, et al, Cutaneous leukocytoclastic vasculitis associated with anti‐tuberculosis drugs\n. Pediatr Int . 2015 ;57 (1 ):155 ‐157\n.25711253 \n28 \n\nGargouri \nI \n, \nKacem \nA \n, \nBen Salem \nH \n, et al, Adult Henoch‐Schonlein purpura and pulmonary tuberculosis\n. Tunis Med . 2017 ;95 (4 ):313 ‐314\n.29492940 \n29 \n\nShim \nS \n, \nJung \nCY \n. Cutaneous leukocytoclastic vasculitis with gastrointestinal involvement after anti‐Tuberculosis treatment\n. Tuberc Respir Dis (Seoul) . 2017 ;80 (2 ):210 ‐211\n.28416962 \n30 \n\nEsaki \nM \n, \nMatsumoto \nT \n, \nNakamura \nS \n, et al, GI involvement in Henoch‐Schönlein purpura\n. Gastrointest Endosc . 2002 ;56 (6 ):920 ‐923\n.12447314 \n31 \n\nWeiss \nPF \n, \nKlink \nAJ \n, \nLocalio \nR \n, et al, Corticosteroids may improve clinical outcomes during hospitalization for Henoch‐Schönlein purpura\n. Pediatrics . 2010 ;126 (4 ):674 ‐681\n.20855386 \n32 \n\nCritchley \nJ \n, \nYoung \nF \n, \nOrton \nL \n, \nGarner \nP \n. Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta‐analysis\n. Lancet Infect Dis . 2013 ;13 (3 ):223 ‐237\n.23369413 \n33 \n\nMcAllister \nT \n, \nAl‐Habet \nR \n. Rifampicin reduces effectiveness and bioavailability of prednisolone\n. Br Medical J Clin Res Ed . 1983 ;286 (6369 ):923 ‐925\n.\n34 \n\nUeda \nH \n, \nMiyazaki \nY \n, \nTsuboi \nN \n, et al, Clinical and pathological characteristics of elderly Japanese patients with IgA vasculitis with nephritis: a case series\n. Intern Med . 2019 ;58 (1 ):31 ‐38\n.30101942\n\n", "fulltext_license": "CC BY", "issn_linking": "2050-0904", "issue": "8(9)", "journal": "Clinical case reports", "keywords": "Henoch‐Schönlein purpura; IgA vasculitis; gastrointestinal bleeding; leukocytoclastic vasculitis; tuberculosis", "medline_ta": "Clin Case Rep", "mesh_terms": null, "nlm_unique_id": "101620385", "other_id": null, "pages": "1741-1747", "pmc": null, "pmid": "32983488", "pubdate": "2020-09", "publication_types": "D002363:Case Reports", "references": "15404996;23780994;18788434;25688001;30101942;28654132;2267682;16830160;10697796;6403136;7626558;18351468;18982211;12447314;28416962;8689776;8107349;23295608;3216550;17301592;29492940;23369413;20855386;13530219;23369624;12225561;2202310;23684700;26935833;25711253;10233606;23045170;26786128;20413568", "title": "Fatal gastrointestinal bleeding due to IgA vasculitis complicated with tuberculous lymphadenitis: A case report and literature review.", "title_normalized": "fatal gastrointestinal bleeding due to iga vasculitis complicated with tuberculous lymphadenitis a case report and literature review" }

[ { "companynumb": "JP-STRIDES ARCOLAB LIMITED-2020SP013133", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "210785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "HENOCH-SCHONLEIN PURPURA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "210785", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "450 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPH NODE TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "450", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPICIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 GRAM DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPH NODE TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "750 MILLIGRAM, THRICE A WEEK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "750", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PYRAZINAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.5 GRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPH NODE TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRAZINAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ISONIAZID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ISONIAZID." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "HENOCH-SCHONLEIN PURPURA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PYRAZINAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.5 GRAM, THRICE A WEEK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRAZINAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "210785", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ISONIAZID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "300 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPH NODE TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ISONIAZID." } ], "patientagegroup": null, "patientonsetage": "71", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug level decreased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "YAMAUCHI N, TANDA S, KASHIWAGI S, OHNISHI A, KUGAI M, AKAZAWA T, ET AL.. FATAL GASTROINTESTINAL BLEEDING DUE TO IGA VASCULITIS COMPLICATED WITH TUBERCULOUS LYMPHADENITIS: A CASE REPORT AND LITERATURE REVIEW.. CLINICAL CASE REPORTS. 2020?8(9):1741-1747", "literaturereference_normalized": "fatal gastrointestinal bleeding due to iga vasculitis complicated with tuberculous lymphadenitis a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20201030", "receivedate": "20201030", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18444294, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210114" }, { "companynumb": "JP-FRESENIUS KABI-FK202011160", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "091181", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPH NODE TUBERCULOSIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "450", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPIN (MANUFACTURER UNKNOWN)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ISONIAZID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPH NODE TUBERCULOSIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ISONIAZID." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PYRAZINAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPH NODE TUBERCULOSIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRAZINAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPH NODE TUBERCULOSIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" } ], "patientagegroup": null, "patientonsetage": "71", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypovolaemic shock", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Henoch-Schonlein purpura", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Gastrointestinal perforation", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "YAMAUCHI N, TANDA S, KASHIWAGI S, OHNISHI A, KUGAI M, AKAZAWA T, ET AL. FATAL GASTROINTESTINAL BLEEDING DUE TO IGA VASCULITIS COMPLICATED WITH TUBERCULOUS LYMPHADENITIS: A CASE REPORT AND LITERATURE REVIEW. CLINICAL CASE REPORTS. 2020 SEP?8 (9):1741-1747.", "literaturereference_normalized": "fatal gastrointestinal bleeding due to iga vasculitis complicated with tuberculous lymphadenitis a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20201026", "receivedate": "20201026", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18429917, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" } ]

{ "abstract": "BACKGROUND\nThe effect of maintenance steroid treatment (MST) in reducing the risk of relapse in patients with autoimmune pancreatitis (AIP) remains under debate. The aim of this study was to validate the effect of MST on AIP administered in accordance with the 2010 Japanese consensus guidelines.\n\n\nMETHODS\nThe clinical data of patients with (n = 510) from 22 high-volume centers in Japan were studied. The primary endpoints were the relapse rates (RRs) in patients administered MST versus those not administered MST. The secondary endpoints were the optimal dose and duration of MST in terms of steroid toxicity and the predictors of relapse.\n\n\nRESULTS\nThe RRs were 10.0% within 1 year, 25.8% within 3 years and 35.1% within 5 years. The RR in the steroid therapy group reached a plateau at 42.7% at 7 years. In terms of the optimal dosage, the overall RR in the MST 5 mg/day group was 26.1%, which was significantly lower than that in the group which had discontinued steroid therapy (45.2%; p = 0.023) or was receiving MST at 2.5 mg/day (43.4%, p = 0.001). The RRs in the group receiving MST at ≥5 mg/day versus the patient group receiving MST at <5 mg/day were 10.6 vs. 10.3% within 1 year, 23.5 vs. 32.9% within 3 years and 32.2 vs. 41.3% within 5 years, respectively (log-rank, p = 0.028). The best cutoff value of the total steroid dose for serious steroid toxicity was 6405 mg, with a moderate accuracy of 0.717 determined using the area under the curve. Presence of diffuse pancreatic swelling [odds ratio OR) 1.745; p = 0.008) and MST at >5 mg/day were identified as predictors of relapse (OR 0.483; p = 0.001).\n\n\nCONCLUSIONS\nThe RR could continue to increase for 7 years even under MST. Based on our analysis of the side effects of steroid therapy, MST at 5 mg/day for 2 (total 4625 mg) to 3 (total 6425 mg) years might be a rational and safe therapeutic strategy in terms of keeping the RR to <30% while avoiding potential steroid toxicity.", "affiliations": "Department of Endoscopy, Yokohama City University Hospital, Yokohama, Japan.;Department of Internal Medicine, Tokyo Komagome Metropolitan Hospital, Tokyo, Japan. kamisawa@cick.jp.;Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan.;Center for Health, Safety and Environmental Management, Shinshu University, Matsumoto, Japan.;Department of Gastroenterology, Graduate School of Medicine, Tokyo University, Tokyo, Japan.;Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan.;Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan.;Department of Gastroenterology, Graduate School of Medicine, Kobe University, Kobe, Japan.;Department of Community-Based Medical Education, Graduate School of Medicine, Nagoya City University, Nagoya, Japan.;Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.;Department of Gastroenterology, Graduate School of Medicine, Shinshu University, Matsumoto, Japan.;Department of Gastroenterology, Graduate School of Medicine, Tohoku University, Sendai, Japan.;Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.;Department of Gastroenterology, Tokyo Medical University, Tokyo, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medicine, Kyushu University, Fukuoka, Japan.;Department of Gastroenterology, Chikushi Hospital, Fukuoka University, Fukuoka, Japan.;Department of Gastroenterology, Yachiyo Hospital, Tokyo Women's Medical University, Tokyo, Japan.;Department of Gastroenterology, Second Teaching Hospital, Fujita Health University, Toyoake, Japan.;Department of Gastroenterology, Aichi Cancer Center, Nagoya, Japan.;Department of Gastroenterology, School of Medicine, Showa University, Tokyo, Japan.;Department of Surgery, School of Medicine, Kyorin University, Tokyo, Japan.;Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University, Tokyo, Japan.;Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan.;Department of Gastroenterology, Graduate School of Medicine, Tohoku University, Sendai, Japan.;Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka, Japan.;Gastroenterology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.", "authors": "Kubota|Kensuke|K|;Kamisawa|Terumi|T|;Okazaki|Kazuichi|K|;Kawa|Shigeyuki|S|;Hirano|Kenji|K|;Hirooka|Yoshiki|Y|;Uchida|Kazushige|K|;Shiomi|Hideyuki|H|;Ohara|Hirotaka|H|;Shimizu|Kyoko|K|;Arakura|Norikazu|N|;Kanno|Atsushi|A|;Sakagami|Junichi|J|;Itoi|Takao|T|;Ito|Tetsuhide|T|;Ueki|Toshiharu|T|;Nishino|Takayoshi|T|;Inui|Kazuo|K|;Mizuno|Nobumasa|N|;Yoshida|Hitoshi|H|;Sugiyama|Masanori|M|;Iwasaki|Eisuke|E|;Irisawa|Atshishi|A|;Shimosegawa|Toru|T|;Takeyama|Yoshifumi|Y|;Chiba|Tsutomu|T|", "chemical_list": "D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D011239:Prednisolone; D001379:Azathioprine", "country": "Japan", "delete": false, "doi": "10.1007/s00535-016-1302-1", "fulltext": null, "fulltext_license": null, "issn_linking": "0944-1174", "issue": "52(8)", "journal": "Journal of gastroenterology", "keywords": "Autoimmune pancreatitis; Maintenance steroid treatment; Relapse rate; Steroid toxicity", "medline_ta": "J Gastroenterol", "mesh_terms": "D000368:Aged; D000893:Anti-Inflammatory Agents; D001327:Autoimmune Diseases; D001379:Azathioprine; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents; D007564:Japan; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D050500:Pancreatitis, Chronic; D011239:Prednisolone; D012008:Recurrence; D012307:Risk Factors; D055502:Secondary Prevention; D013997:Time Factors", "nlm_unique_id": "9430794", "other_id": null, "pages": "955-964", "pmc": null, "pmid": "28062947", "pubdate": "2017-08", "publication_types": "D016428:Journal Article; D016448:Multicenter Study", "references": "7628283;18328441;19398440;10841167;20513004;11236777;23232048;18222442;21757447;21491208;24639058;20436071;20213336;11136882;26061806;13746542;27091321;26565969;21732837;19345283;17525092;21412117", "title": "Low-dose maintenance steroid treatment could reduce the relapse rate in patients with type 1 autoimmune pancreatitis: a long-term Japanese multicenter analysis of 510 patients.", "title_normalized": "low dose maintenance steroid treatment could reduce the relapse rate in patients with type 1 autoimmune pancreatitis a long term japanese multicenter analysis of 510 patients" }

[ { "companynumb": "JP-EDENBRIDGE PHARMACEUTICALS, LLC-JP-2020EDE000006", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE SODIUM PHOSPHATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "203559", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.5?0.7 MG/KG", "drugenddate": null, "drugenddateformat": null, "drugindication": "AUTOIMMUNE PANCREATITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE SODIUM PHOSPHATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE SODIUM PHOSPHATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "203559", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "BETWEEN 2.5-7.5 MG, QD (LOW-DOSE MAINTENANCE TREATMENT)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE SODIUM PHOSPHATE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cerebral infarction", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "KUBOTA K., KAMISAWA T., OKAZAKI K., KAWA S., HIRANO K., HIROOKA Y. ET AL.. LOW-DOSE MAINTENANCE STEROID TREATMENT COULD REDUCE THE RELAPSE RATE IN PATIENTS WITH TYPE 1 AUTOIMMUNE PANCREATITIS: A LONG-TERM JAPANESE MULTICENTER ANALYSIS OF 510 PATIENTS. J GASTROENTEROL. 2017?52:955?964", "literaturereference_normalized": "low dose maintenance steroid treatment could reduce the relapse rate in patients with type 1 autoimmune pancreatitis a long term japanese multicenter analysis of 510 patients", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20200309", "receivedate": "20200309", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17514598, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200409" } ]

{ "abstract": "Raltegravir was the first licensed integrase inhibitor. Real-life experience is informative and complements trial data. We therefore evaluated raltegravir use in adults in a large HIV treatment centre. From pharmacy and departmental HIV database records, we identified all adults taking ≥1 dose of raltegravir from first availability to the end of November 2012. Data were collected using a standardised case report form. Two hundred and fifteen individuals provided 502 patient-years (median 2.6 years/person) of raltegravir use. Of 215 individuals, 166 (77%) were male, median age 43 years; 189 (88%) were antiretroviral therapy (ART)-experienced and 26 (12%) ART-naive, with median baseline CD4 counts of 324 and 54 cells/µL, respectively. Of ten individuals using once-daily raltegravir, four, with good adherence remained virologically suppressed after a median 28 months, four stopped against medical advice, one stopped to simplify and one failed virologically. In hepatitis co-infection, 35 individuals (92 patient-years) took raltegravir without evidence of hepatotoxicity. Six women started raltegravir during pregnancy for intensification (5/6) or switch for tolerability without complications. Of ten individuals stopping raltegravir after virological failure, 2/4 with successful sequencing showed resistance. Raltegravir appears safe and effective, without evidence of toxicity above that in published trials, including in pregnancy and co-infections. Once-daily dosing seems effective where adherence is good.", "affiliations": "Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Manchester, UK claretaylor@doctors.org.uk clare.vanhalsema@nhs.net.;Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Manchester, UK.;University of Manchester School of Medicine, Oxford Road, Manchester, UK.;Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Manchester, UK.;Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Manchester, UK.;Monsall Unit, Department of Infectious Diseases and Tropical Medicine, North Manchester General Hospital, Manchester, UK.", "authors": "van Halsema|Clare|C|;Whitfield|Thomas|T|;Lin|Naomi|N|;Ashton|Kathryn|K|;Torkington|Adele|A|;Ustianowski|Andrew|A|", "chemical_list": "D019428:HIV Integrase Inhibitors; D000068898:Raltegravir Potassium", "country": "England", "delete": false, "doi": "10.1177/0956462415584485", "fulltext": null, "fulltext_license": null, "issn_linking": "0956-4624", "issue": "27(5)", "journal": "International journal of STD & AIDS", "keywords": "AIDS; HAART (Highly Active Antiretroviral Therapy); HIV (Human immunodeficiency virus); antiviral; integrase inhibitor; raltegravir; toxicity; treatment; viral disease", "medline_ta": "Int J STD AIDS", "mesh_terms": "D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D060085:Coinfection; D005260:Female; D015658:HIV Infections; D019428:HIV Integrase Inhibitors; D015497:HIV-1; D006525:Hepatitis, Viral, Human; D006801:Humans; D008016:Life Change Events; D008297:Male; D011247:Pregnancy; D000068898:Raltegravir Potassium; D012189:Retrospective Studies; D016896:Treatment Outcome; D019562:Viral Load", "nlm_unique_id": "9007917", "other_id": null, "pages": "387-93", "pmc": null, "pmid": "25931236", "pubdate": "2016-04", "publication_types": "D016428:Journal Article; D064888:Observational Study", "references": null, "title": "Five years' real-life experience with raltegravir in a large HIV centre.", "title_normalized": "five years real life experience with raltegravir in a large hiv centre" }

[ { "companynumb": "GB-JNJFOC-20160327269", "fulfillexpeditecriteria": "1", "occurcountry": "GB", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "DARUNAVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "021976", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLETS", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DARUNAVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "RITONAVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITONAVIR." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "RALTEGRAVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNSPECIFIED", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RALTEGRAVIR." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Transaminases increased", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Angioedema", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Rash", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Epstein-Barr viraemia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "VAN HALSEMA C, WHITFIELD T, LIN N, ASHTON K, TORKINGTON A, USTIANOWSKI A. FIVE YEARS^ REAL-LIFE EXPERIENCE WITH RALTEGRAVIR IN A LARGE HIV CENTRE. INTERNATIONAL JOURNAL OF STD AND AIDS 01-APR-2016;27 (5):387-393.", "literaturereference_normalized": "five years real life experience with raltegravir in a large hiv centre", "qualification": "3", "reportercountry": "GB" }, "primarysourcecountry": "GB", "receiptdate": "20160408", "receivedate": "20160408", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12249808, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160815" } ]

{ "abstract": "A 14-year-old boy with 22q11.2 deletion syndrome and a right ventricular to pulmonary artery xenograft conduit presented to an Australian tertiary children's hospital with prolonged fevers, weight loss, splenomegaly and a high proportion of gamma-delta T cells in peripheral blood and bone marrow, concerning for possible gamma-delta T-cell lymphoma. However, investigations did not reveal evidence of lymphoma or autoimmune disease. After 5 months of intermittent fever episodes and ongoing symptoms, he was found to have an extremely high Bartonella henselae titre (8192) on serological testing, with the organism also detected on blood PCR. After 6 months of oral azithromycin and rifampicin, with complete resolution of his symptoms 3 months into treatment, his blood PCR was negative and gamma-delta T cells in peripheral blood were decreasing. The B. henselae titre remained unchanged for some time, but decreased to 2048 around 1 year after treatment was started.", "affiliations": "Department of Paediatrics, Monash Children's Hospital, Clayton, Victoria, Australia drkimberlyjdavis@gmail.com.;Department of Paediatrics, Monash Children's Hospital, Clayton, Victoria, Australia.;Department of Anatomical Pathology, Monash Medical Centre, Clayton, Victoria, Australia.;Department of Immunology, Monash Medical Centre, Clayton, Victoria, Australia.", "authors": "Davis|Kimberly|K|http://orcid.org/0000-0002-7169-7816;Battaglia|Lauren|L|;Kumar|Beena|B|;Ojaimi|Samar|S|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1136/bcr-2021-245592", "fulltext": null, "fulltext_license": null, "issn_linking": "1757-790X", "issue": "14(11)", "journal": "BMJ case reports", "keywords": "congenital disorders; immunology; infections", "medline_ta": "BMJ Case Rep", "mesh_terms": null, "nlm_unique_id": "101526291", "other_id": null, "pages": null, "pmc": null, "pmid": "34848411", "pubdate": "2021-11-30", "publication_types": "D016428:Journal Article", "references": null, "title": "Bartonella henselae masquerading as possible gamma-delta T-cell lymphoma in a paediatric patient with 22q11.2 deletion syndrome.", "title_normalized": "bartonella henselae masquerading as possible gamma delta t cell lymphoma in a paediatric patient with 22q11 2 deletion syndrome" }

[ { "companynumb": "AU-MYLANLABS-2022M1029869", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "CEFTAZIDIME" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Cat scratch disease", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTAZIDIME" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "AZITHROMYCIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "065360", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Cat scratch disease", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZITHROMYCIN" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "AZITHROMYCIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "065360", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": "6", "drugtreatmentdurationunit": "802", "medicinalproduct": "AZITHROMYCIN" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "065421", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Cat scratch disease", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPIN" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "065421", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": "6", "drugtreatmentdurationunit": "802", "medicinalproduct": "RIFAMPIN" } ], "patientagegroup": null, "patientonsetage": "14", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Davis K, Battaglia L, Kumar B, Ojaimi S. Bartonella henselae masquerading as possible gamma-delta T-cell lymphoma in a paediatric patient with 22q11.2 deletion syndrome. BMJ-Case-Rep 2021;14:No. 11.", "literaturereference_normalized": "bartonella henselae masquerading as possible gamma delta t cell lymphoma in a paediatric patient with 22q11 2 deletion syndrome", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220425", "receivedate": "20220425", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20744806, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220721" }, { "companynumb": "AU-LUPIN PHARMACEUTICALS INC.-2022-06208", "fulfillexpeditecriteria": "2", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZITHROMYCIN" }, "drugadditional": "4", "drugadministrationroute": "048", "drugauthorizationnumb": "065398", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Cat scratch disease", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZITHROMYCIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZITHROMYCIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "065398", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": "6", "drugtreatmentdurationunit": "802", "medicinalproduct": "AZITHROMYCIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "090034", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Cat scratch disease", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "090034", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": "6", "drugtreatmentdurationunit": "802", "medicinalproduct": "RIFAMPIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CEFTAZIDIME" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Cat scratch disease", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTAZIDIME" } ], "patientagegroup": null, "patientonsetage": "14", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective for unapproved indication", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Davis K, Battaglia L, Kumar B, Ojaimi S. Bartonella henselae masquerading as possible gamma-delta T-cell lymphoma in a paediatric patient with 22q11.2 deletion syndrome. BMJ Case Reports. 2021;14(11):e245592:1-5", "literaturereference_normalized": "bartonella henselae masquerading as possible gamma delta t cell lymphoma in a paediatric patient with 22q11 2 deletion syndrome", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220428", "receivedate": "20220428", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20761522, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" } ]

{ "abstract": "Alemtuzumab is effective in relapsing remitting multiple sclerosis (RRMS). Serious adverse events have led to a renewed safety reassessment by the European Medicines Agency (EMA), leading to an approval under strict conditions. We report a RRMS patient experiencing diffuse alveolar hemorrhage (DAH) on day 4 of her first alemtuzumab cycle. In addition, we present an overview of the cases of alemtuzumab-induced DAH that were included in EMA's review procedure, additional well documented cases reported to the EMA and those cases reported in the literature. Combining these cases revealed striking similarities. Importantly, DAH was an early complication. All RRMS patients with known outcome showed complete recovery.", "affiliations": "Department of Neurology, Albert Schweitzer hospital, post office box 444, 3300AK, Dordrecht, Netherlands.;Department of Neurology, Albert Schweitzer hospital, post office box 444, 3300AK, Dordrecht, Netherlands.;Department of Neurology, Erasmus Medical Center, post office box 2040, 3000CA, Rotterdam, Netherlands.;Department of Neurology, Amsterdam UMC, location VUmc, post office box 7057, 1007 MB, Amsterdam, Netherlands.;Department of Pulmonology, Albert Schweitzer hospital, post office box 444, 3300AK, Dordrecht, Netherlands.;Department of Radiology, Albert Schweitzer hospital, post office box 444, 3300AK, Dordrecht, Netherlands.;Department of Hematology, Albert Schweitzer hospital, post office box 444, 3300AK, Dordrecht, Netherlands.;Department of Neurology, Albert Schweitzer hospital, post office box 444, 3300AK, Dordrecht, Netherlands. Electronic address: beukelaarj@asz.nl.", "authors": "Drop|B R H|BRH|;Zemel|D|D|;Wokke|B H A|BHA|;van Oosten|B W|BW|;Dik|S|S|;Martins Jarnalo|C O|CO|;Westerweel|P E|PE|;de Beukelaar|J W K|JWK|", "chemical_list": "D000074323:Alemtuzumab", "country": "Netherlands", "delete": false, "doi": "10.1016/j.msard.2020.102614", "fulltext": null, "fulltext_license": null, "issn_linking": "2211-0348", "issue": "47()", "journal": "Multiple sclerosis and related disorders", "keywords": "Adverse events; Alemtuzumab; Diffuse alveolar hemorrhage; Hemoptysis; Multiple sclerosis; Respiratory symptoms", "medline_ta": "Mult Scler Relat Disord", "mesh_terms": "D000074323:Alemtuzumab; D005260:Female; D006470:Hemorrhage; D006801:Humans; D008171:Lung Diseases; D009103:Multiple Sclerosis; D020529:Multiple Sclerosis, Relapsing-Remitting", "nlm_unique_id": "101580247", "other_id": null, "pages": "102614", "pmc": null, "pmid": "33249378", "pubdate": "2021-01", "publication_types": "D002363:Case Reports; D016422:Letter", "references": null, "title": "Diffuse alveolar hemorrhage as an early complication of alemtuzumab treatment: A case report of a multiple sclerosis patient and an overview of 14 cases.", "title_normalized": "diffuse alveolar hemorrhage as an early complication of alemtuzumab treatment a case report of a multiple sclerosis patient and an overview of 14 cases" }

[ { "companynumb": "NL-SA-2018SA281745", "fulfillexpeditecriteria": "1", "occurcountry": "NL", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "ALEMTUZUMAB" }, "drugadditional": "1", "drugadministrationroute": "041", "drugauthorizationnumb": "103948", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": "60", "drugcumulativedosageunit": "003", "drugdosageform": "CONCENTRATE FOR SOLUTION FOR INFUSION", "drugdosagetext": "12 MG, QD", "drugenddate": "20181004", "drugenddateformat": "102", "drugindication": "RELAPSING-REMITTING MULTIPLE SCLEROSIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "20181001", "drugstartdateformat": "102", "drugstructuredosagenumb": "12", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEMTRADA" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CLEMASTINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "2 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "PREMEDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2018", "drugstartdateformat": "602", "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLEMASTINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ACETAMINOPHEN" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "1000 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "PREMEDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2018", "drugstartdateformat": "602", "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PARACETAMOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NITROFURANTOIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "LONG TIME MAINTENANCE 1X50 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NITROFURANTOINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PANTOPRAZOLE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "40 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "2018", "drugstartdateformat": "602", "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PANTOPRAZOL [PANTOPRAZOLE]" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VALACYCLOVIR HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "12", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "2018", "drugstartdateformat": "602", "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VALACYCLOVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "960 MG, TIW", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": "2018", "drugstartdateformat": "602", "drugstructuredosagenumb": "960", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "COTRIMOXAZOLE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ACYCLOVIR" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, Q12H", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "12", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACICLOVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "PREMEDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2018", "drugstartdateformat": "602", "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLON [METHYLPREDNISOLONE]" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pulmonary alveolar haemorrhage", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Haemoptysis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Chest discomfort", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cough", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Dyspnoea", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypoxia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20181004" } }, "primarysource": { "literaturereference": "DROP BRH, ZEMEL D, WOKKE BHA, VAN OOSTEN BW, DIK S, MARTINS JARNALO CO, ET AL.. DIFFUSE ALVEOLAR HEMORRHAGE AS AN EARLY COMPLICATION OF ALEMTUZUMAB TREATMENT: A CASE REPORT OF A MULTIPLE SCLEROSIS PATIENT AND AN OVERVIEW OF 14 CASES. MULT SCLER RELAT DISORD.. 2021?47:UNKNOWN", "literaturereference_normalized": "diffuse alveolar hemorrhage as an early complication of alemtuzumab treatment a case report of a multiple sclerosis patient and an overview of 14 cases", "qualification": "1", "reportercountry": "NL" }, "primarysourcecountry": "NL", "receiptdate": "20210105", "receivedate": "20181023", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15541282, "safetyreportversion": 5, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210419" } ]

{ "abstract": "BACKGROUND\nHepatocellular carcinoma (HCC) metastases to the zygomatic bone are extremely uncommon, and the treatment of target drugs against such case is unknown.\nA 48-year-old male patient was admitted to our hospital under suspicion of an advanced liver tumor due to an increase in levels of alpha-fetoprotein (AFP) after radiofrequency ablation for independent nodule in his liver 1 month before. He had a hepatitis B virus (HBV) history for 20 years without treatment.\nA diagnosis of primary HCC was made based on pathological examination following right hepatectomy. Seven months after the surgery, a mass in S8 was identified and treated by ARF. Twenty days later, a right zygomatic mass was observed and the incisional biopsy revealed metastasis from HCC. Due to side effects of chemotherapy, the metastatic zygomatic mass was treated with radioactive seed implantation. Despite these interventions, there was steady increase in AFP values as well as increase in size of the zygomatic mass. Hence, the patient was started on apatinib with a dose of 500 mg/day from 1 to 28 days per cycle for a duration of 10 months.\n\n\nRESULTS\nThe AFP values were significantly decreased but the size of the zygomatic mass continued to increase indicating progression of disease. But the progression-free survival was more than 10 months. The patient exhibited adverse reactions which were controllable by symptomatic treatments. As of last follow-up, the patient is unwell with pain in the face, blurred vision in the right eye, dyscrasia, and exhibited difficulty in opening his mouth.\n\n\nCONCLUSIONS\nHCC metastases to the zygomatic bone are very aggressive with a very low incidence and immunohistochemistry is useful diagnostic indicators. Still now, there is no optimal treatment strategy for these patients. Apatinib may be a promising drug in the treatment of HCC metastases to the zygomatic bone.", "affiliations": "Department of Hepatopancreatic Surgery.;Department of Hepatopancreatic Surgery.;Department of Clinical Laboratory, The First People's Hospital of Foshan, the Affiliated Foshan Hospital of Sun Yat-Sen University, Guangdong Province, China.;Department of Hepatopancreatic Surgery.;Department of Hepatopancreatic Surgery.;Department of Hepatopancreatic Surgery.;Department of Hepatopancreatic Surgery.;Department of Hepatopancreatic Surgery.;Department of Hepatopancreatic Surgery.", "authors": "Lei|Qiucheng|Q|;Chen|Huanwei|H|;Zheng|Huazhen|H|;Deng|Feiwen|F|;Wang|Fengjie|F|;Li|Jieyuan|J|;Hu|Jianyuan|J|;Fu|Rongdang|R|;Zhen|Zuojun|Z|", "chemical_list": "D047428:Protein Kinase Inhibitors; D011725:Pyridines; D000509:alpha-Fetoproteins; C553458:apatinib", "country": "United States", "delete": false, "doi": "10.1097/MD.0000000000014595", "fulltext": "\n==== Front\nMedicine (Baltimore)Medicine (Baltimore)MEDIMedicine0025-79741536-5964Wolters Kluwer Health 31045756MD-D-18-0567710.1097/MD.0000000000014595145954500Research ArticleClinical Case ReportZygomatic bone metastasis from hepatocellular carcinoma and the therapeutic efficacy of apatinib A case report and literature reviewLei Qiucheng MDaChen Huanwei MDa∗Zheng Huazhen MDbDeng Feiwen MDaWang Fengjie MDaLi Jieyuan MDaHu Jianyuan MDaFu Rongdang MDaZhen Zuojun MDaNA. a Department of Hepatopancreatic Surgeryb Department of Clinical Laboratory, The First People's Hospital of Foshan, the Affiliated Foshan Hospital of Sun Yat-Sen University, Guangdong Province, China.∗ Correspondence: Huanwei Chen, No. 81 Lingnan North Road, Chancheng District, Foshan, Guangdong Province, China (e-mail: chwei_fsyyy@163.com).5 2019 03 5 2019 98 18 e145958 9 2018 19 1 2019 28 1 2019 Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.2019This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0Abstract\nRationale:\nHepatocellular carcinoma (HCC) metastases to the zygomatic bone are extremely uncommon, and the treatment of target drugs against such case is unknown.\n\nPatient concerns:\nA 48-year-old male patient was admitted to our hospital under suspicion of an advanced liver tumor due to an increase in levels of alpha-fetoprotein (AFP) after radiofrequency ablation for independent nodule in his liver 1 month before. He had a hepatitis B virus (HBV) history for 20 years without treatment.\n\nDiagnosis and interventions:\nA diagnosis of primary HCC was made based on pathological examination following right hepatectomy. Seven months after the surgery, a mass in S8 was identified and treated by ARF. Twenty days later, a right zygomatic mass was observed and the incisional biopsy revealed metastasis from HCC. Due to side effects of chemotherapy, the metastatic zygomatic mass was treated with radioactive seed implantation. Despite these interventions, there was steady increase in AFP values as well as increase in size of the zygomatic mass. Hence, the patient was started on apatinib with a dose of 500 mg/day from 1 to 28 days per cycle for a duration of 10 months.\n\nOutcomes:\nThe AFP values were significantly decreased but the size of the zygomatic mass continued to increase indicating progression of disease. But the progression-free survival was more than 10 months. The patient exhibited adverse reactions which were controllable by symptomatic treatments. As of last follow-up, the patient is unwell with pain in the face, blurred vision in the right eye, dyscrasia, and exhibited difficulty in opening his mouth.\n\nLessons:\nHCC metastases to the zygomatic bone are very aggressive with a very low incidence and immunohistochemistry is useful diagnostic indicators. Still now, there is no optimal treatment strategy for these patients. Apatinib may be a promising drug in the treatment of HCC metastases to the zygomatic bone.\n\nKeywords\ncancerhepatocellular carcinomametastasiszygomatic boneOPEN-ACCESSTRUE\n==== Body\n1 Introduction\nLiver cancer is one of the commonest cancers and specifically hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer death worldwide.[1,2] Approximately, 85% of HCCs occur in developing countries, and 54% occur in China.[3] A literature review showed that HCC ranks fifth in the number of new cases each year and second in cancer-related deaths annually among men.[4] HCC usually metastasizes through blood or lymphatic dissemination; metastasis to the lungs (55%) is the most common, followed by the abdominal lymph nodes (41%) or bones (28%).[5] According to the English-language literature, metastases from HCC to osseous structures in the head are extremely rare, particularly to the zygomatic bone.[6] Here, we report a case of HCC metastasizing to the zygomatic bone. To the best of our knowledge, only 3 other cases similar to ours have been previously reported.\n\nApatinib, a new and highly selective small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, was approved for advanced gastric cancer in China in Oct 2014.[7] It is reported to markedly improve the overall survival of patients with metastatic gastric adenocarcinoma.[8] Some clinical studies showed that multiline treatment combined with apatinib may prolong the survival of patients with advanced HCC.[9,10] A phase II randomized, open-label trial also indicated that apatinib is well tolerated and effective for the treatment of advanced HCC and has potential survival benefit.[11] So far, there is no report to evaluate its efficacy and safety in patient with advanced HCC with a zygomatic bone metastasis. Here, we reported 1 case using apatinib on treatment of advanced HCC with bone metastasis.\n\n2 Case report\nOn April 6, 2016, a 48-year-old Chinese patient was admitted to our hospital under suspicion of an advanced liver tumor due to an increase in levels of alpha-fetoprotein (AFP) after radiofrequency ablation. Before being referred to our hospital, an independent nodule in his left lobe and liver cancer were diagnosed via computed tomography (CT) and were treated using radiofrequency ablation (ARF) 1 month before at a local hospital. Family, alcohol consumption, and smoking histories were otherwise unremarkable, except for the history of clonorchis sinensis, with his last rhinological examination being conducted 3 months before. He presented with hepatitis B virus (HBV) history for 20 years without treatment. Examination showed no abdominal distension or pain. Initial investigations revealed raised levels of AFP (2004 ug/L) and HBV DNA (<500 IU/mL), and the laboratory tests did not reveal any liver dysfunction. Ultrasonography indicated hepatocirrhosis, with a right posterior liver lobe mass (S6) 3 cm in diameter. On the magnetic resonance (MR) scan, some areas of necrosis in the left lobe (post-treatment change), 2 independent nodules in the right posterior liver, and several swollen lymph nodes in the hepatic portal and retroperitoneum were observed (Fig. 1). Whole-body positron emission tomography/CT (PET/CT) showed a heterogeneous, encapsulated, hypodense right lobe mass with one area of high fluorine-18 fluorodeoxyglucose (FDG) metabolism (Fig. 2). The lesion was hyper-vascular and was supplied mainly by the right hepatic artery, suggesting a diagnosis of intrahepatic metastasis from the left HCC.\n\nFigure 1 Abdominal magnetic resonance (MR) scan showing 2 independent masses in the right posterior liver.\n\nFigure 2 Positron emission tomography/CT (PET/CT) demonstrating 2 hepatic mass. PET/CT = positron emission tomography/ computed tomography.\n\nOn April 12, 2016, a right hepatectomy enlarged to segment VI was performed. Histological examination of the lesion suggested primary HCC (Fig. 3A). The tumor cells were immunohistochemically positive for hepatocytes, AFP, and hepatitis B surface antigen (HBsAg). The patient successfully recovered after surgery and all biochemical marker levels returned to normal. Chemotherapy was no given after the hepatectomy. Seven months after the surgery, an ultrasonography was performed, which showed a liver lobe mass 2 cm in diameter in the right lobe (S8). Upon admission to our hospital, his laboratory test results were normal except for raised AFP levels of 281.3 ug/L (normal range, 0–20 ug/L). Abdominal imaging methods (contrast-enhanced ultrasound and MR imaging) successfully revealed metastatic disease in the liver. Because of the small size of the tumor, the patient was planned for an ARF treatment.\n\nFigure 3 A: Photomicrographs showing a large mass of tumor cells in the liver tissue (Hematoxylin-eosin × 10); B: Biopsy findings of the right zygomatic bone metastasis showing a large of polygonal tumor cells (Hematoxylin-eosin × 10); C: Hepatocyte immunohistochemical stain showing strong and diffuse positivity in the cytoplasm of tumor cells (Streptavidin-biotin × 10).\n\nTwenty days later, he developed a tender, light zygomatic mass. At that time, physical examination revealed a 4×3-cm2 bony mass in the right zygomaxillary region. The skin of the right zygomatic was slightly inflamed, but not ulcerative. The mucosa overlying the oral cavity was normal. A CT scan of the jaw demonstrated a mixed-density mass in the zygomatic arch (Fig. 4A). The mass included bony material and a cyst-like area, along with destruction of the bone. Whole-body bone scanning detected a solid and soft-tissue mass, along with increased metabolism in the right zygomatic arch. Laboratory analysis showed elevated AFP levels (4315 ug/L). An incisional biopsy was conducted, and histopathologic examination revealed a neoplasm that was composed of large heteromorphic cells (Fig. 3B). Immunohistochemical analysis showed strong and diffuse cytoplasmic positivity with hepatocytes (human hepatocyte-specific antibody) (Fig. 3C). The tumor was also positive for cytokeratin (CK) and CK19 staining. The Ki-67 proliferative index was 40% in the tumor cells. Based on the pathology results of tumor biopsy, the zygomatic mass was diagnosed as metastasis from HCC. The patient had been treated only with 2 cycles of chemotherapy (gemcitabine 1.6 g intravenous (IV) drip + oxaliplatin 135 mg IV drip + calcium levofolinate 300 mg IV drip + 5-Fluorouracil 4.35 g IV drip) in the cancer center of our hospital; subsequently, he suffered severe myelosuppression and the relevant therapy was administered. He then underwent 2 courses of oral and maxillofacial radioactive seed implantation at Sun Yat-sen University Cancer Center (Guangzhou, China).\n\nFigure 4 A: Facial computed tomography (CT) scan revealing a mixed-density mass in the right zygomatic arch; B: CT scan showing enlarged metastatic lesions in the right zygomatic arch.\n\nIn September 2016, he presented to the clinic with a complaint of a painful, soft mass in the right zygomatic region that had been slowly enlarging during the previous 16 months. Examination showed an 8 × 5-cm2 mass in the right face and laboratory tests revealed raised AFP levels (38,475.0 ug/L, normal range: 0–20). During treatment, the AFP marker levels continuously increased (Fig. 5). Due to chemotherapy intolerance, he started taking orally apatinib with a dose of 500 mg/day from 1 to 28 days per cycle. He accepted the treatment for 10 months from August 2017. At the last follow-up in June 2018, the AFP marker levels decreased to 3992 ug/L, but the follow-up CT scan showed that zygomatic target lesions were much bigger. (Fig. 4B). The patient suffered a slight impairment of liver function and mildly elevated blood pressure, but these adverse effects were controllable. He was unwell with a pain in the face, blurred vision in the right eye, dyscrasia, and exhibited difficulty in opening his mouth. He was treated only with symptomatic therapy. This report was approved by the institutional review board of the First People's Hospital of Foshan, and the patient provided written informed consent.\n\nFigure 5 The changes of AFP levels for this patient during the follow-up. AFP = alpha-fetoprotein.\n\n3 Discussion\nHCC is a prominent malignancy that is clinically silent for most of its course, and most patients are diagnosed at an advanced stage of the disease. Despite considerable knowledge about its nature and pathological process, this malignancy remains incurable. The general prognosis of HCC is poor with 5-year survival rate of less than 20%.[12] Most patients succumb to HCC within a year of diagnosis, and the survival is only 5 months if left untreated.[13,14] Metastases from HCC have extremely poor prognoses. Extrahepatic spread is also common with the most common sites of metastasis being the lungs, intra-abdominal lymph nodes, bones, and adrenal glands.[4] Bone metastases from HCC are uncommon, with a reported incidence ranging from 3 to 20%.[15,16] However, metastases to the bones of the head and neck region are extremely rare. In a study by Chin et al, 48 cases of metastatic HCC presented in the head and neck region, and most of them were usually observed in the oral cavity, maxilla, or mandible. [17]\n\nUntil recently, zygomatic bone involvement from HCC was very rarely described. Only 3 cases have been reported thus far (Table 1).[6,18,19] All patients with metastases of HCC in the zygomatic region were men, with a mean age of 60 years (range: 52–70 years).[6,18,19] Our patient was a 48-year-old man, who was younger than the patients of other published cases. The histology of the primary liver tumor was HCC in 2 of the reported cases and the other case was not reported. Two cases reported that the HCC metastasized to the left zygomatic bones; metastasis of the other case was to the right zygomatic arch, which is similar to that in our case. Dimensions of primary liver tumors have been declared only in one of the published papers (114 mm), which is much larger than the primary liver tumor in our patient (4 mm). In the previous cases, the dimensions of zygomatic metastases range from 30 mm to 60 mm. The metastasis in our case was larger, that is, 80 mm in diameter (anaphase), which was because of the 18-month duration of metastatic growth after the diagnosis.\n\nTable 1 Summary of the cases reporting of zygomatic bone metastasis from hepatocellular carcinoma.\n\nClinically, HCC is diagnosed when the tumor shows diffuse cell proliferation without the typical histological patterns of liver cells using routine hematoxylin - eosin staining (HE). Immunohistochemistry might be very useful for the diagnosis of maxillary metastasis from HCC.[20,21] Hepatocyte antigens are widely distributed in the hepatic cells and are considered the most useful markers to confirm HCC. In the present case, the tumor was positive for hepatocyte antigens upon incisional biopsy of the right zygomatic mass, and an enhanced Ki-67 proliferative index was observed. Therefore, the tumor was diagnosed as a zygomatic bone metastasis from HCC. For the diagnosis of zygomatic bone metastasis from HCC, HCC as an initial presentation is also vital. The patient in our study was already aware of the presence of the primary liver tumor, similar to the case reported in a study by Neff et al[19] Hence, in the studies by Reichbach et al[18] and Tomanovic et al[6], the zygomatic metastasis from HCC was an initial presentation of a malignant liver tumor.\n\nNone of the 3 previous cases harbored any background liver disease, such as cirrhosis or hepatitis.[6,18,19] One reported case exhibited a 30-year history of consuming large amounts of alcohol daily.[18] In the present case, our patient suffered hepatitis B liver cirrhosis for 20 years. No cases have been reported with changes in AFP levels. Our patient's preoperative (liver resection) AFP levels were elevated. Postoperatively, the AFP levels decreased, but did not return to normal. After finding the zygomatic malignant lesion, the AFP levels continuously increased, indicating an unfavorable prognosis. There have been 2 reports describing the imaging characteristics of zygomatic bone metastases from HCC.[6,19] According to these cases, zygomatic bone metastases from HCC corresponded to a soft-tissue-density characteristic observed on CT and bone scans. There was no report of MR images of this type of tumor. In the present case, as in other malignant tumors, the tumor was observed as a low-intensity mass on T1-weighted MR images and as a high-intensity area on T2-weighted MR images. All imaging findings suggested that the present tumor was a hypovascular mass.\n\nBone metastases from HCC, in particular, result in extremely poor patient prognosis, with a median survival of only 1 to 2 months.[22] Because of the rarity of zygomatic bone metastases from HCC, optimal treatment strategies are not well-defined. The prognosis of patients with zygomatic bone metastases from HCC is unfavorable, even when complete resection of the tumor is performed. Two studies reported surgical resection for metastasis, with 3 and 12 survival months after the diagnosis, respectively.[18,19] In our case, surgery was not recommended because of widespread metastases in the liver and high surgical risk. Our patient was treated with chemotherapy and radioactive seed implantation in consideration of the patient's age and performance status; however, the therapy was ineffective. Huang et al reported a case of sinonasal metastases from HCC, with a survival of only 5 months.[23] There is no solid evidence for the efficacy of those treatments in patients with bone metastases from advanced HCC. Treatment for bone metastases from HCC might be aimed at palliation of symptoms. Radiation therapy has previously been shown to provide effective palliation for skeletal metastases in patients with HCC. A study by Seong et al revealed that the median survival from the occurrence of bone metastasis from HCC was 5 months, with a 1-year survival of 15%.[24] Another study conducted by Choi et al reported the effectiveness of palliation for spinal metastases from HCC.[25] In our case, radiation therapy was not recommended because of high hemorrhage risk.\n\nA lot of target drugs against advanced HCC are constantly emerging from clinical trials. So far, sorafenib is still the standard treatment for advanced HCC, and it has been proved to be effective in prolonging overall survival in those patients.[26] However, the response rates of HCC to sorafenib were relative low, and the extended survival was also limited.[9] In recent years, apatinib, a small-molecule orally antiangiogenic agents that highly selectively and strongly inhibits vascular endothelial growth factor receptor 2, came to light due to its positive clinical efficacy on some advanced solid tumors, such as gastric cancer,[8] non-small cell lung cancer[27] and HCC.[9] Apatinib shows antitumor efficacy in several established human tumor xenograft models when administered alone or in combination with chemotherapeutic drugs.[28] According to the English literature, there are 5 reports on the therapeutic efficacy of apatinib alone or combined with radiotherapy/transcatheter hepatic arterial chemoembolization (TACE) to advanced liver cancer thus far.[29–32,10] All of them nearly exhibited that exhibited exciting effects and good safety profile. Zhu et al[32] reported that apatinib was efficient for HCC patient with big paraspinal metastasis and they think that it may function as a radiosensitizer of HCC. In our case, the patient took apatinib for maintenance therapy, and AFP marker levels were decreased, the zygomatic tumor mass have become bigger and he was confirmed as progressive disease by the Response Evaluation Criteria in Solid Tumors, however, the progression-free survival time is more than 10 months. It seems that apatinib extended his progression-free survival time and may be pays a potential antitumor role on the course of this patient's treatment to some extent. However, more research is needed to prove the clinical benefits of apatinib.\n\nIn summary, HCC metastases to the zygomatic bone are very aggressive with a very low incidence; this case is, to our knowledge, the fourth recorded case of zygomatic bone metastasis from HCC. Immunohistochemistry results with hepatocytes, combined with raised AFP levels and primary liver cancer, are useful diagnosis indicators. Because of their rarity, there is no optimal treatment strategy for these patients and their outcome is poor. In a word, zygomatic bone metastases from HCC represent a challenging clinical problem, and further large-scale prospective studies are needed to prove the therapeutic efficacy of apatinib.\n\nAcknowledgments\nAuthors would like to thank Mrs. Wenting Chen and Mrs. Jiemin Ling from LinkDoc Inc for assistance and data collection from LinkDoc Data.\n\nAuthor contributions\nData curation: Qiucheng Lei, Huazhen Zheng, Jianyuan Hu, Rongdang Fu.\n\nMethodology: Fengjie Wang, Jieyuan Li.\n\nProject administration: Feiwen Deng.\n\nWriting – original draft: Qiucheng Lei, Huazhen Zheng.\n\nWriting – review & editing: Huanwei Chen, Zuojun Zhen.\n\nAbbreviations: AFP = alpha-fetoprotein, ARF = radiofrequency ablation, CK = cytokeratin, CT = computed tomography, FDG = fluorodeoxyglucose, HBsAg = hepatitis B surface antigen, HBV = hepatitis B virus, HCC = Hepatocellular carcinoma, HE = hematoxylin-eosin staining, IV = intravenous, MR = magnetic resonance, PET/CT = positron emission tomography/ computed tomography, TACE = transcatheter hepatic arterial chemoembolization.\n\nWritten informed consent was obtained from the patient for publications of this manuscript and accompanying images.\n\nThis study was supported, in part, by the Basic Research Platform of Universities and Hospitals in Foshan, Guangdong (Project No. 2016AG100561).\n\nThe authors have no conflicts of interest to disclose.\n==== Refs\nReferences\n[1] Ferenci P Fried M Labrecque D \nHepatocellular carcinoma (HCC): a global perspective . J Clin Gastroenterol \n2010 ;44 :239–45 .20216082 \n[2] Tang A Hallouch O Chernyak V \nEpidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis . Abdom Radiol \n2017 ;43 :1–3 .\n[3] Ferlay J Shin HR Ervik M \nGLOBOCAN 2008 v1.2, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 10 [Internet] . Lyon, France : International Agency for Research on Cancer ; 2010 \nhttp://globocan.iarc.fr \n(accessed December 4, 2011).\n[4] Torre LA Bray F Siegel RL \nGlobal cancer statistics, 2012 . CA Cancer J Clin \n2015 ;65 :87–108 .25651787 \n[5] Pawarode A Voravud N Sriuranpong V \nNatural history of untreated primary hepatocellular carcinoma: a retrospective study of 157 patients . Am J Clin Oncol \n1998 ;21 :386–91 .9708639 \n[6] Tomanovic N Krstic A Brasanac D \nZygomatic bone metastasis as an initial presentation of hepatocellular carcinoma . Arch Iran Med \n2013 ;16 :675–8 .24206412 \n[7] Aoyama T Yoshikawa T \nTargeted therapy: Apatinib - new third-line option for refractory gastric or GEJ cancer . Nat Rev Clin Oncol \n2016 ;13 :268–70 .27071350 \n[8] Li J Qin S Xu J \nRandomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction . J Clin Oncol \n2016 ;34 :1448–54 .26884585 \n[9] Kong Y Sun L Hou Z \nApatinib is effective for treatment of advanced hepatocellular carcinoma . Oncotarget \n2017 ;8 :105596–605 .29285275 \n[10] Yu WC Zhang KZ Chen SG \nEfficacy and Safety of apatinib in patients with intermediate/advanced hepatocellular carcinoma: a prospective observation study . Medicine \n2018 ;97 :e9704.29505026 \n[11] Qin S \nApatinib in Chinese patients with advanced hepatocellular carcinoma: a phase II randomized, open-label trial . Asco Meeting Abstracts \n2014 ;32 15 suppl :\n[12] Lin S Hoffmann K Schemmer P \nTreatment of hepatocellular carcinoma: a systematic review . Liver Cancer \n2012 ;1 :144–58 .24159579 \n[13] Fong ZV Tanabe KK \nThe clinical management of hepatocellular carcinoma in the United States, Europe, and Asia: a comprehensive and evidence-based comparison and review . Cancer-Am Cancer Soc \n2014 ;120 :2824–38 .\n[14] Nordenstedt H White DL El-Serag HB \nThe changing pattern of epidemiology in hepatocellular carcinoma . Dig Liver Dis \n2010 ;42 :206–14 .\n[15] Okazaki N Yoshino M Yoshida T \nBone metastasis in hepatocellular carcinoma . Cancer-Am Cancer Soc \n1985 ;55 :1991–4 .\n[16] Attili VS Babu KG Lokanatha D \nBone metastasis in hepatocellular carcinoma: need for reappraisal of treatment . J Cancer Res Ther \n2008 ;4 :93–4 .18688127 \n[17] Chin A Liang TS Borislow AJ \nInitial presentation of hepatocellular carcinoma as a mandibular mass: case report and review of the literature . Oral Surg Oral Med Oral Pathol Oral Radiol Endod \n1998 ;86 :457–60 .9798231 \n[18] Reichbach EJ Levinson JD Fagin RR \nUnusual osseous metastases of hepatoma . JAMA \n1970 ;213 :2078–9 .4318255 \n[19] Neff BA Pribitkin EA Willcox TJ \nHepatocellular cancer metastatic to the zygoma: primary resection and immediate reconstruction . Ear Nose Throat J \n2002 ;81 :57–8 .11816393 \n[20] Bair MJ Lei WY Chen CL \nElectronic images of the month. An unusual presentation of hematemesis: a presentation of maxillary metastasis from hepatocellular carcinoma . Clin Gastroenterol Hepatol \n2010 ;8 :61–2 .\n[21] Kolarevic D Tomasevic Z Boricic I \nMetastasis of hepatocellular carcinoma presented as a tumor of the maxillary sinus and retrobulbar tumor . Vojnosanit Pregl \n2011 ;68 :359–62 .21627021 \n[22] Bhatia R Ravulapati S Befeler A \nHepatocellular carcinoma with bone metastases: incidence, prognostic significance, and management-single-center experience . J Gastrointest Cancer \n2017 ;48 :321–5 .28891006 \n[23] Huang HH Chang PH Fang TJ \nSinonasal metastatic hepatocellular carcinoma . Am J Otolaryngol \n2007 ;28 :238–41 .17606038 \n[24] Seong J Koom WS Park HC \nRadiotherapy for painful bone metastases from hepatocellular carcinoma . Liver Int \n2005 ;25 :261–5 .15780048 \n[25] Choi C Seong J \nPredictive factors of palliative radiotherapy response and survival in patients with spinal metastases from hepatocellular carcinoma . Gut Liver \n2015 ;9 :94–102 .25071067 \n[26] Llovet JM Ricci S Mazzaferro V \nSorafenib in advanced hepatocellular carcinoma . N Engl J Med \n2008 ;359 :378–90 .18650514 \n[27] Ding L Li QJ You KY \nThe use of apatinib in treating nonsmall-cell lung cancer: case report and review of literature . Medicine \n2016 ;95 :e3598.27196461 \n[28] Tian S Quan H Xie C \nYN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo . Cancer Sci \n2011 ;102 :1374–80 .21443688 \n[29] Kou P Zhang Y Shao W \nSignificant efficacy and well safety of apatinib in an advanced liver cancer patient: a case report and literature review . Oncotarget \n2017 ;8 :20510–5 .28103584 \n[30] Wei L Jin XL Chao Y \nComparison of efficacy between TACE combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma: a single-center randomized controlled trial . Cancer Biol Ther \n2017 ;18 :433.28548587 \n[31] Zhu H Zhao Y Wang X \nThe radiosensitive effect of apatinib for hepatocellular carcinoma patient with big paraspinal metastasis: a case report . Medicine \n2018 ;97 :e9598.29480860 \n[32] Zhu H Ma X Zhao Y \nThe excellent antitumor effect of apatinib alone as second-line therapy in a patient with sorafenib-refractory hepatocellular carcinoma: a case report . Medicine \n2018 ;97 :e11214.29924049\n\n", "fulltext_license": "CC BY-NC-ND", "issn_linking": "0025-7974", "issue": "98(18)", "journal": "Medicine", "keywords": null, "medline_ta": "Medicine (Baltimore)", "mesh_terms": "D006528:Carcinoma, Hepatocellular; D006801:Humans; D008113:Liver Neoplasms; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D016896:Treatment Outcome; D015050:Zygoma; D000509:alpha-Fetoproteins", "nlm_unique_id": "2985248R", "other_id": null, "pages": "e14595", "pmc": null, "pmid": "31045756", "pubdate": "2019-05", "publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review", "references": null, "title": "Zygomatic bone metastasis from hepatocellular carcinoma and the therapeutic efficacy of apatinib: A case report and literature review.", "title_normalized": "zygomatic bone metastasis from hepatocellular carcinoma and the therapeutic efficacy of apatinib a case report and literature review" }

[ { "companynumb": "CN-SA-2019SA154149", "fulfillexpeditecriteria": "1", "occurcountry": "CN", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "3", "drugadministrationroute": "041", "drugauthorizationnumb": "021492", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "135 MG, QCY", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATOCELLULAR CARCINOMA", "drugintervaldosagedefinition": "811", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "201612", "drugstartdateformat": "610", "drugstructuredosagenumb": "135", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "021492", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "METASTASES TO BONE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "METASTASES TO BONE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "GEMCITABINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATOCELLULAR CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE HYDROCHLORIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVOLEUCOVORIN CALCIUM" }, "drugadditional": "3", "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "300 MG, QCY", "drugenddate": null, "drugenddateformat": null, "drugindication": "METASTASES TO BONE", "drugintervaldosagedefinition": "811", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "201612", "drugstartdateformat": "610", "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CALCIUM LEVOFOLINATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVOLEUCOVORIN CALCIUM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATOCELLULAR CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CALCIUM LEVOFOLINATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "GEMCITABINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.6 G, QCY", "drugenddate": null, "drugenddateformat": null, "drugindication": "METASTASES TO BONE", "drugintervaldosagedefinition": "811", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "201612", "drugstartdateformat": "610", "drugstructuredosagenumb": "1.6", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE HYDROCHLORIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4.35 MG, QCY", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATOCELLULAR CARCINOMA", "drugintervaldosagedefinition": "811", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "201612", "drugstartdateformat": "610", "drugstructuredosagenumb": "4.35", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." } ], "patientagegroup": "5", "patientonsetage": "48", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Bone marrow failure", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LEI Q, CHEN H, ZHENG H, DENG F, WANG F, LI J ET AL.. ZYGOMATIC BONE METASTASIS FROM HEPATOCELLULAR CARCINOMA AND THE THERAPEUTIC EFFICACY OF APATINIB: A CASE REPORT AND LITERATURE REVIEW.. MEDICINE (BALTIMORE). 2019?98(18):E14595", "literaturereference_normalized": "zygomatic bone metastasis from hepatocellular carcinoma and the therapeutic efficacy of apatinib a case report and literature review", "qualification": "1", "reportercountry": "CN" }, "primarysourcecountry": "CN", "receiptdate": "20190618", "receivedate": "20190607", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16403708, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190711" } ]

{ "abstract": "Lewy body dementia (LBD) is asynucleinopathy that results in clinical manifestation of motor and neuropsychiatric symptoms. The disease burden associated with psychosis in LBD patients is significantly higher compared to other types of dementia or even to LBD without psychosis. Effective care management processes should include consideration of de-prescribing any offending agents including anticholinergics and dopaminergic agents, followed by nonpharmacological and low risk pharmacological approach. If addition of pharmacological agents is required, consideration should be given to acetylcholinesterase inhibitors, pimavanserin and atypical antipsychotics such as quetiapine or clozapine. Side effects of these medications should be considered prior to selection and initiation of a medication regimen. Goals of care and functional assessment are a crucial part of the optimized care plan, given overall guarded prognosis, in the context of numerous complications observed in this population. Palliative care consultation could facilitate symptom control and timely enrollment into hospice if consistent with patient's goals.", "affiliations": "Division of Geriatric Medicine and Gerontology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.;Division of Hospital Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA.;Division of Hospital Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA.;Division of Geriatric Medicine and Gerontology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.", "authors": "Badwal|Karun|K|;Kiliaki|Shangwe A|SA|;Dugani|Sagar B|SB|;Pagali|Sandeep R|SR|https://orcid.org/0000-0002-0838-1026", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1177/0891988720988916", "fulltext": null, "fulltext_license": null, "issn_linking": "0891-9887", "issue": null, "journal": "Journal of geriatric psychiatry and neurology", "keywords": "Lewy body dementia; Parkinson’s disease; pimavanserin; psychosis", "medline_ta": "J Geriatr Psychiatry Neurol", "mesh_terms": null, "nlm_unique_id": "8805645", "other_id": null, "pages": "891988720988916", "pmc": null, "pmid": "33461372", "pubdate": "2021-01-19", "publication_types": "D016428:Journal Article", "references": null, "title": "Psychosis Management in Lewy Body Dementia: A Comprehensive Clinical Approach.", "title_normalized": "psychosis management in lewy body dementia a comprehensive clinical approach" }

[ { "companynumb": "US-ALS-000712", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "QUETIAPINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "209497", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG AT BEDTIME", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product use in unapproved indication", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "24", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "QUETIAPINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBIDOPA\\LEVODOPA" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25-100 MG, 3 TABLETS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Behaviour disorder", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBIDOPA\\LEVODOPA" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ROPINIROLE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "3 TIMES DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Parkinson^s disease", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ROPINIROLE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVOTHYROXINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "88", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVOTHYROXINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "81", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ASPIRIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "QUETIAPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "209497", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product use in unapproved indication", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "QUETIAPINE" } ], "patientagegroup": "6", "patientonsetage": "77", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cerebral small vessel ischaemic disease", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Condition aggravated", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Badwal K., Kiliaki S.A., Dugani S.B., Pagali S.R. Psychosis Management in Lewy Body Dementia: A Comprehensive Clinical Approach. J Geriatr Psychiatry Neurol 2022; 35(3):255-61. doi:10.1177/0891988720988916.", "literaturereference_normalized": "psychosis management in lewy body dementia a comprehensive clinical approach", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20220428", "receivedate": "20220428", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20761994, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" } ]

{ "abstract": "OBJECTIVE\nHyponatraemia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a well-recorded adverse event observed in elderly patients on antidepressant treatment. Bupropion is an antidepressant agent usually reserved as an augmentation strategy for treatment-resistant depression. While hyponatraemia is not a documented side effect of bupropion, there are a few cases outside of Australia reported in the literature. We report on a case of hyponatraemia observed on bupropion initiation in a 70-year-old female patient with treatment-resistant depression. We present a discussion of the possible mechanism of action for the hyponatraemia observed in our case and prior reported cases.\n\n\nCONCLUSIONS\nOur case and review of the available literature highlights the dangers of polypharmacy in the management of treatment-resistant depression. Our findings suggest that the association of hyponatraemia with bupropion in our and subsequent cases was likely the result of medication interaction and not a direct side effect of bupropion. Where bupropion is being used as an augmenting agent in the treatment of depression we would suggest checking of serum sodium prior to commencement of bupropion, and monitoring thereafter. This is especially important in elderly patients where other risk factors for hyponatraemia are likely to be present.", "affiliations": "Psychiatry Registrar, North West Area Mental Health Service, Melbourne Health, Parkville, VIC, Australia drawiggins@gmail.com.;Aged Care Registrar, Western Health, Sunshine, VIC, Australia.;Old Age Psychiatrist, North West Aged Persons Mental Health Program, Melbourne Health, Broadmeadows, VIC, Australia.", "authors": "Wiggins|Aaron|A|;Balasubramanian|Thangam|T|;Ferraro|Angelo|A|", "chemical_list": "D000928:Antidepressive Agents; D016642:Bupropion; D015283:Citalopram; D004308:Dothiepin", "country": "England", "delete": false, "doi": "10.1177/1039856215597534", "fulltext": null, "fulltext_license": null, "issn_linking": "1039-8562", "issue": "23(5)", "journal": "Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists", "keywords": "adverse drug reaction; antidepressant; bupropion; elderly; hyponatraemia", "medline_ta": "Australas Psychiatry", "mesh_terms": "D000368:Aged; D000928:Antidepressive Agents; D016642:Bupropion; D015283:Citalopram; D003221:Confusion; D061218:Depressive Disorder, Treatment-Resistant; D004308:Dothiepin; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007010:Hyponatremia", "nlm_unique_id": "9613603", "other_id": null, "pages": "507-9", "pmc": null, "pmid": "26405241", "pubdate": "2015-10", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Hyponatraemia and confusion in a 70-year-old female when bupropion was added to dothiepin and escitalopram.", "title_normalized": "hyponatraemia and confusion in a 70 year old female when bupropion was added to dothiepin and escitalopram" }

[ { "companynumb": "AU-PRINSTON PHARMACEUTICAL INC.-2016PRN00038", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ASPIRIN." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "BUPROPION HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "202304", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 MG, ?PO MANE?", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPROPION HYDROCHLORIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "QUETIAPINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG, AT NIGHT", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "QUETIAPINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GLIPIZIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLIPIZIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN GLARGINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LANTUS" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ESCITALOPRAM OXALATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "30 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "30", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESCITALOPRAM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "225 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "225", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ESTRADIOL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESTRADIOL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "175 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "175", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WIGGINS A, BALASUBRAMANIAN T, FERRARO A. HYPONATRAEMIA AND CONFUSION IN A 70-YEAR-OLD FEMALE WHEN BUPROPION WAS ADDED TO DOTHIEPIN AND ESCITALOPRAM. AUSTRALAS PSYCHIATRY (DOI: 10.1177/1039856215597534). 2015?23(5):507-509", "literaturereference_normalized": "hyponatraemia and confusion in a 70 year old female when bupropion was added to dothiepin and escitalopram", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20160311", "receivedate": "20160311", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12173174, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20160526" }, { "companynumb": "AU-CIPLA LTD.-2017AU22984", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ESCITALOPRAM OXALATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESCITALOPRAM" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BUPROPION HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "206556", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPROPION HYDROCHLORIDE XL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Confusional state", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "WIGGINS A, BALASUBRAMANIAN T, FERRARO A. HYPONATRAEMIA AND CONFUSION IN A 70-YEAR-OLD FEMALE WHEN BUPROPION WAS ADDED TO DOTHIEPIN AND ESCITALOPRAM. AUSTRALAS PSYCHIATRY. 2015;23(5):507 TO 509", "literaturereference_normalized": "hyponatraemia and confusion in a 70 year old female when bupropion was added to dothiepin and escitalopram", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20171219", "receivedate": "20171219", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14299208, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AU-MYLANLABS-2016M1006967", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "ESTRADIOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESTRADIOL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN GLARGINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LANTUS" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "175MG", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOSULEPIN HYDROCHLORIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ASPIRIN /00002701/" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NORFLOXACIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "URINARY TRACT INFECTION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NORFLOXACIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ESCITALOPRAM OXALATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "077660", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "30 MG DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESCITALOPRAM" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "BUPROPION" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPROPION." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "QUETIAPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "AT NIGHT", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "QUETIAPINE" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "225MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOSULEPIN HYDROCHLORIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GLIPIZIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLIPIZIDE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Confusional state", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Akathisia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WIGGINS A, BALASUBRAMANIAN T, FERRARO A. HYPONATRAEMIA AND CONFUSION IN A 70-YEAR-OLD FEMALE WHEN BUPROPION WAS ADDED TO DOTHIEPIN AND ESCITALOPRAM. AUSTRALAS-PSYCHIATRY 2015?23(5):507-509.", "literaturereference_normalized": "hyponatraemia and confusion in a 70 year old female when bupropion was added to dothiepin and escitalopram", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20160222", "receivedate": "20160222", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12103098, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20160526" }, { "companynumb": "AU-ACCORD-034376", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "202392", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": [ { "drugrecuraction": "Hyponatraemia" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GLIPIZIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLIPIZIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NORFLOXACIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NORFLOXACIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ESCITALOPRAM OXALATE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "202389", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": [ { "drugrecuraction": "Hyponatraemia" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "30", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESCITALOPRAM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "BUPROPION HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "IN THE MRONING", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": [ { "drugrecuraction": "Hyponatraemia" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPROPION/BUPROPION HYDROCHLORIDE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PREVIOUSLY RECEIVED 225 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": [ { "drugrecuraction": "Hyponatraemia" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "175", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOSULEPIN HYDROCHLORIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ESTRADIOL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESTRADIOL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN GLARGINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LANTUS" }, { "actiondrug": null, "activesubstance": null, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "AT NIGHT", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "QUETIAPINE/QUETIAPINE FUMARATE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACETYLSALICYLIC ACID" } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Escherichia urinary tract infection", "reactionmeddraversionpt": "19.1", "reactionoutcome": null }, { "reactionmeddrapt": "Confusional state", "reactionmeddraversionpt": "19.1", "reactionoutcome": null }, { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WIGGINS A, BALASUBRAMANIAN T, FERRARO A. HYPONATRAEMIA AND CONFUSION IN A 70-YEAR-OLD FEMALE WHEN BUPROPION WAS ADDED TO DOTHIEPIN AND ESCITALOPRAM. AUSTRALAS PSYCHIATRY. 2015 OCT, 23(5):507-9", "literaturereference_normalized": "hyponatraemia and confusion in a 70 year old female when bupropion was added to dothiepin and escitalopram", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20161107", "receivedate": "20151012", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11618608, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20170206" }, { "companynumb": "AU-BAUSCH-BL-2016-004085", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN GLARGINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LANTUS" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ASPIRIN." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "175", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ESTROGENS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OESTRADIOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "BUPROPION" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "021515", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPROPION." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPONATRAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ESCITALOPRAM OXALATE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESCITALOPRAM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NORFLOXACIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NORFLOXACIN" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "QUETIAPINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "QUETIAPINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GLIPIZIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLIPIZIDE." } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Akathisia", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WIGGINS A, BALASUBRAMANIAN T, FERRARO A. HYPONATRAEMIA AND CONFUSION IN A 70-YEAR-OLD FEMALE WHEN BUPROPION WAS ADDED TO DOTHIEPIN AND ESCITALOPRAM.. AUSTRALAS PSYCHIATRY. 2015;23 (5):507-509.", "literaturereference_normalized": "hyponatraemia and confusion in a 70 year old female when bupropion was added to dothiepin and escitalopram", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20161031", "receivedate": "20160218", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12091208, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20170206" }, { "companynumb": "AU-IMPAX LABORATORIES, INC-2016-IPXL-00179", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "BUPROPION HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "075913", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "PROLONGED-RELEASE TABLET", "drugdosagetext": "75 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPROPION HYDROCHLORIDE SR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ESCITALOPRAM OXALATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "30 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "30", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESCITALOPRAM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ASPIRIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ESTROGENS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OESTRADIOL" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "225 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "225", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN HYDROCHLORIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GLIPIZIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLIPIZIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN HYDROCHLORIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 MG, 2 /DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NORFLOXACIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "URINARY TRACT INFECTION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NORFLOXACIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN GLARGINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LANTUS" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "175 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "175", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN HYDROCHLORIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WIGGINS A, BALASUBRAMANIAN T, FERRARO A.. HYPONATRAEMIA AND CONFUSION IN A 70-YEAR-OLD FEMALE WHEN BUPROPION WAS ADDED TO DOTHIEPIN AND ESCITALOPRAM. AUSTRALASIAN PSYCHIATRY. 2015?23(5):507-9", "literaturereference_normalized": "hyponatraemia and confusion in a 70 year old female when bupropion was added to dothiepin and escitalopram", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20160329", "receivedate": "20160329", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12219079, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160526" }, { "companynumb": "AU-EDGEMONT-2016EDG00007", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GLIPIZIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLIPIZIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ASPIRIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ESTRADIOL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESTRADIOL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN GLARGINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LANTUS" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "QUETIAPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG, AT NIGHT", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "QUETIAPINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "225 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "225", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ESCITALOPRAM OXALATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "30 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "30", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESCITALOPRAM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "BUPROPION" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "022497", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 MG, ^PO MANE^", "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPROPION." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "175 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "175", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WIGGINS A, BALASUBRAMANIAN T, FERRARO A. HYPONATRAEMIA AND CONFUSION IN A 70-YEAR-OLD FEMALE WHEN BUPROPION WAS ADDED TO DOTHIEPIN AND ESCITALOPRAM. AUSTRALAS PSYCHIATRY (DOI: 10.1177/1039856215597534). 2015?23(5):507-509", "literaturereference_normalized": "hyponatraemia and confusion in a 70 year old female when bupropion was added to dothiepin and escitalopram", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20160311", "receivedate": "20160311", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12171612, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20160526" }, { "companynumb": "AU-LUPIN PHARMACEUTICALS INC.-2016-00766", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ESCITALOPRAM OXALATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "078169", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "30 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIDEPRESSANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESCITALOPRAM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "BUPROPION" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPROPION." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "175", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GLIPIZIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLIPIZIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ASPIRIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "BUPROPION" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIDEPRESSANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPROPION." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ESTROGENS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OESTRADIOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIDEPRESSANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "225", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "QUETIAPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "AT NIGHT", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "QUETIAPINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ESCITALOPRAM OXALATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "078169", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESCITALOPRAM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN GLARGINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LANTUS" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL." } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WIGGINS A, BALASUBRAMANIAN T, FERRARO A. HYPONATRAEMIA AND CONFUSION IN A 70-YEAR-OLD FEMALE WHEN BUPROPION WAS ADDED TO DOTHIEPIN AND ESCITALOPRAM. AUSTRALASIAN PSYCHIATRY. 2015?23(5):507-509.", "literaturereference_normalized": "hyponatraemia and confusion in a 70 year old female when bupropion was added to dothiepin and escitalopram", "qualification": "1", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20160226", "receivedate": "20160226", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 12118092, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160526" }, { "companynumb": "AU-ACTAVIS PTY LTD-2016-03199", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACETYLSALICYLIC ACID" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "QUETIAPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG, QHS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "QUETIAPINE." }, { "actiondrug": "5", "activesubstance": null, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OESTRADIOL /00045401/" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ESCITALOPRAM OXALATE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNCONFIRMED", "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNK", "drugdosagetext": "30 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "30", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ESCITALOPRAM" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DECREASED TO 175 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "175", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "BUPROPION HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "077715", "drugbatchnumb": "UNCONFIRMED", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNK", "drugdosagetext": "75 MG PO MANE", "drugenddate": null, "drugenddateformat": null, "drugindication": "MAJOR DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUPROPION HYDROCHLORIDE (UNKNOWN)" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "DOTHIEPIN\\DOTHIEPIN HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "INCREASED TO 225 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "225", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOTHIEPIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNCONFIRMED", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNK", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL (UNKNOWN)" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METFORMIN HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METFORMIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN GLARGINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LANTUS" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NORFLOXACIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NORFLOXACIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "GLIPIZIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLIPIZIDE." } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WIGGINS A, BALASUBRAMANIAN T, FERRARO A. HYPONATRAEMIA AND CONFUSION IN A 70-YEAR-OLD FEMALE WHEN BUPROPION WAS ADDED TO DOTHIEPIN AND ESCITALOPRAM. AUSTRALAS PSYCHIATRY. 2015;23(5):507-9.", "literaturereference_normalized": "hyponatraemia and confusion in a 70 year old female when bupropion was added to dothiepin and escitalopram", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20160726", "receivedate": "20160218", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12089311, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20161109" } ]

{ "abstract": "We studied all patients at our institution with a diagnosis of multiple myeloma (MM), from 1 January 2004 to 1 July 2009, who received lenalidomide-dexamethasone (Rd) as initial therapy and had a time to progression of 72 months or longer. Of 240 patients, we identified 33 exceptional responders. Twenty-five patients received primary therapy with Rd and eight patients received Rd induction followed by early stem cell transplantation (SCT). Seven of the eight patients who received SCT did not receive maintenance therapy; one patient received 9 months of lenalidomide post transplant. Fifteen (45%) patients had known clonal plasma cell disorder before the diagnosis of MM. The dominant mode of clinical presentation was with lytic lesions in 28 patients. Of those with informative cytogenetics (n=24), trisomies were present in 19 (79%), including one patient with concurrent trisomies and t(11;14). Overall, 21 of 24 patients (88%) had either trisomies or t(11;14). None of these exceptional responders had high-risk cytogenetic features at baseline. Twenty-five patients (76%) had a complete response (CR), whereas eight patients (24%) achieved the exceptional response state without ever achieving a CR. We identify a cohort of exceptional responders to Rd-based therapy, representing ~10-15% newly diagnosed MM patients with normal renal function.", "affiliations": "Mayo Medical School, Mayo Clinic, Rochester, MN, USA.;Division of Hematology, Mayo Clinic, Rochester, MN, USA.;Division of Hematology, Mayo Clinic, Rochester, MN, USA.;Division of Hematology, Mayo Clinic, Rochester, MN, USA.;Division of Hematology, Mayo Clinic, Rochester, MN, USA.;Division of Hematology, Mayo Clinic, Rochester, MN, USA.;Division of Hematology, Mayo Clinic, Rochester, MN, USA.;Division of Hematology, Mayo Clinic, Rochester, MN, USA.", "authors": "Vu|T|T|;Gonsalves|W|W|;Kumar|S|S|http://orcid.org/0000-0001-5392-9284;Dispenzieri|A|A|;Lacy|M Q|MQ|;Buadi|F|F|;Gertz|M A|MA|;Rajkumar|S V|SV|", "chemical_list": "D000970:Antineoplastic Agents; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide", "country": "United States", "delete": false, "doi": "10.1038/bcj.2015.91", "fulltext": "\n==== Front\nBlood Cancer JBlood Cancer JBlood Cancer Journal2044-5385Nature Publishing Group bcj20159110.1038/bcj.2015.9126495860Original ArticleCharacteristics of exceptional responders to lenalidomide-based therapy in multiple myeloma Exceptional responders to lenalidomide-based therapyVu T 1Gonsalves W 2Kumar S 2http://orcid.org/0000-0001-5392-9284Dispenzieri A 2Lacy M Q 2Buadi F 2Gertz M A 2Rajkumar S V 2*1 Mayo Medical School, Mayo Clinic, Rochester, MN, USA2 Division of Hematology, Mayo Clinic, Rochester, MN, USA* Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. E-mail: rajkumar.vincent@mayo.edu10 2015 23 10 2015 1 10 2015 5 10 e363 11 09 2015 18 09 2015 Copyright © 2015 Macmillan Publishers Limited2015Macmillan Publishers LimitedThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/We studied all patients at our institution with a diagnosis of multiple myeloma (MM), from 1 January 2004 to 1 July 2009, who received lenalidomide–dexamethasone (Rd) as initial therapy and had a time to progression of 72 months or longer. Of 240 patients, we identified 33 exceptional responders. Twenty-five patients received primary therapy with Rd and eight patients received Rd induction followed by early stem cell transplantation (SCT). Seven of the eight patients who received SCT did not receive maintenance therapy; one patient received 9 months of lenalidomide post transplant. Fifteen (45%) patients had known clonal plasma cell disorder before the diagnosis of MM. The dominant mode of clinical presentation was with lytic lesions in 28 patients. Of those with informative cytogenetics (n=24), trisomies were present in 19 (79%), including one patient with concurrent trisomies and t(11;14). Overall, 21 of 24 patients (88%) had either trisomies or t(11;14). None of these exceptional responders had high-risk cytogenetic features at baseline. Twenty-five patients (76%) had a complete response (CR), whereas eight patients (24%) achieved the exceptional response state without ever achieving a CR. We identify a cohort of exceptional responders to Rd-based therapy, representing ~10–15% newly diagnosed MM patients with normal renal function.\n==== Body\nIntroduction\nMultiple myeloma (MM) is a plasma cell malignancy and part of a spectrum of clonal plasma cell disorders.1 The prognosis of MM varies dramatically based on host characteristics, stage, disease biology and response to therapy.2, 3, 4 Host characteristics that affect outcome include age, performance status, renal function and comorbidities.5 Stage provides a rough estimate of tumor burden and is assessed in MM using the Durie–Salmon Staging System6 and the International Staging System.7Disease biology is characterized by the underlying molecular cytogenetic classification of MM, as well as additional cytogenetic abnormalities that are acquired with clonal evolution.4 Thus, molecular subtypes translocation t (4;14), t 14;16 and 14;20 are associated with adverse prognosis; deletion 17p typically acquired during the course of disease progression is also associated with aggressive disease biology.3 Besides cytogenetic markers, disease biology can also be reflected by the presence of circulating plasma cells and lactate dehydrogenase levels. Recently, the Revised International Staging System has combined disease stage and biology, which often overlap into one prognostic system.8\n\nHost characteristics, stage and disease biology are known at baseline and can help with selection of therapy.2, 5 However, the fourth determinant of prognosis, response to therapy, is known only after therapy has already been administered. Several studies have examined the association between depth of response and outcome, as well as characteristics of patients with deep (complete) responses.9, 10, 11, 12 Of late, there is growing interest in identifying exceptional responders to therapy in terms of duration of response.13, 14, 15 Understanding the characteristics of exceptional responders to MM therapy can help us learn more about disease subtypes, biology and even identify new therapeutic strategies.\n\nLenalidomide is an important component of modern myeloma therapy, both in the frontline and relapsed refractory setting.16, 17 The goal of this study was to identify and characterize exceptional responders to lenalidomide-based initial therapy.\n\nPatients and methods\nWe identified all patients with a diagnosis of MM, from 1 January 2004 to 1 July 2009, who received lenalidomide–dexamethasone (Rd) as initial therapy for MM at Mayo Clinic, Rochester, MN, USA. We then identified patients with a time to progression (TTP) of 72 months or longer. This included patients who received Rd as primary therapy as well as patients who took Rd as induction and then proceeded to early (<12 months from diagnosis) autologous stem cell transplantation (SCT). Patients who stopped Rd because of any reason before progression (patient choice, physician choice, toxicity and soon) but resumed lenalidomide or Rd due to progression off therapy were also included in the cohort. Patients who received any other anti-MM drug and patients who underwent tandem transplantation during the 72 months following diagnosis were excluded. Patients with concomitant amyloidosis were excluded. Patients who received focal radiation to symptomatic sites at the time of diagnosis of MM were included only if the radiation was administered at the time of initial diagnosis before initiation of systemic therapy. The study was approved by the Institutional Review Board of the Mayo Clinic.\n\nThe electronic medical records, including demographic data, clinical notes, laboratory tests, imaging studies and pathologic reports were reviewed to verify therapy, response to treatment and to identify progression events. Relevant laboratory data including bone marrow plasma cell percentage, cytogenetics based on fluorescent in situ hybridization and conventional metaphase karyotyping, serum and urine M protein, free light chain ratio, hemoglobin, calcium and creatinine were abstracted for analysis from the electronic medical records and the MM clinical database at the Mayo Clinic.\n\nPatients were classified into the primary molecular subtypes of MM using the classification proposed by Kumar et al.4 Molecular classification was assessed by fluorescent in situ hybridization studies in all patients, except one patient in whom the classification of trisomies was made by baseline metaphase cytogenetics that showed hyperdiploidy and trisomies. All fluorescent in situ hybridization studies were performed for clinical purposes at the Mayo Clinic as previously described.18, 19 For molecular classification, categories were assigned regardless of when these abnormalities were detected in the course of the disease, including after therapy.20 Deletion 17p was only considered if it was present at initial diagnosis. Patients were considered to have high-risk disease if fluorescent in situ hybridization studies demonstrated one of the following abnormalities: t(4;14), t(14;16), t(14;20) or loss of p53 gene locus (del17p or monosomy 17).\n\nThe χ2-test was used to compare nominal values. TTP was measured from the date of diagnosis of MM until disease progression. Kaplan–Meier analysis was performed to generate progression and survival curves.\n\nResults\nOf 240 patients who were treated with Rd for newly diagnosed MM during the inclusion period for the study (155 primary Rd and 85 Rd induction followed by early SCT), we identified 33 exceptional responders (14%). Median follow-up was 85 months, range: 73–137 months. Most (23 patients) started therapy with low-dose dexamethasone; the remaining started with the pulsed high-dose dexamethasone regimen but decreased to low-dose dexamethasone after the initial few cycles. Two patients received radiation to one symptomatic site at the time of initial diagnosis. The International Staging System Stage was I in 15 patients, II in 14 patients, III in 3 patients and unevaluable in 1 patient. Durie–Salmon Stage was I in 1 patient, II in 11 patients and III in 21 patients. Detailed patient characteristics with respect to baseline clinical features and laboratory parameters are provided in Table 1.\n\nFifteen of 33 patients (45%) had a known clonal plasma cell proliferative disorder before the diagnosis of MM, including monoclonal gammopathy of undetermined significance (five patients), smoldering MM (four patients), solitary plasmacytoma (five patients) and two concurrent plasmacytomas (one patient). The dominant mode of presentation at diagnosis was with lytic lesions (28 patients), anemia (4 patients) and hypercalcemia (1 patient). None had extramedullary plasmacytomas at presentation.\n\nTwenty-seven patients (82%) had a measurable level of serum M protein (⩾1 g/dl). Among the six patients without a measurable serum M protein, five had free light chain-only type of MM. The remaining patient had an oligo-secretory IgA κ-MM. The serum M protein level was ⩾3 g/dl in 16 patients (48%) and ⩾4 g/dl in 9 patients (27%). In contrast, the urine M protein was ⩾2 g/24 h in only one patient; the involved serum free light chain level was <1000 mg/dl in all patients. Bone marrow plasma cell percentage was 60% in 12 patients (36%) and 80% in 2 patients (6%).\n\nTable 2 provides the molecular classification of MM based on cytogenetic studies performed on bone marrow examination in this cohort. Of those with informative cytogenetics (n=24), a hyperdiploidy/trisomy was present in 19 of 24 patients (79%) including the 1 patient with concurrent trisomies and t(11;14). The t(11;14) translocation was seen in three patients (8%). Overall, 21 of 24 patients (88%) had either trisomies or t(11;14). Isolated monosomy 13 (in the absence of any immunoglobulin heavy chain translocation or trisomy) was seen in 3 patients (8%). Of note, none of these exceptional responders had any high-risk cytogenetic features at baseline. Abnormalities on metaphase cytogenetics were seen in 4 of 27 patients (15%) on whom this test was done; in three patients the dominant abnormality was hyperdiploidy and the remaining patient had del 13q. When examined by the myeloma defining event at diagnosis, 19 of 20 patients (95%) with bone disease and informative cytogenetics had either trisomies or t(11;14). Of the 4 patients who presented with anemia as the myeloma defining event, 2 had isolated monosomy 13 and the other 2 had trisomies.\n\nThe response to therapy in this cohort is shown in Table 3 and represents the best response achieved anytime during therapy. Twenty-four patients (76%) had a complete response (CR); however, eight patients (24%) achieved the exceptional response state without ever achieving a CR, including three patients who only reached a partial response status and continued to have a measurable M protein. Among patients who achieved CR (n=25), the median time to CR was 15 months (range: 1–87 months); the time to CR was >12 months in 13 patients (52%) and >36 months in 5 patients (15%).\n\nThe exceptional responders could be classified into four groups (Table 4): primary therapy with Rd until progression (n=9), primary therapy with Rd but stopped treatment before progression (n=11), primary therapy with Rd stopped before progression and resumed later at first progression (n=5) and Rd induction followed by early SCT (n=8). None of the patients treated with Rd followed by early SCT received lenalidomide maintenance, except one patient who received lenalidomide for 9 months starting day 100 post transplant. No appreciable differences were noticed between the four groups based on the key baseline variables. However, the time to CR differed; median times were 6 months (primary Rd stopped therapy before progression), 14 months (primary therapy with Rd stopped before progression and resumed later at first progression), 15 months (Rd induction followed by early SCT) and 31 months (primary therapy with Rd until progression). Among patients who were in the primary Rd but stopped treatment before progression, the median duration of therapy was 37 months (range: 6–102 months); median TTP after stopping was 63 months.\n\nThree of the 33 patients have died. The cause of death was MM (2 patients) and unrelated infection (1 patient). The estimated 10-year survival rate was 85%. Twenty-three of 33 patients are alive and are progression free (69.7%), including 18 (54.5%) patients who can be considered disease free (sustained CR). Nine patients have progressed and one patient died without disease progression. Follow-up beyond the first progression event (which by definition would occur only after 72 months from initial diagnosis) is too short to analyze response to subsequent therapy. Among patients who progressed, the estimated post-progression 3-year survival rate was 89%.\n\nDiscussion\nIn this study we have identified and characterized a cohort of exceptional responders to lenalidomide-based therapy. We chose a TTP of 72 months, which is approximately three times the TTP expected with primary Rd.21 The presentation and distribution of several clinical features in exceptional responders (Table 1) appear to be similar to those seen in MM in general, including gender, hemoglobin concentration, monoclonal protein type, serum M protein concentration and bone marrow involvement.22 The proportion of patients with light-chain MM was also as expected, although overall urine M protein levels was ⩾2 g/dl in one patient and the serum involved free light chain levels were <1000 mg/dl in all patients. However, exceptional responders do appear to have some unique features of interest and represent the main findings of this study. First, a substantial proportion (45%) had a history of antecedent plasma cell disorder (monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM) or plasmacytoma), including plasmacytoma in six patients (18%). In a previous study at the Mayo Clinic, an antecedent plasma cell disorder was found in 34% of patients with MM and only 5% had a prior history of plasmacytoma.22 As all MM is preceded by a premalignant phase, the probability that an antecedent plasma cell disorder will be clinically detected will be proportionate to the duration spent in that phase. Thus, more indolent disease evolution with a longer premalignant course is more likely to be detected. Thus, our finding of a greater-than-expected number of patients with a known antecedent plasma cell disorder may indicate that exceptional responders have more favorable disease biology at baseline. In fact, Kyle et al.22 have shown that patients with a known history of MGUS and SMM before MM diagnosis have a better outcome than patients who present with de novo MM.\n\nSecond, most exceptional responders to Rd-based therapy had the trisomic type of MM (79%). The remaining had t(11;14) or isolated monosomy 13/del 13q. Trisomies generally constitute ~50% of MM4 and, hence, this finding suggests that patients with the trisomic form of MM are the ones in whom an exceptional response to Rd-based (or other immunomodulatory) therapy is likely to be seen. We have reported earlier that the trisomic form of MM is exquisitely sensitive to Rd23 and these data are consistent with that observation. None of the exceptional responders had high-risk cytogenetics. Although it is possible that this group is unlikely to have an exceptional response regardless of treatment strategy, it is possible that with other regimens such as bortezomib-based therapy a similar degree of exceptional response in patients with higher-risk cytogenetic categories, especially t(4;14) MM, may be possible.24\n\nThird, 85% of patients presented with bone disease as the myeloma defining event, including all but two patients with trisomies. We have previously noted that the more favorable prognosis of trisomic MM may be related to the fact that this subtype has a greater tendency towards bone disease and may thus be labeled as MM earlier than other subtypes, especially t(11;14) or t(4;14).25 Thus, early diagnosis and intervention may have had a role in the outcome of these patients and this needs further study.\n\nFourth, although most patients who stop Rd after a fixed duration of therapy will experience disease progression within a few months,21 there is a subset of patients who have an enduring response to Rd even after stopping therapy. In our study, among patients who took primary Rd and stopped early after a median duration of therapy of 3 years, the median TTP after stopping was ~5 years.\n\nFinally, it is important to note that achieving a CR or the rapidity of achieving CR was not essential to be an exceptional responder. Approximately 25% of patients were not in CR, including ~10% of patients who only achieved a partial response with therapy. This indicates that either the residual M protein is arising from a residual non-malignant monoclonal gammopathy of undetermined significance or that it represents a malignant clone that is not capable of proliferation due a microenvironment made inhospitable following therapy.26 In either event, this finding should raise some caution to the pursuit of minimal residual disease-negative state, as a proportion of patients may have excellent outcome even without achieving CR. The time to CR also appears to be slower in patients destined to be exceptional responders; median time to CR was 14 months and, more importantly, it was longer than 3 years in 15% of patients. Interestingly, it does appear that the speed at which CR is achieved influences in some way the treatment strategy, with patients who achieve CR sooner going off therapy before disease progression and those who have a slow response tending to stay on therapy until progression.\n\nNone of the patients in our cohort of exceptional responders had renal failure at presentation. Such patients may have been systematically excluded, because we do not initiate Rd-based therapy in patients with acute renal failure at diagnosis. However, none of the patients had even a mild elevation of serum creatinine indicates that exceptional responders to Rd-based therapy need to have normal renal function at baseline.\n\nIn summary, we identify a cohort of exceptional responders to Rd-based therapy, representing ~10–15% of newly diagnosed MM patients with normal renal function. Approximately 25% of exceptional responders achieved this status without achieving CR. These patients predominantly had the trisomic form of MM and presented with bone disease as their initial myeloma defining event; in such patients, the probability of being an exceptional respond to Rd is likely to be 25–30%. In an era of increasing therapeutic options for MM, these patients will probaby do exceedingly well even after disease progression on Rd. It is also possible that a proportion of these patients are even cured of their MM (residual M protein notwithstanding) with just one line of therapy. If we can accurately identify exceptional responders by biomarkers or genomic approaches, we can spare them the toxicity and costs of additional chemotherapeutic agents. Our next steps are to examine the trisomic form of MM in greater detail, to identify specific factors that will predict exceptional response to Rd-based therapy.\n\nThis work is supported in part by grants CA 107476 and CA 168762 from the National Cancer Institute, Rockville, MD, USA.\n\nAuthor contributions\n\nTV and SVR designed the research, analyzed the data, wrote and edited the manuscript. WG, SK, AD, MQL, FB and MAG participated in data interpretation, reviewed the manuscript and provided critical comments. All authors reviewed and approved the final manuscript.\n\nSK has obtained research support for clinical trials from Celgene, Millennium, Novartis, Janssen and Sanofi. AD has received research support for clinical trials from Pfizer, Jannsen, Millenium, Alnylam and Celgene. MAG has received research support from ISIS and Prothena, and honoraria from Celgene, Millennium Pharmaceuticals and Novartis. The remaining authors declare no conflict of interests.\n\nTable 1 Baseline characteristics\n \tPatients N=33\t\nAge, years, median (range)\t59 (32–78)\t\n Age <50 years, N (%)\t7 (21)\t\nFemale sex, N (%)\t12 (36)\t\nHemoglobin, median (range), g/dl\t11.5 (7.5–15.6)\t\n Hemoglobin <9 gm/dl, N (%)\t1 (9)\t\nSerum creatinine, median (range), mg/dl\t0.9 (0.6–1.3)\t\nSerum calcium, median (range), mg/dl\t9.7 (8.5–13)\t\n Calcium >11.0 mg/dl, N (%)\t2 (7)\t\nLactate dehydrogenase, median (range), mg/dl\t150 (95-206)\t\nBeta-2 microglobulin, median (range), μg/ml\t3.73 (1.37–10.9)\t\n Beta-2 microglobulin, >3.5 μg/ml\t17 (52)\t\n \t \t\nMonoclonal protein type\t \t\n IgG\t22 (67)\t\n IgA\t7 (21)\t\n \t \t\nFLC only\t4 (12)\t\nSerum monoclonal protein spike, median (range), g/dl\t2.8 (0.0–6.0)\t\n Serum monoclonal protein spike, >3.0 g/dl\t16 (48)\t\nUrine monoclonal protein spike, median (range), g/dl\t0.1 (0.0–4.7)\t\n Not present\t12 (36)\t\n Detected on immunofixation only\t4 (12)\t\n Measurable but <0.5 g/24 h\t12 (33)\t\n ⩾0.5 g/24 h\t5 (15)\t\nBMPC percentage, median (range)\t40 (2–90)\t\n BMPC >60%\t12 (36)\t\n \t \t\nSerum FLC assay\t \t\n Involved FLC, median (range), mg/dl\t10.2 (0.4–929)\t\n Involved/uninvolved ratio\t33.2 (0.938–1206.66)\t\n Involved/uninvolved FLC level⩾100 mg/dl\t6 (18)\t\n Involved/uninvolved FLC ratio⩾100\t9 (27)\t\nAbbreviations: BMPC, bone marrow plasma cell; FLC, free light chain.\n\nTable 2 Distribution of primary cytogenetic categories\nMolecular cytogenetic classification\tAll patients in whom cytogenetic studies were done (n=28)\tPatients with informative cytogenetic results (n=24)\t\n \tNo. of patients (%)\tNo. of patients (%)\t\nTrisomiesa\t19 (68)\t18 (75)\t\nt(11;14)(q13;q32)\t2 (7)\t2 (8)\t\nt(4;14)(p16;q32)\t0 (0)\t0 (0)\t\nMAF translocations [t(14;16)(q32;q23) and t(14;20)(q32;q11)]\t0 (0)\t0 (0)\t\nOther/unknown IgH translocation partner\t0 (0)\t0 (0)\t\nBoth IgH translocation and trisomiesb\t1(4)\t1 (4)\t\nMonosomy13/del(13q) in the absence of IgH translocation or trisomiesc\t3 (11)\t3 (13)\t\nNormal or insufficient plasma cells\t4 (14)\tNA\t\nAbreviations: FISH, fluorescent in situ hybridization; NA, not applicable.\n\nTrisomies were detected on baseline FISH studies in 18 of 19 patients (includes 1 patient with tetrasomy 11) and by metaphase cytogenetics in 1 patient.\n\nThis patient had t(11;14) and trisomies.\n\nIncludes one patient with concurrent monosomy 14.\n\nTable 3 Response to therapy\nResponse category\tPatients N=33\t\n \tN (%)\t\nComplete response\t25 (76)\t\nVery good partial response\t5 (15)\t\nPartial response\t3 (9)\t\nTable 4 Baseline characteristics and response according by treatment group\n \tPrimary Rd until progression (n=9)\tPrimary Rd stopped before progression (n=11)\tPrimary Rd stopped with progression and restarted (n=5)\tRd induction followed by SCT (n=8)\t\nAge, years, median (range)\t65 (36–70)\t60 (40–78)\t55 (32–75)\t62 (36–73)\t\nPrior plasma cell disorder, N\t6 (3 MGUS/SMM; 3 plasmacytoma)\t3 (3 MGUS/SMM)\t3 (2 MGUS/SMM; 1 plasmacytoma)\t3 (1 MGUS/SMM; 2 plasmacytoma)\t\nMDE at presentation\tBone, 8\nAnemia, 1\tBone, 10\nAnemia, 1\tBone, 3\nAnemia, 1\nHypercalcemia, 1\tBone, 7\nAnemia, 1\t\nMolecular classification, N\tTrisomies, 5\nt(11;14) 1t(11;14) plus trisomy, 1Isolated del 13, 1Normal/insufficient, 1\tTrisomies, 6t(11;14), 1\nNot done, 4\tTrisomies, 3\nNormal/insufficient, 1\nNot done, 1\tTrisomies, 4\nIsolated del 13, 2\nNormal/insufficient, 2\t\nBest response to therapy\tCR, 7\nVGPR, 2\tCR, 9\nVGPR, 1 PR, 1\tCR, 2\nVGPR, 2 PR, 1\tCR, 7\nPR, 1\t\nAbbreviations: CR, complete response; MDE, myeloma defining event; MGUS, monoclonal gammopathy of undetermined significance; Rd, lenalidomide–dexamethasone; SCT, stem cell transplantation; SMM, smoldering multiple myeloma.\n==== Refs\n1Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos M-V et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma . Lancet Oncol \n2014 ; 15 : e538 –e548.25439696 \n2Russell SJ, Rajkumar SV. Multiple myeloma and the road to personalised medicine . Lancet Oncol \n2011 ; 12 : 617 –619.21664869 \n3Mikhael JR, Dingli D, Roy V, Reeder CB, Buadi FK, Hayman SR et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013 . Mayo Clin Proc \n2013 ; 88 : 360 –376.23541011 \n4Kumar S, Fonseca R, Ketterling RP, Dispenzieri A, Lacy MQ, Gertz MA et al. Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics . Blood \n2012 ; 119 : 2100 –2105.22234687 \n5Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report . Blood \n2015 ; 125 : 2068 –2074.25628469 \n6Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival . Cancer \n1975 ; 36 : 842 –854.1182674 \n7Greipp PR, San Miguel JF, Durie BG, Avet-Loiseau H, Fonseca R, Jacobson JL et al. A New International Staging System (ISS) for Multiple Myeloma (MM) from the International Myeloma Working Group . Blood \n2003 ; 102 : A664 .\n8Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L et al. Revised International Staging System for multiple myeloma: a report from International Myeloma Working Group . J Clin Oncol \n2015 ; 33 : 2863 –2869.26240224 \n9Harousseau JL, Attal M, Avet-Loiseau H. The role of complete response in multiple myeloma . Blood \n2009 ; 114 : 3139 –3146.19638622 \n10Chanan-Khan AA, Giralt S. Importance of achieving a complete response in multiple myeloma, and the impact of novel agents . J Clin Oncol \n2010 ; 28 : 2612 –2624.20385994 \n11Harousseau JL, Palumbo A, Richardson PG, Schlag R, Dimopoulos MA, Shpilberg O et al. Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone . Blood \n2010 ; 116 : 3743 –3750.20628153 \n12Gay F, Larocca A, Wijermans P, Cavallo F, Rossi D, Schaafsma R et al. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients . Blood \n2011 ; 117 : 3025 –3031.21228328 \n13Printz C. NCI launches exceptional responders initiative: researchers will attempt to identify why some patients respond to treatment so much better than others . Cancer \n2015 ; 121 : 803 –804.25739575 \n14Sheridan C. Cancer centers zero in on exceptional responders . Nat Biotechnol \n2014 ; 32 : 703 –704.25101721 \n15Poh A. In search of exceptional responders . Cancer Discov \n2015 ; 5 : 8 .25583786 \n16Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial . Lancet Oncol \n2010 ; 11 : 29 –37.19853510 \n17Dimopoulos MA, Swern AS, Li JS, Hussein M, Weiss L, Nagarwala Y et al. Efficacy and safety of long-term treatment with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma . Blood Cancer J \n2014 ; 4 : e257 .25382609 \n18Fonseca R, Bailey RJ, Ahmann GJ, Rajkumar SV, Hoyer JD, Lust JA et al. Genomic abnormalities in monoclonal gammopathy of undetermined significance . Blood \n2002 ; 100 : 1417 –1424.12149226 \n19Fonseca R, Harrington D, Oken MM, Dewald GW, Bailey RJ, Van Wier SA et al. Biological and prognostic significance of interphase fluorescence in situ hybridization detection of chromosome 13 abnormalities in multiple myeloma: an Eastern Cooperative Oncology Group Study . Cancer Res \n2002 ; 62 : 715 –720.11830525 \n20Greenberg AJ, Rajkumar SV, Therneau TM, Singh PP, Dispenzieri A, Kumar SK. Relationship between initial clinical presentation and the molecular cytogenetic classification of myeloma . Leukemia \n2014 ; 28 : 398 –403.24005246 \n21Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma . N Engl J Med \n2014 ; 371 : 906 –917.25184863 \n22Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A et al. Review of 1,027 patients with newly diagnosed multiple myeloma . Mayo Clinic Proc \n2003 ; 78 : 21 –33.\n23Pandey S, Rajkumar SV, Kapoor P, Ketterling RP, Lacy MQ, Gertz MA et al. Impact of FISH abnormalities on response to lenalidomide in patients with multiple myeloma . ASH Annu Meeting Abstr \n2013 ; 122 : 3210 .\n24Bergsagel PL, Mateos MV, Gutierrez NC, Rajkumar SV, San Miguel JF. Improving overall survival and overcoming adverse prognosis in the treatment of cytogenetically high-risk multiple myeloma . Blood \n2013 ; 121 : 884 –892.23165477 \n25Rajkumar SV, Gupta V, Fonseca R, Dispenzieri A, Gonsalves WI, Larson D et al. Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma . Leukemia \n2013 ; 27 : 1738 –1744.23515097 \n26Bryant C, Suen H, Brown R, Yang S, Favaloro J, Aklilu E et al. Long-term survival in multiple myeloma is associated with a distinct immunological profile, which includes proliferative cytotoxic T-cell clones and a favourable Treg/Th17 balance . Blood Cancer J \n2013 ; 3 : e148 .24036947\n\n", "fulltext_license": "CC BY", "issn_linking": "2044-5385", "issue": "5()", "journal": "Blood cancer journal", "keywords": null, "medline_ta": "Blood Cancer J", "mesh_terms": "D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents; D003907:Dexamethasone; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma; D012074:Remission Induction; D013792:Thalidomide; D016896:Treatment Outcome", "nlm_unique_id": "101568469", "other_id": null, "pages": "e363", "pmc": null, "pmid": "26495860", "pubdate": "2015-10-23", "publication_types": "D016428:Journal Article; D052061:Research Support, N.I.H., Extramural", "references": "23165477;25101721;26240224;22234687;21664869;25628469;12528874;20385994;25739575;12149226;19853510;24036947;24005246;25583786;19638622;23515097;1182674;11830525;25184863;23541011;25439696;25382609;20628153;21228328", "title": "Characteristics of exceptional responders to lenalidomide-based therapy in multiple myeloma.", "title_normalized": "characteristics of exceptional responders to lenalidomide based therapy in multiple myeloma" }

[ { "companynumb": "US-CELGENE-USA-2015110733", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "LENALIDOMIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "021880", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULES", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "REVLIMID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Plasma cell myeloma", "reactionmeddraversionpt": "18.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "VU T. CHARACTERISTICS OF EXCEPTIONAL RESPONDERS TO LENALIDOMIDE-BASED THERAPY IN MULTIPLE MYELOMA.. BLOOD CANCER JOURNAL. 2015?5:363.", "literaturereference_normalized": "characteristics of exceptional responders to lenalidomide based therapy in multiple myeloma", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20151111", "receivedate": "20151111", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11723850, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160304" }, { "companynumb": "US-CELGENE-USA-2015110738", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "LENALIDOMIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "021880", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULES", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "REVLIMID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "021880", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Plasma cell myeloma", "reactionmeddraversionpt": "18.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "VU T. CHARACTERISTICS OF EXCEPTIONAL RESPONDERS TO LENALIDOMIDE-BASED THERAPY IN MULTIPLE MYELOMA.. BLOOD CANCER JOURNAL. 2015?5:E363:.", "literaturereference_normalized": "characteristics of exceptional responders to lenalidomide based therapy in multiple myeloma", "qualification": "5", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20151111", "receivedate": "20151111", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11723443, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160304" } ]

{ "abstract": "BACKGROUND\nFingolimod is a high-efficacy disease-modifying therapy for multiple sclerosis (MS) and was the first oral treatment approved for the disease. Adverse events include bradyarrhythmia, hypertension, macular oedema and increased risk of infections, mainly due to its main mechanism of action, the non-selective modulation of sphingosine-1-phosphate receptor.\n\n\nRESULTS\nWe report the baseline characteristics, effectiveness outcomes and adverse events of a prospective cohort of 177 patients with a median treatment duration of 24 months, in which four patients (2.3%) presented with otherwise non-provoked peripheral vascular events (PVE).\n\n\nCONCLUSIONS\nFurther studies are still needed to evaluate the frequency and severity of PVE in fingolimod patients.", "affiliations": "Neurology Department, Pontificia Universidad Católica de Chile, Chile.;Neurology Department, Pontificia Universidad Católica de Chile, Chile; Neurology Service, Hospital Dr. Sótero del Río, Chile. Electronic address: ethelciampi@gmail.com.;Neurology Department, Pontificia Universidad Católica de Chile, Chile; Neurology Service, Hospital Dr. Sótero del Río, Chile.;Neurology Department, Pontificia Universidad Católica de Chile, Chile; Neurology Service, Hospital Dr. Sótero del Río, Chile.;Neurology Department, Pontificia Universidad Católica de Chile, Chile.;Neurology Department, Pontificia Universidad Católica de Chile, Chile.;Neurology Department, Pontificia Universidad Católica de Chile, Chile.", "authors": "Pelayo|Carolina|C|;Ciampi|Ethel|E|;Uribe-San-Martín|Reinaldo|R|;Soler|Bernardita|B|;Reyes|Ana|A|;Vergara|Elizabeth|E|;Cárcamo|Claudia|C|", "chemical_list": "D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride", "country": "Netherlands", "delete": false, "doi": "10.1016/j.msard.2020.102411", "fulltext": null, "fulltext_license": null, "issn_linking": "2211-0348", "issue": "45()", "journal": "Multiple sclerosis and related disorders", "keywords": "Adverse events; Disease-modifying treatment; Fingolimod; Multiple sclerosis; Peripheral vascular events; Thrombosis", "medline_ta": "Mult Scler Relat Disord", "mesh_terms": "D015331:Cohort Studies; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents; D009103:Multiple Sclerosis; D020529:Multiple Sclerosis, Relapsing-Remitting; D011446:Prospective Studies", "nlm_unique_id": "101580247", "other_id": null, "pages": "102411", "pmc": null, "pmid": "32711299", "pubdate": "2020-10", "publication_types": "D016422:Letter", "references": null, "title": "Multiple sclerosis and related disorders: Short report peripheral vascular events in a real-world cohort of multiple sclerosis patients using Fingolimod.", "title_normalized": "multiple sclerosis and related disorders short report peripheral vascular events in a real world cohort of multiple sclerosis patients using fingolimod" }

[ { "companynumb": "NVSC2020CL219975", "fulfillexpeditecriteria": "1", "occurcountry": "CL", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "FINGOLIMOD HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "022527", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "MULTIPLE SCLEROSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2014", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GILENYA" } ], "patientagegroup": null, "patientonsetage": "36", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Renal artery dissection", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Thrombosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PELAYO C, CIAMPI E, URIBE SAN MARTIN R. MULTIPLE SCLEROSIS AND RELATED DISORDERS:SHORT REPORT PERIPHERAL VASCULAR EVENTS IN A REAL?WORLD COHORT OF MULTIPLE SCLEROSIS PATIENTS USING FINGOLIMOD. MULT SCLER RELAT DISORD. 2020?45:102411", "literaturereference_normalized": "multiple sclerosis and related disorders short report peripheral vascular events in a real world cohort of multiple sclerosis patients using fingolimod", "qualification": "3", "reportercountry": "CL" }, "primarysourcecountry": "CL", "receiptdate": "20200807", "receivedate": "20200807", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18125956, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "NVSC2020CL218756", "fulfillexpeditecriteria": "1", "occurcountry": "CL", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "FINGOLIMOD HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "022527", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "MULTIPLE SCLEROSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GILENYA" } ], "patientagegroup": null, "patientonsetage": "27", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Deep vein thrombosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PELAYO C, CIAMPI E, URIBE SAN MARTIN R. MULTIPLE SCLEROSIS AND RELATED DISORDERS:SHORT REPORT PERIPHERAL VASCULAR EVENTS IN A REAL?WORLD COHORT OF MULTIPLE SCLEROSIS PATIENTS USING FINGOLIMOD. MULT SCLER RELAT DISORD. 2020?45:102411", "literaturereference_normalized": "multiple sclerosis and related disorders short report peripheral vascular events in a real world cohort of multiple sclerosis patients using fingolimod", "qualification": "3", "reportercountry": "CL" }, "primarysourcecountry": "CL", "receiptdate": "20200806", "receivedate": "20200806", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18120575, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "NVSC2020CL218749", "fulfillexpeditecriteria": "1", "occurcountry": "CL", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "FINGOLIMOD HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "022527", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "MULTIPLE SCLEROSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GILENYA" } ], "patientagegroup": null, "patientonsetage": "40", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Retinal vein thrombosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PELAYO C, CIAMPI E, URIBE SAN MARTIN R. MULTIPLE SCLEROSIS AND RELATED DISORDERS:SHORT REPORT PERIPHERAL VASCULAR EVENTS IN A REAL?WORLD COHORT OF MULTIPLE SCLEROSIS PATIENTS USING FINGOLIMOD. MULT SCLER RELAT DISORD. 2020?45:102411", "literaturereference_normalized": "multiple sclerosis and related disorders short report peripheral vascular events in a real world cohort of multiple sclerosis patients using fingolimod", "qualification": "3", "reportercountry": "CL" }, "primarysourcecountry": "CL", "receiptdate": "20200806", "receivedate": "20200806", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18120765, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" } ]

{ "abstract": "A 67-year-old woman presented with bloody stools and constipation. A rectal digital examination revealed a smooth and elastic hard tumor in the posterior wall of the rectum. We diagnosed the tumor as rectal GIST measuring 5 cm in diameter. Because the patient desired anal preservation, neoadjuvant imatinib mesylate(IM)(400mg/day)treatment was administered. Although the diameter of the tumor reduced to 2 cm in the third week of administration, the patient experienced erythema-type drug eruption(Grade 3). We discontinued the IM treatment and initiated steroid therapy. After the eruption had disappeared, IM treatment was resumed, initially with half doses. Local transanal resection was performed 36days after the neoadjuvant IM treatment. Currently, the indication and the administration period of IM for preoperative treatment is not clear. It may be necessary to accumulate cases to evaluate neoadjuvant IM therapy.", "affiliations": "Dept. of Surgery, Kindai University Faculty of Medicine.", "authors": "Yoshioka|Yasumasa|Y|;Tokoro|Tadao|T|;Ushijima|Hokuto|H|;Daito|Koji|K|;Kawamura|Junichiro|J|;Ueda|Kazuki|K|;Hida|Jinichi|J|;Okuno|Kiyotaka|K|", "chemical_list": "D000970:Antineoplastic Agents; D000068877:Imatinib Mesylate", "country": "Japan", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0385-0684", "issue": "44(12)", "journal": "Gan to kagaku ryoho. Cancer & chemotherapy", "keywords": null, "medline_ta": "Gan To Kagaku Ryoho", "mesh_terms": "D000368:Aged; D001003:Anal Canal; D000970:Antineoplastic Agents; D005260:Female; D046152:Gastrointestinal Stromal Tumors; D006801:Humans; D000068877:Imatinib Mesylate; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D012004:Rectal Neoplasms", "nlm_unique_id": "7810034", "other_id": null, "pages": "1997-1999", "pmc": null, "pmid": "29394846", "pubdate": "2017-11", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "A Case of Local Resection for Rectal GIST Following Neoadjuvant Imatinib Mesylate Treatment.", "title_normalized": "a case of local resection for rectal gist following neoadjuvant imatinib mesylate treatment" }

[ { "companynumb": "JP-TEVA-2018-JP-900037", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "204285", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "GASTROINTESTINAL STROMAL TUMOUR", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMATINIB MESYLATE." } ], "patientagegroup": null, "patientonsetage": "67", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Rash erythematous", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "YOSHIOKA Y, TOKORO T, USHIJIMA H, DAITO K, KAWAMURA J, UEDA K, ET AL. [A CASE OF LOCAL RESECTION FOR RECTAL GIST FOLLOWING NEOADJUVANT IMATINIB MESYLATE TREATMENT]. GAN-TO-KAGAKU-RYOHO 2017?44(12):1997-1999.", "literaturereference_normalized": "a case of local resection for rectal gist following neoadjuvant imatinib mesylate treatment", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20180621", "receivedate": "20180531", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14957071, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" } ]

{ "abstract": "BACKGROUND\nProgressive multifocal leukoencephalopathy (PML) is a rapidly developing demyelinating disease in the cerebral white matter and is often caused by JC polyomavirus (JCV). PML after lung transplantation is rare and has a poor prognosis, with no established therapies. Reducing the patient's immunosuppressant doses, thereby restoring immunity, could be used to treat PML. However, some patients develop immune reconstitution inflammatory syndrome (IRIS) with this treatment, an immune-induced inflammatory response to JCV that results in serious neuronal damage. We herein report a case of a 60-year-old female who suffered from PML 5 years after lung transplantation, had worsened brain lesions thought to be related to PML-IRIS at the time of immunosuppressant reduction, and missed treatment opportunities.\n\n\nMETHODS\nA 60-year-old female developed PML 5 years after lung transplantation. Fluid-attenuated inversion recovery and diffusion-weighted brain magnetic resonance imaging (MRI) revealed multiple high-signal lesions, mainly in the cerebral white matter. Polymerase chain reaction found 0.32 million copies/mL of JCV in the cerebrospinal fluid. Thus, she was given a diagnosis of PML. Mycophenolate mofetil and tacrolimus dosages were reduced, and CD4-positive cell counts and the blood concentration of each immunosuppressant were monitored. Mefloquine was also orally administered at a daily dose of 275 mg for 3 days and was then administered at a dose of 275 mg per week. Although the patient's CD4-positive cell counts increased and her immune system recovered, her symptoms and brain MRI findings worsened. We suspected PML progression or a transition to PML-IRIS. Steroid pulse therapy to suppress the inflammatory lesions was not possible but was retrospectively indicated. The patient rapidly began to exhibit akinetic mutism and died 4 months after the onset of neurologic symptoms.\n\n\nCONCLUSIONS\nWhen neurologic symptoms and abnormal brain MRI findings are noted during immune recovery, it is often difficult to distinguish between progressed PML and PML-IRIS. However, the pathogenesis of brain lesions usually involves inflammation and immune-reactive mechanisms for JCV. Steroid pulse therapy, which can reduce inflammation, should thus be administered in organ transplantation cases with differential diagnoses including PML-IRIS.", "affiliations": "Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan. kazishii@md.tsukuba.ac.jp.;Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan.;Department of Pulmonology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan.;Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryomachi, Aoba-ku Sendai, 980-8575, Japan.;Department of Virology 1, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo, 162-8640, Japan.;Department of Virology 1, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo, 162-8640, Japan.;Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten'noudai, Tsukuba, Ibaraki, 305-8575, Japan.", "authors": "Ishii|Kazuhiro|K|http://orcid.org/0000-0003-2059-4670;Yamamoto|Fumiko|F|;Homma|Shinsuke|S|;Okada|Yoshinori|Y|;Nakamichi|Kazuo|K|;Saijo|Masayuki|M|;Tamaoka|Akira|A|", "chemical_list": "D007166:Immunosuppressive Agents", "country": "England", "delete": false, "doi": "10.1186/s12883-019-1493-1", "fulltext": "\n==== Front\nBMC NeurolBMC NeurolBMC Neurology1471-2377BioMed Central London 149310.1186/s12883-019-1493-1Case ReportProbable progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation: a case report and literature review http://orcid.org/0000-0003-2059-4670Ishii Kazuhiro +81-29-853-3224kazishii@md.tsukuba.ac.jp 1Yamamoto Fumiko fyamamoto-tuk@umin.ac.jp 1Homma Shinsuke s_homma@md.tsukuba.ac.jp 2Okada Yoshinori yoshinori-o@jcom.home.ne.jp 3Nakamichi Kazuo nakamich@nih.go.jp 4Saijo Masayuki msaijo@nih.go.jp 4Tamaoka Akira atamaoka@md.tsukuba.ac.jp 11 0000 0001 2369 4728grid.20515.33Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten’noudai, Tsukuba, Ibaraki, 305-8575 Japan 2 0000 0001 2369 4728grid.20515.33Department of Pulmonology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Ten’noudai, Tsukuba, Ibaraki, 305-8575 Japan 3 0000 0001 2248 6943grid.69566.3aDepartment of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryomachi, Aoba-ku Sendai, 980-8575 Japan 4 0000 0001 2220 1880grid.410795.eDepartment of Virology 1, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640 Japan 31 10 2019 31 10 2019 2019 19 26329 10 2018 9 10 2019 © The Author(s). 2019Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background\nProgressive multifocal leukoencephalopathy (PML) is a rapidly developing demyelinating disease in the cerebral white matter and is often caused by JC polyomavirus (JCV). PML after lung transplantation is rare and has a poor prognosis, with no established therapies. Reducing the patient’s immunosuppressant doses, thereby restoring immunity, could be used to treat PML. However, some patients develop immune reconstitution inflammatory syndrome (IRIS) with this treatment, an immune-induced inflammatory response to JCV that results in serious neuronal damage. We herein report a case of a 60-year-old female who suffered from PML 5 years after lung transplantation, had worsened brain lesions thought to be related to PML-IRIS at the time of immunosuppressant reduction, and missed treatment opportunities.\n\nCase presentation\nA 60-year-old female developed PML 5 years after lung transplantation. Fluid-attenuated inversion recovery and diffusion-weighted brain magnetic resonance imaging (MRI) revealed multiple high-signal lesions, mainly in the cerebral white matter. Polymerase chain reaction found 0.32 million copies/mL of JCV in the cerebrospinal fluid. Thus, she was given a diagnosis of PML. Mycophenolate mofetil and tacrolimus dosages were reduced, and CD4-positive cell counts and the blood concentration of each immunosuppressant were monitored. Mefloquine was also orally administered at a daily dose of 275 mg for 3 days and was then administered at a dose of 275 mg per week. Although the patient’s CD4-positive cell counts increased and her immune system recovered, her symptoms and brain MRI findings worsened. We suspected PML progression or a transition to PML-IRIS. Steroid pulse therapy to suppress the inflammatory lesions was not possible but was retrospectively indicated. The patient rapidly began to exhibit akinetic mutism and died 4 months after the onset of neurologic symptoms.\n\nConclusions\nWhen neurologic symptoms and abnormal brain MRI findings are noted during immune recovery, it is often difficult to distinguish between progressed PML and PML-IRIS. However, the pathogenesis of brain lesions usually involves inflammation and immune-reactive mechanisms for JCV. Steroid pulse therapy, which can reduce inflammation, should thus be administered in organ transplantation cases with differential diagnoses including PML-IRIS.\n\nKeywords\nProgressive multifocal leukoencephalopathyMefloquineCD4 positive cellJC polyomavirusLung transplantationImmune reconstitution inflammatory syndromehttp://dx.doi.org/10.13039/501100001691Japan Society for the Promotion of Science17K09768Nakamichi Kazuo http://dx.doi.org/10.13039/501100003478Ministry of Health, Labour and WelfareH29-Nanchitou (Nan)-Ippan-036Nakamichi Kazuo issue-copyright-statement© The Author(s) 2019\n==== Body\nBackground\nProgressive multifocal leukoencephalopathy (PML) is a rare, progressive demyelinating disease of the brain, caused by reactivation of JC polyomavirus (JCV) in glial cells, especially in the white matter. A diagnosis of PML requires identification of JCV via polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) samples or via in situ hybridization of brain biopsy tissues [1]. PML is a critical and lethal CNS complication that often follows the kidney, liver, heart, lung, or bone marrow transplantation [2]. PML after lung transplantation is rarely reported, with only seven cases documented in the literature [2–7]. Treatment for PML is challenging and includes the use of mefloquine, cidofovir, and cytarabine, which inhibit JCV replication. Mirtazapine, a 5-HT2a receptor inhibitor that prevents the spread of JCV infections to oligodendrocytes, is also used in the treatment of PML [8]. In addition, the progression of PML may be interfered with immune recovery, particularly in cases where the use of immunosuppressants can be safely reduced or discontinued without causing organ rejection.\n\nPML treatments are limited at present, and conventional therapies, such as mirtazapine, cidofovir, cytarabine, and mefloquine, are not effective and have side effects [8]. For instance, some treatments use passive and active immunization. Passive immunization utilizes recombinant human anti-JCV VP-1 monoclonal antibodies to neutralize JCV in the blood or central nervous system. A JCV-specific cytotoxic T lymphocyte may be generated by peripheral blood mononuclear cells from a stem cell donor, which may be stimulated with JCV VP-1 and large T antigens [9]. Therefore, innovative and useful treatments are urgently needed for PML.\n\nImmune reconstitution inflammatory syndrome occurring after PML (PML-IRIS) is the inflammatory reaction that occurs near PML lesions when immunocompetence is recovered. Clinical symptoms and brain magnetic resonance imaging (MRI) findings often worsen in PML-IRIS. Recently, attempts have been made to differentiate PML-IRIS from progressed PML via serial gadolinium-enhanced MRI and T2-weighted images. However, it is still difficult to distinguish between these two diagnoses in many cases [10].\n\nWe herein present a case of a 60-year-old female who suffered from PML 5 years after lung transplantation, had aggravated brain lesions thought to be related to PML-IRIS at the time of immunosuppressive dose reduction, and missed the treatment opportunity.\n\nCase presentation\nThe patient was a 60-year-old female who visited our hospital because of progressive apathy. She was previously diagnosed with pulmonary lymphangioleiomyomatosis at 42 years of age and underwent a right lung transplant at 55 years of age. After transplantation, oral tacrolimus (1.9 mg), mycophenolate mofetil (MMF; 500 mg), and prednisolone (5 mg) were prescribed. She did not undergo post-operative home oxygen therapy and was able to perform housework without any problems. Three months before her hospitalization, the patient experienced dizziness, decreased motivation and activity, confabulations, and delusions. She received an influenza vaccination 6 weeks before her admission. Three weeks before her hospitalization, the patient began to make medication administration errors and experience urinary incontinence.\n\nShe was suspected by our hospital physician of having a neurological disorder and thus underwent brain MRI, and T2-weighted and fluid-attenuated inversion recovery (FLAIR) images revealed multiple, high-signal lesions in the white matter in the bilateral cerebral hemispheres. Based on these findings, the patient was admitted in our hospital.\n\nFurther examinations found that the patient was conscious but apathetic, with poor spontaneous speech. She had no cranial nerve abnormalities. Her tendon reflexes were generally exaggerated, and her Babinski reflex elicited plantar flexion without paralysis. The patient had no clear sensory impairments, cerebellar ataxia, autonomic nervous system disorders, or meningeal irritation. No abnormalities were noted in her physical examination.\n\nBlood tests revealed leukopenia (2700/μL), anemia (9.0 g/dL), low CD4-positive lymphocytes (242/μL), hypo-γ-globulinemia (IgG 683 mg/dL), and mild renal dysfunction. Her thyroid function, glucose tolerance, and vitamin B1 and B12 levels were normal. The levels of tumor markers, including CA-19-9, CA 125, and CEA, were not elevated. No autoantibodies that could cause cerebrovasculitis were detected. Serum RPR, TPHA, anti-HBsAg, anti-HCV antibody, anti-HIV antibody, anti-HTLV-1 antibody, and interferon-gamma release assays such as the T-SPOT® were negative. CSF examinations, including cell counts, cell type, protein level, and glucose and chloride levels, were normal. β-D-glucan (< 6.0 pg/mL), sIL -2R (< 50 U/mL), myelin basic protein, and oligoclonal bands were all negative. In addition, CSF viral PCR and RT-PCR were negative for the varicella-zoster virus, herpes simplex virus types 1 and 2, human herpesviruses 6 and 7, cytomegalovirus, adenovirus DNA, and measles virus RNA. However, CSF PCR for JCV, performed at the National Institute of Infectious Diseases, was positive (0.32 million copies per mL).\n\nBrain MRI on the patient’s eighth day of hospitalization revealed high-intensity lesions on both T2-weighted and FLAIR imaging in the cerebral white matter in the bilateral frontal lobes. These lesions were enlarged relative to those observed on the patient’s initial MRI at admission. These same lesions appeared on high-intensity diffusion-weighted imaging (DWI) and low-intensity T1-weighted imaging (Fig. 1). No abnormal accumulation was detected using brain thallium scintigraphy. The patient’s electroencephalogram was within the normal range, and no epileptiform discharge was noted.\nFig. 1 Imaging findings of this patient. a Chronological changes in brain magnetic resonance imaging (MRI), fluid attenuated inversion recovery (FLAIR; top row), and diffusion weighted imaging (DWI, bottom row) on an axial view. Eight days following the patient’s admission, a FLAIR image revealed a high signal lesion in the cerebral white matter, which was dispersed in the central bilateral frontal lobes. Signal elevations were also revealed on DWI. (left) Twenty-five days following the patient’s admission, the number of high signal white matter lesions increased on FLAIR and DWI, and the discrete lesions expanded. (middle) Fifty days following the patient’s admission, the lesion with an elevated FLAIR signal expanded further to cover the entire bilateral frontal lobes. On DWI, the patient’s lesions had altered signal facilitation in the center and a restricted signal along the edge with perilesional edema. (right). b T2-weighted magnetic resonance (MR) images (top row) demonstrated signal changes in the perivascular lesion. T1-weighted magnetic resonance imaging with contrast administration 25 days following the patient’s admission revealed enhanced vasculature (likely veins). (white arrow) Subsequently, a T2-weighted image taken 50 days after the patient’s admission revealed perivascular edema around the indicated blood vessel. (white arrowhead) Similar perivascular edema was identified in nearby blood vessels.\n\n\n\nBecause the patient had a compromised immune system owing to use of several immunosuppressant drugs following her lung transplantation, differential diagnoses were considered, including PML, viral encephalopathy, delayed graft versus host disease vasculitis, tacrolimus encephalopathy, and lymphoproliferative disease. Acute disseminated encephalomyelitis (ADEM) was also suspected due to the patient’s post-vaccination status.\n\nAs shown in Fig. 2, because the result of HSV-PCR of the CSF sample was negative, administration of acyclovir was discontinued 5 days after the patient’s admission. Brain MRI performed 25 days after the patient’s admission confirmed the enlargement of white matter lesions in the bilateral frontal lobes and revealed a faint gadolinium contrast effect in the left frontal lesion. At this time, the patient’s CSF was found to be positive for JCV-DNA. Given her brain MRI findings, she was diagnosed with probable PML.\nFig. 2 Clinical course. Mycophenolate mofetil (500 mg) and tacrolimus (1.9 mg) were administered after the patient was released from the hospital. The patient’s excess apathy was noted 5 years after her lung transplant. This patient was admitted in our hospital 1 month after onset of apathy. Herpes encephalitis and acute disseminated encephalomyelitis were suspected at first. Accordingly, acyclovir and steroid pulse therapies were administered but were ineffective. Furthermore, JC polyoma virus (JCV)-PCR revealed transcript concentrations of 0.32 million copies/mL in the cerebrospinal fluid. Given these findings and those from magnetic resonance imaging (MRI), the patient was diagnosed with progressive multifocal leukoencephalopathy. Immunosuppressant drug levels were reduced, and an acute rejection episode was monitored via CD4-positive cell counts. Mefloquine treatment was also started. Although this patient’s CD4-positive cell counts gradually increased, her clinical symptoms progressed. She exhibited akinetic mutism 1 month after hospitalization (2 months after onset of PML). Despite increased CD4-positive cell counts, JCV-PCR copy numbers in the cerebrospinal fluid did not decrease, and her symptoms did not improve. Three months after her initial hospitalization (4 months after symptom onset), the patient died due to PML-related complications\n\n*Brain MRI performed on admission; **Brain MRI performed 25 days after admission; ***Brain MRI performed 50 days after admission.\n\n\n\nThe patient’s tacrolimus and MMF immunosuppressant dosages were respectively reduced from 1.9 to 0.5 mg and from 500 to 250 mg in 5 weeks. At the same time, mefloquine (275 mg/day) was administered for 3 days as a therapeutic agent according to the Japanese PML practice guidelines. Its use had been reported previously for PML after lung transplantation [2, 5] (Table 1). Following immunosuppressant dosage reductions, the patient’s CD4-positive lymphocyte levels, an indicator of immunosuppression, gradually increased. However, brain MRI performed 50 days after the patient’s admission revealed that the patient’s lesions had expanded and swelled due to a mass effect [10]. The enlarged lesion had a low central signal intensity on DWI but a high signal intensity along its periphery (Fig. 1) [11, 12]. Although the patient’s CD4-positive cell counts further recovered 81 days after the patient’s admission, CSF JCV levels increased to 0.38 million copies/mL. The patient regrettably died due to PML-related complications 91 days after her admission.\nTable 1 Clinical features of the past reported cases that developed PML after lung transplantation\n\nCase (year)\tAge\n/Sex\tImmuno-\nSuppressant regimen\tTime to PML onset from transplantation (Mo)\tClinical\nSymptoms\tMethod of diagnosis\n(specimen)\tReduced immunosupressant as therapy\tTreatment for PML\tFrom PML onset to diagnosis (Mo)\tOutcome (cause of death/ period from onset to death; Mo)\t\nOuwens JP\n\n (2000) [3]\n\n\t43/M\tAZA\n\nCsA\n\nCS\n\n\t15\tVisual loss, seizure, visual hallucination, ataxia, rt.paresis, dysarthria, memory impairment\tPCR (CSF)\tRD\n\nChange\n\n(AZA→MMF→CsA)\n\n\t-\t13\tDied (PML / 15)\t\nWaggoner J\n\n(2009) [4]\n\n\t38/F\tAZA,Tac, CS,Alemtuzumab,\t43\tGait instability (ataxia)\n\nVisual changes, confusion\n\n\tPCR (CSF)\tRD\tcidofovir\n\nmirtazapine\n\n\t1.5 ~ 2\tDied (respiratory failure / 5)\t\nMateen FJ\n\n(2011) [2]\n\n\t39/F\t-\t42\tAtaxia\tPCR (CSF)\tRD\tmirtazapine,\n\nmefloquine\n\n\t3\tDied (ND / 9.1)\t\nMateen FJ\n\n(2011) [2]\n\n\t62/F\t-\t27\tMemory impairment, Ataxia, lt. hemiparesis\tPCR (CSF)\tRD\t-\t< 1\tDied (ND /15.6)\t\nLobo LJ\n\n (2013) [5]\n\n\t61/M\tRituximab\n\nCsA\n\nMMF\n\nCS\n\n\t13\tHeadache, Malaise\n\nMemory impairment\n\n\tPCR (CSF)\tRD\t-\tND\tNeurologic symptoms exacerbation, move to hospice\t\nMoua T\n\n(2013) [6]\n\n\t61/M\tTac\n\nCS\n\n\t5\tRt. Hemiparesis & sensory disturbance, cognitive decline, aphasia\tISH (brain biopsy)\tRD\tcytarabine\t3\tDied (ARE?/ 7)\t\nPanchabhai TS (2016) [7]\t60/F\tTac\n\nCS\n\n\t16\tLt. arm paresis, Memory impairment, visual deficits, emotional lability,\tPCR (BALF & CSF)\tChange (Tac→rapamycin), Discontinued\t-\t2\tDied (respiratory failure: ARE / 3)\t\nPresent case\t60/F\tTac\n\nMMF\n\nCS\n\n\t61\tApathy\tPCR (CSF)\tRD\tmefloquine\t2\tDied (respiratory failure / 5)\t\nAZA Azathioprine, CsA Cyclosporine, CS Corticosteroid, Tac Tacrolimus, MMF Mycophenolate mofetil, CSF Cerebrospinal fluid, PCR Polymerase chain reaction, ISH In-situ hybridization, BALF Bronchoalveolar lavage fluid, RD Reduced doses, ND Not described, ARE Acute rejection episode,\n\n\n\nDiscussion and conclusions\nTo date, seven cases of PML that occurred following lung transplantation have been reported in the literature [2–7]. In these cases, different immunosuppressive drugs were used at PML onset, and more than two immunosuppressants were administered in each case. Some cases occurred after intensive immunosuppression therapy or administration of alemtuzumab, rituximab, or steroid pulse therapy, which was used due to graft rejection. Tacrolimus was used in the present case, as well as in three out of the seven cases. Up to the present, no studies have suggested a relationship between tacrolimus use and PML.\n\nNotably, the patient in the study by Shitrit et al. was diagnosed with PML following brain biopsy, and the causative virus was BK virus rather than JCV. The effectiveness of cidofovir and its therapeutic reactivity can be different in PML with the presence of JCV [13]. We thus eliminated this case from our literature review (Table 1). The literature review included one case of mefloquine and mirtazapine use, [2] one case of cidofovir and mirtazapine use, [4] one case of cytarabine alone, [6] and three untreated cases [2, 3, 7] of PML after lung transplantation. (Table 1) Because cases of PML after organ transplantation are rare, this literature review provides a significant summary of published cases of PML after organ transplantation.\n\nSeveral studies showed that decreasing immunosuppressant usage led to preferable outcomes. In fact, in the included studies, all survivors of PML reduced or discontinued immunosuppressant use to restore their immunity against JCV, regardless of whether anti-JCV therapy was administered [14–18]. Of the seven post-lung-transplantation PML patients, five had immunosuppressant reductions or discontinuation [2, 4–6], and two underwent treatment with other immunosuppressants (Table 1) [3, 7]. However, few reports have identified useful indicators for immunosuppressant reductions [4].\n\nAccumulating evidence indicates that CD4 is not an indicator of PML, and PML can develop at any CD4 level, although low CD4 cell counts are often associated with the risk of PML. In a case investigated by Waggoner et al., PML developed 1 year after treatment with alemtuzumab (CD4-positive cell count: 41/μL). Despite a decreased immunosuppressant dose, this patient’s CD4-positive cell count increased to 162/μL, indicating PML progression [4]. Conversely, in another case of PML after liver transplantation, discontinuation of an immunosuppressant led to increased CD4-positive cells (648/μL), and with mefloquine treatment and immunosuppressant reduction, both lesion expansion and neurologic symptom progression halted [19]. Therefore, increased CD4 cell counts may serve as a marker of immune reconstitution.\n\nPML-IRIS is characterized by an exacerbation of neurologic symptoms despite partial or full immune recovery and previously immunocompromised status. Clinically differentiating between PML and PML-IRIS is often difficult. Attempts have been made to distinguish between these conditions using sequential differences in brain MRI findings, and further identification of different inflammatory patterns using MRI is expected [10]. Brain MRI findings, including new swelling with perilesional and perivascular edema, are often consistent in PML-IRIS cases. Sequential gadolinium enhancement MRI may be used in some cases to further identify imaging abnormalities, although this approach was not used in the present case because of the patient’s pre-existing renal dysfunction. Most importantly, despite the recovery of CD4 positive cell counts, neurological symptoms and brain MRI findings were exacerbated in the present case. Therefore, a diagnosis of PML-IRIS was strongly suspected upon retrospective consideration. If steroid pulse therapy had been administered at the time of symptom onset or upon discovery of worsening brain MRI findings, this patient might have survived longer. Critically, JCV levels may not necessarily reflect the progression of PML in the advanced stage [20].\n\nActive immunization has been proposed for the treatment of PML, and the JCV vaccine can be used to prevent PML development by boosting JCV VP1 antigen levels using recombinant interleukin-7 [21] or JCV peptide antigens inoculated via the intestinal tract [8]. Recently, pembrolizumab or nivolumab, which block PD-1 suppressing JCV clearance, have been demonstrated to effectively treat PML [22, 23]. In addition, injection of allogeneic BK virus-specific T cells may also be effective for treating PML and controlling IRIS [24]. However, these treatments have limited efficacy and severe side effects. Therefore, further studies are needed to develop highly safe therapeutic agents that directly inactivate JCV.\n\nIn conclusion, PML after lung transplantation under the conditions described above has a poor prognosis. PML treatment must allow the patient’s immune system to recover sufficiently so that he/she can combat PML without sacrificing organs required for life. Distinguishing IRIS from PML may be difficult; however, once immune reconstitution is underway, treatment for suspected IRIS, which has been demonstrated to be beneficial in some circumstances, should be administered when the conditions are similar to those in the present case.\n\nAbbreviations\nADEMAcute disseminated encephalomyelitis\n\nDWIDiffusion weighted image\n\nFLAIRFluid-attenuated inversion recovery\n\nIRISImmune reconstitution inflammatory syndrome\n\nJCVJC polyoma virus\n\nMMFMycophenolate mofetil\n\nMRIMagnetic resonance imaging\n\nPCRPolymerase chain reaction\n\nPMLProgressive multifocal leukoencephalopathy\n\nTacTacrolimus\n\nPublisher’s Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n\nKazuhiro Ishii and Fumiko Yamamoto contributed equally to this work.\n\nWe would like to thank Editage (www.editage.jp) for English language editing.\n\nAuthors’ contributions\nKI, SH, YO, and AT collected and interpreted the clinical data. KN and MS completed JCV-PCR analyses. KI and FY wrote the manuscript and prepared the Figs. KI and FY contributed equally to this work. All authors critically revised and approved the manuscript.\n\nFunding\nThis work was partly supported by JSPS KAKENHI (Grant Number 17 K09768) and by a Grant-in-Aid for the Research Committee of Prion Disease and Slow Virus Infection, Research on Policy Planning and Evaluation for Rare and Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan (Grant Number H29-Nanchitou (Nan)-Ippan-036).\n\nAvailability of data and materials\nData generated during this study are included in this published article.\n\nEthics approval and consent to participate\nNot applicable.\n\nConsent for publication\nWritten informed consent for publication of the clinical details and clinical images was obtained from this patient’s husband. A copy of the consent form is available for review by the Editor of this journal.\n\nCompeting interests\nThe authors declare that they have no competing interests.\n==== Refs\nReferences\n1. Vago L Cinque P Sala E Nebuloni M Caldarelli R Racca S JCV-DNA and BKV-DNA in the CNS tissue and CSF of AIDS patients and normal subjects. Study of 41 cases and review of the literature J Acquir Immune Defic Syndr Hum Retrovirol 1996 12 139 146 10.1097/00042560-199606010-00006 8680884 \n2. Mateen FJ Muralidharan R Carone M van de Beek D Harrison DM Aksamit AJ Progressive multifocal leukoencephalopathy in transplant recipients Ann Neurol 2011 70 305 322 10.1002/ana.22408 21823157 \n3. Ouwens JP Haaxma-Reiche H Verschuuren EA Timens W Steenhuis LH de Boer WJ Groningen lung transplant group. Visual symptoms after lung transplantation: a case of progressive multifocal leukoencephalopathy Transpl Infect Dis 2000 2 29 32 10.1034/j.1399-3062.2000.020106.x 11429007 \n4. Waggoner J Martinu T Palmer SM Progressive multifocal leukoencephalopathy following heightened immunosuppression after lung transplant J Heart Lung Transplant 2009 28 395 398 10.1016/j.healun.2008.12.010 19332268 \n5. Lobo LJ Reynolds JM Snyder LD Rituximab-associated progressive multifocal leukoencephalopathy after lung transplantation J Heart Lung Transplant 2013 32 752 753 10.1016/j.healun.2013.04.007 23664856 \n6. Moua T Rizza SA Kennedy CC Leg weakness in a lung transplant patient Transpl Infect Dis 2013 15 E102 E106 10.1111/tid.12080 23582024 \n7. Panchabhai TS Choudhary C Isada C Folch E Mehta AC Progressive multifocal leukoencephalopathy in a lung transplant recipient: isolation of John Cunningham (JC) virus from bronchoalveolar lavage J Global Infect Dis 2016 8 51 54 10.4103/0974-777X.176150 \n8. Pavlovic D Patera AC Nyberg F Gerber M Liu M; progressive multifocal Leukeoncephalopathy consortium. Progressive multifocal leukoencephalopathy: current treatment options and future perspectives Ther Adv Neurol Disord 2015 8 255 273 10.1177/1756285615602832 26600871 \n9. Balduzzi A Lucchini G Hirsch HH Basso S Cioni M Rovelli A Polyomavirus JC-targeted T-cell therapy for progressive multiple leukoencephalopathy in a hematopoietic cell transplantation recipient Bone Marrow Transplant 2011 46 987 992 10.1038/bmt.2010.221 20921942 \n10. Wattjes MP Wijburg MT van Eijk J Frequin S Uitdehaag BMJ Barkhof F Dutch-Belgian Natalizumab-associated PML study group. Inflammatory natalizumab-associated PML: baseline characteristics, lesion evolution and relation with PML-IRIS J Neurol Neurosurg Psychiatry 2018 89 535 541 10.1136/jnnp-2017-316886 29142146 \n11. Shah R Bag AK Chapman PR Curé JK Imaging manifestations of progressive multifocal leukoencephalopathy Clin Radiol 2010 65 6 431 439 10.1016/j.crad.2010.03.001 20451009 \n12. Sahraian MA Radue EW Eshaghi A Besliu S Minagar A Progressive multifocal leukoencephalopathy: a review of the neuroimaging features and differential diagnosis Eur J Neurol 2012 19 1060 1069 10.1111/j.1468-1331.2011.03597.x 22136455 \n13. Shitrit D Nirit L Shiran SI Izbicki G Sofer D Eldad M Progressive multifocal leukoencephalopathy in a lung transplant recipient J Heart Lung Transplant 2003 22 946 950 10.1016/S1053-2498(02)00804-5 12909477 \n14. Crowder CD Gyure KA Drachenberg CB Werner J Morales RE Hirsch HH Successful outcome of progressive multifocal leukoencephalopathy in a renal transplant patient Am J Transplant 2005 5 1151 1158 10.1111/j.1600-6143.2005.00800.x 15816900 \n15. Ohara H Kataoka H Nakamichi K Saijo M Ueno S Favorable outcome after withdrawal of immunosuppressant therapy in progressive multifocal leukoencephalopathy after renal transplantation: case report and literature review J Neurol Sci 2014 341 144 146 10.1016/j.jns.2014.03.048 24746292 \n16. Jia JJ Lin BY He JJ Geng L Kadel D Wang L “Minimizing tacrolimus” strategy and long-term survival after liver transplantation World J Gastroenterol 2014 20 11363 11369 10.3748/wjg.v20.i32.11363 25170223 \n17. Dumortier J Guillaud O Bosch A Coppéré B Petiot P Roggerone S Progressive multifocal leukoencephalopathy after liver transplantation can have favorable or unfavorable outcome Transpl Infect Dis 2016 18 606 610 10.1111/tid.12554 27224849 \n18. Sundbom P Hubbert L Serrander L Progressive multifocal leukoencephalopathy after heart transplantation: 4 years of clinically stable infection on low-dose immunosuppressive therapy Oxf Med Case Reports 2017 2017 omx003 10.1093/omcr/omx003 28473916 \n19. Yoshida T Kawamoto M Togo M Kohara N Ito T Nakamichi K Progressive multifocal leukoencephalopathy developing after liver transplantation showing marked neurological symptom improvement and arrest of further deterioration of imaging findings: a case report J Neurol Sci 2015 359 1 3 10.1016/j.jns.2015.10.028 26671076 \n20. Ryschkewitsch CF Jensen PN Monaco MC Major EO JC virus persistence following progressive multifocal leukoencephalopathy in multiple sclerosis patients treated with natalizumab Ann Neurol 2010 68 384 391 10.1002/ana.22137 20818792 \n21. Sospedra M Schippling S Yousef S Jelcic I Bofill-Mas S Planas R Treating progressive multifocal leukoencephalopathy with interleukin 7 and vaccination with JC virus capsid protein VP1 Clin Infect Dis 2014 59 1588 1592 10.1093/cid/ciu682 25214510 \n22. Cortese I Muranski P Enose-Akahata Y Ha SK Smith B Monaco M Pembrolizumab treatment for progressive multifocal Leukoencephalopathy N Engl J Med 2019 380 1597 1605 10.1056/NEJMoa1815039 30969503 \n23. Hoang E Bartlett NL Goyal MS Schmidt RE Clifford DB Progressive multifocal leukoencephalopathy treated with nivolumab J Neuro-Oncol 2019 25 284 287 \n24. Muftuoglu M Olson A Marin D Ahmed S Mulanovich V Tummala S Allogeneic BK virus-specific T cells for progressive multifocal leukoencephalopathy N Engl J Med 2018 379 1443 1451 10.1056/NEJMoa1801540 30304652\n\n", "fulltext_license": "CC BY", "issn_linking": "1471-2377", "issue": "19(1)", "journal": "BMC neurology", "keywords": "CD4 positive cell; Immune reconstitution inflammatory syndrome; JC polyomavirus; Lung transplantation; Mefloquine; Progressive multifocal leukoencephalopathy", "medline_ta": "BMC Neurol", "mesh_terms": "D001921:Brain; D005260:Female; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents; D007577:JC Virus; D007968:Leukoencephalopathy, Progressive Multifocal; D016040:Lung Transplantation; D008875:Middle Aged", "nlm_unique_id": "100968555", "other_id": null, "pages": "263", "pmc": null, "pmid": "31672142", "pubdate": "2019-10-31", "publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review", "references": "30864100;30969503;19332268;29142146;8680884;11429007;26600871;21823157;20451009;28473916;30304652;27013844;25170223;20818792;23664856;24746292;27224849;20921942;22136455;25214510;12909477;23582024;26671076;15816900", "title": "Probable progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation: a case report and literature review.", "title_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review" }

[ { "companynumb": "US-ALKEM LABORATORIES LIMITED-JP-ALKEM-2019-09592", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "2", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "2", "drugadministrationroute": "065", "drugauthorizationnumb": "091249", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": "2", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "CYCLOSPORINE" }, "drugadditional": "2", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOSPORINE." } ], "patientagegroup": null, "patientonsetage": "61", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tracheobronchitis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "JC polyomavirus test positive", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fungal infection", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "3" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, OKADA Y, ET AL.. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW. BMC NEUROLOGY.. 2019?19(1):263", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "US", "receiptdate": "20191227", "receivedate": "20191227", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17205894, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200122" }, { "companynumb": "JP-ALKEM LABORATORIES LIMITED-JP-ALKEM-2019-09591", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "091249", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.5 UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "091249", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ACYCLOVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "MENINGOENCEPHALITIS HERPETIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACYCLOVIR." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ACYCLOVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ENCEPHALOMYELITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACYCLOVIR." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.9 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.9", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Locked-in syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Immune reconstitution inflammatory syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "JC virus infection", "reactionmeddraversionpt": "22.1", "reactionoutcome": "3" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, OKADA Y, ET AL.. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW. BMC NEUROLOGY.. 2019?19(1):263", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20191119", "receivedate": "20191119", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17046697, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200122" }, { "companynumb": "JP-STRIDES ARCOLAB LIMITED-2019SP012040", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK,1.9 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, 500MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DOSE REDUCED TO 0.5 MILLIGRAM IN 5 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK,5MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ACYCLOVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HERPES SIMPLEX", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACICLOVIR" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DOSE REDUCED TO 250 MILLIGRAM IN 5 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Confabulation", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Delusion", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Decreased activity", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Apathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Immune reconstitution inflammatory syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Urinary incontinence", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Locked-in syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperreflexia", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "JC virus infection", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Poverty of speech", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, OKADA Y, NAKAMICHI K, SAIJO M, ET AL. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW. BMC NEUROLOGY. 2019?19(1):263", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20191202", "receivedate": "20191202", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17096857, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": null, "transmissiondate": "20200122" }, { "companynumb": "US-STRIDES ARCOLAB LIMITED-2019SP012392", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, DOSE DECREASED", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, DOSE DECREASED", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "BASILIXIMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BASILIXIMAB" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HUMAN IMMUNOGLOBULIN G" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMMUNOGLOBULIN G HUMAN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CYCLOSPORINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOSPORINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CYCLOSPORINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, DOSE DECREASED", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOSPORINE." } ], "patientagegroup": null, "patientonsetage": "61", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, OKADA Y, NAKAMICHI K, SAIJO M, ET AL. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY?IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW. BMC?NEUROL. 2019?19(1):263", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "US", "receiptdate": "20200730", "receivedate": "20200730", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18094068, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" }, { "companynumb": "JP-MYLANLABS-2019M1116104", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.9 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.9", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL\\MYCOPHENOLATE MOFETIL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CELLCEPT" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Intracranial mass", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "JC virus infection", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Immune reconstitution inflammatory syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Locked-in syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "3" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, OKADA Y, NAKAMICHI K, SAIJO M, ET AL. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW. BMC-NEUROL 2019?19(1):263.. 2019?19(1):263", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20191231", "receivedate": "20191202", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17097828, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200122" }, { "companynumb": "JP-ALKEM LABORATORIES LIMITED-JP-ALKEM-2019-09699", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "091249", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZATHIOPRINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZATHIOPRINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYCLOSPORINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOSPORINE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, OKADA Y, ET AL.. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW. BMC NEUROLOGY.. 2019?19(1):263", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20191119", "receivedate": "20191119", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17046696, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200122" }, { "companynumb": "JP-PBT-000136", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "829160000", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "829160000", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "090802", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.9", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "090802", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS AGAINST TRANSPLANT REJECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." } ], "patientagegroup": "5", "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Medication error", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Urinary incontinence", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "JC virus infection", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Immune reconstitution inflammatory syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, OKADA Y, NAKAMICHI K, SAIJO M. ET AL. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW. BMC NEUROL. 2019 OCT 31?19(1):263. DOI: 10.1186/S12883-019-1493-1.", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20191119", "receivedate": "20191119", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17047769, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200122" }, { "companynumb": "NVSC2019JP037886", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "65379", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "017469", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "65461", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.5 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "017469", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "65379", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "65461", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.9 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "LUNG TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.9", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Apathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, OKADA Y, NAKAMICHI K, SAIJO M ET AL.. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW.. BMC NEUROLOGY. 2019?19:1-7", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20191118", "receivedate": "20191118", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17044710, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200122" }, { "companynumb": "JP-OXFORD PHARMACEUTICALS, LLC-2019OXF00173", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.5 UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "MYCOPHENOLIC ACID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "090606", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "MYCOPHENOLIC ACID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "090606", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.9 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".9", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Immune reconstitution inflammatory syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, ET AL.. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW.. BMC NEUROL.. 2019?19(1)", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20191202", "receivedate": "20191202", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17098450, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200122" }, { "companynumb": "JP-JUBILANT CADISTA PHARMACEUTICALS-2019JUB00441", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.5 UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "090661", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.9 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.9", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "090661", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Immune reconstitution inflammatory syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, ET AL. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW.. BMC NEUROL.. 2019?19(1)", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20191126", "receivedate": "20191126", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17078005, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200122" }, { "companynumb": "JP-ACCORD-160395", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "ACYCLOVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACICLOVIR" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "REDUCED 1.9 TO 0.5 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.9", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MYCOPHENOLIC ACID" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "065416", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "REDUCED 500 TO 250 MG IN 5 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLIC ACID." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, OKADA Y, NAKAMICHI K, SAIJO M. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW. BMC NEUROL. 2019 OCT 31?19(1):263.", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20191118", "receivedate": "20191118", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17042135, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200122" }, { "companynumb": "JP-TEVA-2019-JP-1149512", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "080354", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "65457", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.9 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.9", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Locked-in syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "3" }, { "reactionmeddrapt": "Progressive multifocal leukoencephalopathy", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Immune reconstitution inflammatory syndrome", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Intracranial mass", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "JC virus infection", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "ISHII K, YAMAMOTO F, HOMMA S, OKADA Y, NAKAMICHI K, SAIJO M, ET AL. PROBABLE PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY-IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME WITH IMMUNOSUPPRESSANT DOSE REDUCTION FOLLOWING LUNG TRANSPLANTATION: A CASE REPORT AND LITERATURE REVIEW. BMC-NEUROL 2019?19(1):263.", "literaturereference_normalized": "probable progressive multifocal leukoencephalopathy immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation a case report and literature review", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20191211", "receivedate": "20191211", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17138035, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200122" } ]

{ "abstract": "Acquired haemophilia A (AHA) is a rare and possibly fatal autoimmune disorder that is challenging to treat. Although a majority of cases are idiopathic, AHA can also be associated with an underlying malignancy, autoimmune disorder, pregnancy, infection or certain medications. The diagnosis and treatment of AHA require a specialist with both clinical and laboratory expertise. The goal of treatment is aimed at achieving haemostasis as well as eradicating factor inhibitors. We present a patient with AHA and life-threatening haemorrhage who was successfully treated with a combination of haemostatic agents and a triple-drug immunosuppressive regimen. In reviewing recent studies and published guidelines, we advocate that a newer agent, emicizumab, can potentially be incorporated into the treatment protocol for AHA given its promising performance in the realm of congenital haemophilia.", "affiliations": "Monter Cancer Center, Long Island Jewish Medical Center Northwell Health Cancer Institute, Lake Success, New York, USA.;Monter Cancer Center, Long Island Jewish Medical Center Northwell Health Cancer Institute, Lake Success, New York, USA.;Pathology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA ksticco@northwell.edu.", "authors": "Chung|Su Yun|SY|http://orcid.org/0000-0001-6741-8741;Shen|Janice Gloria|JG|;Sticco|Kristin Lynn|KL|", "chemical_list": "D006490:Hemostatics; D007166:Immunosuppressive Agents", "country": "England", "delete": false, "doi": "10.1136/bcr-2021-242876", "fulltext": null, "fulltext_license": null, "issn_linking": "1757-790X", "issue": "14(6)", "journal": "BMJ case reports", "keywords": "haematology (incl blood transfusion); malignant and benign haematology", "medline_ta": "BMJ Case Rep", "mesh_terms": "D005260:Female; D006467:Hemophilia A; D006470:Hemorrhage; D006490:Hemostatics; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents; D011247:Pregnancy", "nlm_unique_id": "101526291", "other_id": null, "pages": null, "pmc": null, "pmid": "34155028", "pubdate": "2021-06-21", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Acquired haemophilia A: successful treatment of a patient using upfront immunosuppressive therapy and haemostatic agents.", "title_normalized": "acquired haemophilia a successful treatment of a patient using upfront immunosuppressive therapy and haemostatic agents" }

[ { "companynumb": "US-BEH-2021133920", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "ANTIHEMOPHILIC FACTOR, HUMAN RECOMBINANT" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK 3 UNITS", "drugenddate": null, "drugenddateformat": null, "drugindication": "FACTOR VIII DEFICIENCY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FACTOR VIII RECOMBINANT (INN)" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "HUMAN IMMUNOGLOBULIN G" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "125201", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 GRAM PER KILOGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACQUIRED HAEMOPHILIA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HUMAN IMMUNOGLOBULIN (INN)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HUMAN RED BLOOD CELL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "NOT REPORTED", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RED BLOOD CELLS, CONCENTRATED" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HUMAN PLATELET, ALLOGENIC" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "NOT REPORTED", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PLATELETS" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ANTIHEMOPHILIC FACTOR HUMAN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK 3 UNTIS", "drugenddate": null, "drugenddateformat": null, "drugindication": "FACTOR VIII DEFICIENCY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HUMAN FACTOR VIII (INN)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HUMAN PLASMA" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "NOT REPORTED", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK 16 UNITS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FRESH FROZEN PLASMA" } ], "patientagegroup": "6", "patientonsetage": "65", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "No adverse event", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Anti factor VIII antibody increased", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective for unapproved indication", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CHUNG S.Y., SHEN J.G., STICCO K.L.. ACQUIRED HAEMOPHILIA A: SUCCESSFUL TREATMENT OF A PATIENT USING UPFRONT IMMUNOSUPPRESSIVE THERAPY AND HAEMOSTATIC AGENTS. BMJ CASE REPORTS. 2021?14(6)", "literaturereference_normalized": "acquired haemophilia a successful treatment of a patient using upfront immunosuppressive therapy and haemostatic agents", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210726", "receivedate": "20210726", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19612225, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "US-AUROBINDO-AUR-APL-2021-048567", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "210735", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MILLIGRAM/KILOGRAM, ONCE A DAY (FOR 5 DAYS)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Acquired haemophilia", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "COAGULATION FACTOR VIIA RECOMBINANT HUMAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Acquired haemophilia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EPTACOG ALFA" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK (FOR 4 DAYS)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Acquired haemophilia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE" }, { "actiondrug": "5", "activesubstance": null, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 GRAM PER KILOGRAM, ONCE A DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Acquired haemophilia", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMMUNE GLOBULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MILLIGRAM/KILOGRAM, ONCE A DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Acquired haemophilia", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "375 MILLIGRAM/SQ. METER (FOR FOUR DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Acquired haemophilia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "375", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB" } ], "patientagegroup": null, "patientonsetage": "65", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haematoma", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Chung SY, Shen JG, Sticco KL.. Acquired haemophilia A: Successful treatment of a patient using upfront immunosuppressive therapy and haemostatic agents.. BMJ-Case-Rep. 2021;14No.:6", "literaturereference_normalized": "acquired haemophilia a successful treatment of a patient using upfront immunosuppressive therapy and haemostatic agents", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211126", "receivedate": "20211126", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20115503, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" } ]

{ "abstract": "Polyuria in post-kidney transplant (KT) patients is a common condition generally attributed to delayed tubular function, fluid administration, and solute diuresis. Since excessive water intake post-KT physiologically suppresses arginine vasopressin (AVP) secretion, central diabetes insipidus (CDI) caused by deficient primary AVP release can be overlooked. Although DDAVP (desmopressin) - a selective AVP V2 receptor agonist - has been used to treat massive polyuria, CDI rarely progresses to kidney injury due to the preservation of fluid balance by thirst-dependent osmoregulation. Administration of DDAVP in post-KT recipients with mild polyuria and subclinical CDI is difficult to assess, and whether long-term use of DDAVP is beneficial for the transplanted kidney has not been established. We present the case of a 36-year-old Japanese female who was diagnosed with subclinical/partial CDI post KT. CDI was caused by a sequela of suprasellar germinoma. Graft function gradually declined without evidence of hypovolemia or hypernatremia, and a kidney biopsy revealed advanced ischemic kidney injury. Although daily oral DDAVP administration did not increase extracellular fluid volume, treatment resulted in a gradual improvement of graft function, and a follow-up transplanted kidney biopsy indicated substantial recovery.", "affiliations": null, "authors": "Kaneko|Shuzo|S|;Usui|Joichi|J|;Kawanishi|Kunio|K|;Ishii|Ryota|R|;Takahashi|Kazuhiro|K|;Suzuki|Hiroaki|H|;Saito|Chie|C|;Oda|Tatsuya|T|;Nagata|Michio|M|;Yamagata|Kunihiro|K|", "chemical_list": "D003894:Deamino Arginine Vasopressin", "country": "Germany", "delete": false, "doi": "10.5414/CN110295", "fulltext": null, "fulltext_license": null, "issn_linking": "0301-0430", "issue": "95(4)", "journal": "Clinical nephrology", "keywords": null, "medline_ta": "Clin Nephrol", "mesh_terms": "D000284:Administration, Oral; D000328:Adult; D003894:Deamino Arginine Vasopressin; D020790:Diabetes Insipidus, Neurogenic; D005260:Female; D006801:Humans; D007511:Ischemia; D007668:Kidney; D016030:Kidney Transplantation", "nlm_unique_id": "0364441", "other_id": null, "pages": "208-214", "pmc": null, "pmid": "33560220", "pubdate": "2021-04", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Unusual ischemic kidney injury presenting as slowly declining graft function and successful use of oral desmopressin in a kidney transplant recipient with subclinical central diabetes insipidus.", "title_normalized": "unusual ischemic kidney injury presenting as slowly declining graft function and successful use of oral desmopressin in a kidney transplant recipient with subclinical central diabetes insipidus" }

[ { "companynumb": "JP-TEVA-2021-JP-1944535", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVOTHYROXINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPOTHYROIDISM", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVOTHYROXINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "HYDROCORTISONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "087796", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ADRENAL INSUFFICIENCY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCORTISONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GERM CELL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." } ], "patientagegroup": "3", "patientonsetage": "1", "patientonsetageunit": "800", "patientsex": "2", "patientweight": "83", "reaction": [ { "reactionmeddrapt": "Chronic kidney disease", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Diabetes insipidus", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "End stage renal disease", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "KANEKO S, USUI J, KAWANISHI K, ISHII R, TAKAHASHI K, SUZUKI H, ET AL. UNUSUAL ISCHEMIC KIDNEY INJURY PRESENTING AS SLOWLY DECLINING GRAFT FUNCTION AND SUCCESSFUL USE OF ORAL DESMOPRESSIN IN A KIDNEY TRANSPLANT RECIPIENT WITH SUBCLINICAL CENTRAL DIABETES INSIPIDUS. CLIN?NEPHROL 2021?95(4):208?214.", "literaturereference_normalized": "unusual ischemic kidney injury presenting as slowly declining graft function and successful use of oral desmopressin in a kidney transplant recipient with subclinical central diabetes insipidus", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20210825", "receivedate": "20210825", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19744194, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "JP-STRIDES ARCOLAB LIMITED-2021SP026624", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "HYDROCORTISONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "207029", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "ADRENAL INSUFFICIENCY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCORTISONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "GERM CELL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LEVOTHYROXINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPOTHYROIDISM", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVOTHYROXINE." } ], "patientagegroup": null, "patientonsetage": "1", "patientonsetageunit": "800", "patientsex": "2", "patientweight": "83", "reaction": [ { "reactionmeddrapt": "Diabetes insipidus", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "KANEKO S, USUI J, KAWANISHI K, ISHII R, TAKAHASHI K, SUZUKI H, ET AL. UNUSUAL ISCHEMIC KIDNEY INJURY PRESENTING AS SLOWLY DECLINING GRAFT FUNCTION AND SUCCESSFUL USE OF ORAL DESMOPRESSIN IN A KIDNEY TRANSPLANT RECIPIENT WITH SUBCLINICAL CENTRAL DIABETES INSIPIDUS. CLIN?NEPHROL. 2021?95(4):208?214", "literaturereference_normalized": "unusual ischemic kidney injury presenting as slowly declining graft function and successful use of oral desmopressin in a kidney transplant recipient with subclinical central diabetes insipidus", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20210820", "receivedate": "20210820", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19724864, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" } ]

{ "abstract": "OBJECTIVE\nThe optimal management of intraventricular metastases remains debatable. The aim of this study is to define the safety and efficacy of Gamma-Knife radiosurgery in the treatment of intraventricular metastases.\n\n\nMETHODS\nThis retrospective, single-center study involved patients that were treated with stereotactic radiosurgery (SRS) for intraventricular metastases. The study end points included SRS-related toxicity, local and distal intracranial tumor control, as well as the incidence of post-treatment hydrocephalus and leptomeningeal dissemination. Factors associated with radiologic and clinical outcomes were also analyzed.\n\n\nRESULTS\nThe cohort included 17 consecutive patients who underwent stereotactic radiosurgery for treatment of 41 intracranial metastases, of which 23 were primary intraventricular (intraventricular metastasis). Median overall survival from primary tumor diagnosis and from SRS treatment were 28 and 5 months, respectively. With a median radiological follow-up of 3 (interquartile range 3) months, 7 patients (41.18%) experienced overall intracranial disease progression, whereas 7 (27.27%) intraventricular metastases progressed radiologically. Four (23.53%) and 3 (17.65%) patients developed hydrocephalus and leptomeningeal dissemination post-SRS, respectively. Four patients (23.53%) died due to intracranial disease progression.\n\n\nCONCLUSIONS\nSRS offers a reasonable chance of local tumor control for patients with intraventricular brain metastasis. However, the risk of hydrocephalus and leptomeningeal spread of disease is not inconsequential and merits close follow-up for patients with brain metastasis involving the ventricular system.", "affiliations": "Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA.;Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA.;Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA.;Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia, USA. Electronic address: jsheehan@virginia.edu.", "authors": "Mantziaris|Georgios|G|;Pikis|Stylianos|S|;Marquis|Olivia|O|;Sheehan|Jason|J|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1016/j.wneu.2021.10.083", "fulltext": null, "fulltext_license": null, "issn_linking": "1878-8750", "issue": null, "journal": "World neurosurgery", "keywords": "Brain metastases; Hydrocephalus; Intraventricular; Leptomeningeal dissemination; Stereotactic radiosurgery", "medline_ta": "World Neurosurg", "mesh_terms": null, "nlm_unique_id": "101528275", "other_id": null, "pages": null, "pmc": null, "pmid": "34653703", "pubdate": "2021-10-12", "publication_types": "D016428:Journal Article", "references": null, "title": "Radiologic and Clinical Outcomes of Stereotactic Radiosurgery for Intraventricular Metastases.", "title_normalized": "radiologic and clinical outcomes of stereotactic radiosurgery for intraventricular metastases" }

[ { "companynumb": "US-AMGEN-USASP2022058231", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BEVACIZUMAB" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "761028", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Unknown formulation", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Metastases to central nervous system", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BEVACIZUMAB" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "BEVACIZUMAB" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "761028", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Unknown formulation", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Off label use", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BEVACIZUMAB" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Metastases to central nervous system", "reactionmeddraversionpt": "25.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Device malfunction", "reactionmeddraversionpt": "25.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Hydrocephalus", "reactionmeddraversionpt": "25.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Brain oedema", "reactionmeddraversionpt": "25.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Sheehan J.; Mantziaris G.; Pikis S. et al.. Radiologic and Clinical Outcomes of Stereotactic Radiosurgery for Intraventricular Metastases. World Neurosurgery. 2022;157:e333-e341", "literaturereference_normalized": "radiologic and clinical outcomes of stereotactic radiosurgery for intraventricular metastases", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20220408", "receivedate": "20220408", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20687938, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" } ]

{ "abstract": "We present a case of malignant pleural mesothelioma which responded to a cisplatin plus pemetrexed rechallenge. A 78- year-old man was diagnosed as stage IV malignant pleural mesothelioma in International Mesothelioma Interest Group (IMIG) stage by biopsy using ultrasonography and chest to abdominal CT. 6 courses of cisplatin at 60 mg/m2 plus pemetrexed at 500 mg/m2 were administered every 3 to 4 weeks. After this treatment, all of the lesions shrank, and the best overall response was partial response (PR) in Response Evaluation Criteria in Solid Tumors (RECIST). Although vinorelbine, gemcitabine and S-1 were administered subsequently because of the re-growth of the lesions, they were enlarged. Cisplatin plus pemetrexed was administered as fifth-line chemotherapy again, the lesions shrank, and the best overall response was PR in RECIST.", "affiliations": "Division of Thoracic Oncology, Shizuoka Cancer Center.", "authors": "Shukuya|Takehito|T|;Takahashi|Toshiaki|T|;Nakamura|Yukiko|Y|;Yamamoto|Nobuyuki|N|", "chemical_list": "D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin", "country": "Japan", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0385-0684", "issue": "37(3)", "journal": "Gan to kagaku ryoho. Cancer & chemotherapy", "keywords": null, "medline_ta": "Gan To Kagaku Ryoho", "mesh_terms": "D000368:Aged; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000971:Antineoplastic Combined Chemotherapy Protocols; D002945:Cisplatin; D005971:Glutamates; D006147:Guanine; D006801:Humans; D008297:Male; D008654:Mesothelioma; D000068437:Pemetrexed; D010997:Pleural Neoplasms", "nlm_unique_id": "7810034", "other_id": null, "pages": "487-90", "pmc": null, "pmid": "20332689", "pubdate": "2010-03", "publication_types": "D002363:Case Reports; D004740:English Abstract; D016428:Journal Article", "references": null, "title": "A case of malignant pleural mesothelioma that responded to cisplatin plus pemetrexed rechallenge.", "title_normalized": "a case of malignant pleural mesothelioma that responded to cisplatin plus pemetrexed rechallenge" }

[ { "companynumb": "JP-SUN PHARMACEUTICAL INDUSTRIES LTD-2016RR-115086", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "6 COURSES OF 60 MG/M2 EVERY 3 TO 4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20070315", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PEMETREXED" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG/M2 EVERY 3 TO 4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20070315", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEMETREXED" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "GIMERACIL\\OTERACIL\\TEGAFUR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20071107", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TS-1" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "GEMCITABINE\\GEMCITABINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78433", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG/M2, ON DAY 1, 8, 15, EVERY 4 WEEKS (2 COURSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080417", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080825", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINORELBINE\\VINORELBINE TARTRATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG/M2 IN DAY 1, 8, 15, EVERY 4 WEEKS (2 COURSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080221", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINORELBINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYANOCOBALAMIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.0MG/ 9 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VITAMIN B12" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "45 MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FOLIC ACID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.5 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FOLIC ACID." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PEMETREXED" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080825", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEMETREXED" } ], "patientagegroup": null, "patientonsetage": "78", "patientonsetageunit": "801", "patientsex": "1", "patientweight": "62.7", "reaction": [ { "reactionmeddrapt": "Drug effect decreased", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Disease progression", "reactionmeddraversionpt": "19.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Oral disorder", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Blood creatinine increased", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Decreased appetite", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Leukopenia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hiccups", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Platelet count decreased", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Enteritis", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SHUKUYA T, TAKAHASHI T, NAKAMURA Y, YAMAMOTO N. A CASE OF MALIGNANT PLEURAL MESOTHELIOMA THAT RESPONDED TO CISPLATIN PLUS PEMETREXED RECHALLENGE. GAN-TO-KAGAKU-RYOHO. 2010;37 (3):487-490", "literaturereference_normalized": "a case of malignant pleural mesothelioma that responded to cisplatin plus pemetrexed rechallenge", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20160518", "receivedate": "20160518", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12381276, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20160815" }, { "companynumb": "JP-TEVA-652597ISR", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PEMETREXED" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG/M2 ON DAY1 REPEATED AT EVERY 3-4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20070315", "drugstartdateformat": "102", "drugstructuredosagenumb": "500", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEMETREXED" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "GEMCITABINE\\GEMCITABINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG/M2 ON DAY 1, 8 AND DAY15; REPEATED EVERY 4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080417", "drugstartdateformat": "102", "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "74656", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2 ON DAY1 REPEATED AT EVERY 3-4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20070315", "drugstartdateformat": "102", "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PEMETREXED" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080825", "drugstartdateformat": "102", "drugstructuredosagenumb": "500", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEMETREXED" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "GIMERACIL\\OTERACIL\\TEGAFUR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080711", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GIMERACIL, OTERACIL, TEGAFUR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "74656", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080825", "drugstartdateformat": "102", "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "VINORELBINE\\VINORELBINE TARTRATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG/M2 ON DAY 1, 8 AND DAY15; REPEATED EVERY 4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080221", "drugstartdateformat": "102", "drugstructuredosagenumb": "25", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINORELBINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "74656", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "45", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FOLIC ACID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FOLIC ACID." } ], "patientagegroup": null, "patientonsetage": "78", "patientonsetageunit": "801", "patientsex": "1", "patientweight": "62.7", "reaction": [ { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Decreased appetite", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Leukopenia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Thrombocytopenia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Enteritis", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hiccups", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SHUKUYA T, TAKAHASHI T, NAKAMURA Y, YAMAMOTO N. A CASE OF MALIGNANT PLEURAL MESOTHELIOMA THAT RESPONDED TO CISPLATIN PLUS PEMETREXED RECHALLENGE. [JAPANESE]. GAN-TO-KAGAKU-RYOHO 2010;37(3):487-490.", "literaturereference_normalized": "a case of malignant pleural mesothelioma that responded to cisplatin plus pemetrexed rechallenge", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20160422", "receivedate": "20160422", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12296351, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20160815" }, { "companynumb": "JP-MYLANLABS-2016M1015199", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PEMETREXED" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG/M2 ON DAY1 REPEATED AT EVERY 3-4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20070315", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEMETREXED" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "091062", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080825", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "GIMERACIL\\OTERACIL\\TEGAFUR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080711", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GIMERACIL W/OTERACIL POTASSIUM/TEGAFUR" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "FOLIC ACID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.5MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FOLIC ACID." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "091062", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2 ON DAY1 REPEATED AT EVERY 3-4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20070315", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PEMETREXED" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080825", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEMETREXED" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "VINORELBINE\\VINORELBINE TARTRATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG/M2 ON DAY 1, 8 AND DAY15; REPEATED EVERY 4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080221", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINORELBINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "091062", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "45 MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GEMCITABINE\\GEMCITABINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG/M2 ON DAY 1, 8 AND DAY15; REPEATED EVERY 4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLEURAL MESOTHELIOMA MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20080417", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hiccups", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Enteritis", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Leukopenia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Thrombocytopenia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Decreased appetite", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SHUKUYA T, TAKAHASHI T, NAKAMURA Y, YAMAMOTO N. A CASE OF MALIGNANT PLEURAL MESOTHELIOMA THAT RESPONDED TO CISPLATIN PLUS PEMETREXED RECHALLENGE. [JAPANESE]. GAN-TO-KAGAKU-RYOHO 2010;37(3):487-490.", "literaturereference_normalized": "a case of malignant pleural mesothelioma that responded to cisplatin plus pemetrexed rechallenge", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20160414", "receivedate": "20160414", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12267773, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20160815" } ]

{ "abstract": "Coronavirus disease 2019 (COVID-19) has become a pandemic since first being described in January 2020. Clinical manifestations in non-transplant patients range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome, multiorgan system failure, and death. Limited reports in kidney transplant recipients suggest similar characteristics in that population. We report here the first case series of COVID-19 infection occurring in pancreas transplant recipients.", "affiliations": "Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.;Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.;Department of Surgery, Columbia University Irving Medical Center, New York, New York, USA.;Department of Surgery, Columbia University Irving Medical Center, New York, New York, USA.;Department of Surgery, Columbia University Irving Medical Center, New York, New York, USA.;Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.", "authors": "Dube|Geoffrey K|GK|https://orcid.org/0000-0003-0206-5652;Husain|S Ali|SA|https://orcid.org/0000-0002-1823-0117;McCune|Kasi R|KR|https://orcid.org/0000-0001-6482-8665;Sandoval|P Rodrigo|PR|https://orcid.org/0000-0003-4833-3974;Ratner|Lloyd E|LE|https://orcid.org/0000-0002-1564-9617;Cohen|David J|DJ|https://orcid.org/0000-0003-1227-3252", "chemical_list": "D007166:Immunosuppressive Agents", "country": "Denmark", "delete": false, "doi": "10.1111/tid.13359", "fulltext": null, "fulltext_license": null, "issn_linking": "1398-2273", "issue": "22(6)", "journal": "Transplant infectious disease : an official journal of the Transplantation Society", "keywords": "COVID-19; SARS-CoV-2; coronavirus; pancreas transplant", "medline_ta": "Transpl Infect Dis", "mesh_terms": "D000328:Adult; D000553:Ambulatory Care; D000086382:COVID-19; D000069340:Deprescriptions; D003922:Diabetes Mellitus, Type 1; D003928:Diabetic Nephropathies; D005260:Female; D006084:Graft Rejection; D006760:Hospitalization; D006801:Humans; D007166:Immunosuppressive Agents; D007676:Kidney Failure, Chronic; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D012131:Respiratory Insufficiency; D000086402:SARS-CoV-2; D017216:Telemedicine", "nlm_unique_id": "100883688", "other_id": null, "pages": "e13359", "pmc": null, "pmid": "32515076", "pubdate": "2020-12", "publication_types": "D016428:Journal Article", "references": null, "title": "COVID-19 in pancreas transplant recipients.", "title_normalized": "covid 19 in pancreas transplant recipients" }

[ { "companynumb": "US-STRIDES ARCOLAB LIMITED-2021SP001757", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THYMOGLOBULIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "90687", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "90687", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, MAINTENANCE IMMUNOSUPPRESSION", "drugenddate": "2020", "drugenddateformat": "602", "drugindication": "PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, INDUCTION IMMUNOSUPPRESSANT THERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THYMOGLOBULIN" } ], "patientagegroup": null, "patientonsetage": "53", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2020" } }, "primarysource": { "literaturereference": "DUBE GK, HUSAIN SA, MCCUNE KR, SANDOVAL PR, RATNER LE, COHEN DJ.. COVID?19 IN PANCREAS TRANSPLANT RECIPIENTS.. TRANSPL?INFECT?DIS. 2020?22(6):E13359", "literaturereference_normalized": "covid 19 in pancreas transplant recipients", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210915", "receivedate": "20210915", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19833577, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "US-STRIDES ARCOLAB LIMITED-2021SP001760", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN" } ], "patientagegroup": null, "patientonsetage": "36", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "DUBE GK, HUSAIN SA, MCCUNE KR, SANDOVAL PR, RATNER LE, COHEN DJ.. COVID?19 IN PANCREAS TRANSPLANT RECIPIENTS. TRANSPL?INFECT?DIS. 2020?22(6):E13359", "literaturereference_normalized": "covid 19 in pancreas transplant recipients", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210802", "receivedate": "20210802", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19644678, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" }, { "companynumb": "US-MYLANLABS-2021M1007776", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROXYCHLOROQUINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THYMOGLOBULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZITHROMYCIN ANHYDROUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZITHROMYCIN ANHYDROUS." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "065520", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "2020", "drugenddateformat": "602", "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." } ], "patientagegroup": null, "patientonsetage": "36", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2020" } }, "primarysource": { "literaturereference": "DUBE GK, HUSAIN SA, MCCUNE KR, SANDOVAL PR, RATNER LE, COHEN DJ. COVID?19 IN PANCREAS TRANSPLANT RECIPIENTS. TRANSPL?INFECT?DIS 2020?22(6):E13359.", "literaturereference_normalized": "covid 19 in pancreas transplant recipients", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210209", "receivedate": "20210209", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18867706, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210420" }, { "companynumb": "US-TEVA-2021-US-1879737", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "40081", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROXYCHLOROQUINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZITHROMYCIN ANHYDROUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "65150", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZITHROMYCIN ANHYDROUS." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLIC ACID" }, "drugadditional": "2", "drugadministrationroute": "065", "drugauthorizationnumb": "65457", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": "2020", "drugenddateformat": "602", "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THYMOGLOBULIN" } ], "patientagegroup": "5", "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "3" }, { "reactionmeddrapt": "Respiratory arrest", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2020" } }, "primarysource": { "literaturereference": "DUBE GK, HUSAIN SA, MCCUNE KR, SANDOVAL PR, RATNER LE, COHEN DJ. COVID?19 IN PANCREAS TRANSPLANT RECIPIENTS. TRANSPL?INFECT?DIS 2020?22(6):E13359.", "literaturereference_normalized": "covid 19 in pancreas transplant recipients", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210216", "receivedate": "20210216", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18900509, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210420" }, { "companynumb": "US-TEVA-2021-US-1879736", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "40081", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROXYCHLOROQUINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "65457", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": "2020", "drugenddateformat": "602", "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THYMOGLOBULIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZITHROMYCIN ANHYDROUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "65150", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZITHROMYCIN ANHYDROUS." } ], "patientagegroup": "5", "patientonsetage": "36", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2020" } }, "primarysource": { "literaturereference": "DUBE GK, HUSAIN SA, MCCUNE KR, SANDOVAL PR, RATNER LE, COHEN DJ. COVID?19 IN PANCREAS TRANSPLANT RECIPIENTS. TRANSPL?INFECT?DIS 2020?22(6):E13359.", "literaturereference_normalized": "covid 19 in pancreas transplant recipients", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210727", "receivedate": "20210216", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18902149, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" }, { "companynumb": "US-MYLANLABS-2021M1007774", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THYMOGLOBULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "090596", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZITHROMYCIN ANHYDROUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZITHROMYCIN ANHYDROUS." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "2020", "drugenddateformat": "602", "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROXYCHLOROQUINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Respiratory arrest", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2020" } }, "primarysource": { "literaturereference": "DUBE GK, HUSAIN SA, MCCUNE KR, SANDOVAL PR, RATNER LE, COHEN DJ. COVID?19 IN PANCREAS TRANSPLANT RECIPIENTS. TRANSPL?INFECT?DIS 2020?22(6):E13359.", "literaturereference_normalized": "covid 19 in pancreas transplant recipients", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210209", "receivedate": "20210209", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18867669, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210420" }, { "companynumb": "NVSC2020US179904", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "65379", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "65379", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "65461", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "65461", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Anosmia", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Dyspnoea", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Cough", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Headache", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "23.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "DUBE GK, HUSAIN SA, MCCUNE KR, SANDOVA PR, RATNER LE, COHEN DL.. COVID-19 IN PANCREAS TRANSPLANT RECIPIENTS. TRANSPLANT INFECTIOUS DISEASE. 2020", "literaturereference_normalized": "covid 19 in pancreas transplant recipients", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200626", "receivedate": "20200626", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17952532, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200714" }, { "companynumb": "US-STRIDES ARCOLAB LIMITED-2021SP001758", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL AND PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL AND PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL AND PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THYMOGLOBULIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, RESUMED", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." } ], "patientagegroup": null, "patientonsetage": "40", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "DUBE GK, HUSAIN SA, MCCUNE KR, SANDOVAL PR, RATNER LE, COHEN DJ.. COVID?19 IN PANCREAS TRANSPLANT RECIPIENTS. TRANSPL?INFECT?DIS. 2020?22(6):E13359", "literaturereference_normalized": "covid 19 in pancreas transplant recipients", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210802", "receivedate": "20210802", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19644682, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "US-HIKMA PHARMACEUTICALS USA INC.-US-H14001-21-00852", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLIC ACID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "065410", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "DUBE G, HUSAIN S, MCCUNE K, SANDOVAL P, RATNER L, COHEN D. COVID?19 IN PANCREAS TRANSPLANT RECIPIENTS. TRANSPLANT INFECTIOUS DISEASE. 2020?22:6:. DOI:10.1111/TID.13359", "literaturereference_normalized": "covid 19 in pancreas transplant recipients", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20210224", "receivedate": "20210224", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18933251, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "US-STRIDES ARCOLAB LIMITED-2021SP001759", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "90055", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THYMOGLOBULIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK (INDUCTION)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREAS TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THYMOGLOBULIN" } ], "patientagegroup": null, "patientonsetage": "60", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "DUBE GK, HUSAIN SA, MCCUNE KR, SANDOVAL PR, RATNER LE, COHEN DJ.. COVID?19 IN PANCREAS TRANSPLANT RECIPIENTS.. TRANSPL?INFECT?DIS. 2020?22(6):E13359", "literaturereference_normalized": "covid 19 in pancreas transplant recipients", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210211", "receivedate": "20210211", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18879243, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210420" } ]

{ "abstract": "Anticonvulsants are considered a second line option for bipolar disorder, it is known that the abrupt withdrawal is rarely related with demyelinated lesions of the splenium of the corpus callosum. Oxcarbazepine is used in bipolar disorder although it is not stated in the data sheet.\n\n\n\nWe presented a case of a 50 years old woman with bipolar disorder who is treated with lithium and oxcarbazepine, she presented a manic episode and a confusional syndrome after she stopped taking the medication. The magnetic resonance showed a restricted diffusion area at the splenium of the corpus callosum and bifrontal hygromas that disappear two weeks later.\n\n\n\nThe results of this study suggest that for a patient presenting with a mild encephalopathy and reversible splenial lesion, one should consider whether it is related to withdrawal of oxcarbazepine.", "affiliations": "\"La Fe\" Hospital, Valencia, Spain. Electronic address: mmerizaldet@hotmail.com.;\"La Fe\" Hospital, Valencia, Spain.;\"La Fe\" Hospital, Valencia, Spain.;\"La Fe\" Hospital, Valencia, Spain.;\"La Fe\" Hospital, Valencia, Spain.;\"La Fe\" Hospital, Valencia, Spain.", "authors": "Merizalde|Milton|M|;Navalón|Pablo|P|;González|María Fernanda|MF|;Domínguez|Alberto|A|;Livianos|Lorenzo|L|;Martínez|Juan Carlos|JC|", "chemical_list": "D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine", "country": "Netherlands", "delete": false, "doi": "10.1016/j.jad.2016.12.018", "fulltext": null, "fulltext_license": null, "issn_linking": "0165-0327", "issue": "210()", "journal": "Journal of affective disorders", "keywords": "Bipolar disease; Encephalopathy; Manic episode; Oxcarbazepine", "medline_ta": "J Affect Disord", "mesh_terms": "D000927:Anticonvulsants; D001714:Bipolar Disorder; D002220:Carbamazepine; D003221:Confusion; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D000078330:Oxcarbazepine; D013158:Splenic Diseases; D013375:Substance Withdrawal Syndrome", "nlm_unique_id": "7906073", "other_id": null, "pages": "122-124", "pmc": null, "pmid": "28027511", "pubdate": "2017-03-01", "publication_types": "D002363:Case Reports; D016422:Letter", "references": null, "title": "Manic espisode, confusional syndrome and reversible splenial lesion after abrupt withdrawal of oxcarbazepine.", "title_normalized": "manic espisode confusional syndrome and reversible splenial lesion after abrupt withdrawal of oxcarbazepine" }

[ { "companynumb": "PHHY2016ES180949", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LITHIUM" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "800 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "800", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LITHIUM." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "OXCARBAZEPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "021014", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1200 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "20131025", "drugstartdateformat": "102", "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXCARBAZEPINE." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Confusional state", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Mania", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug withdrawal syndrome", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Central nervous system lesion", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Encephalopathy", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MERIZALDE M, NAVALON P, GONZALEZ MF, DOMINGUEZ A, LIVIANOS L, MARTINEZ JC. MANIC ESPISODE, CONFUSIONAL SYNDROME AND REVERSIBLE SPLENIAL LESION AFTER ABRUPT WITHDRAWAL OF OXCARBAZEPINE. JOURNAL OF AFFECTIVE DISORDERS. 2017;210:122-4", "literaturereference_normalized": "manic espisode confusional syndrome and reversible splenial lesion after abrupt withdrawal of oxcarbazepine", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20170127", "receivedate": "20170104", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13086124, "safetyreportversion": 4, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20170428" }, { "companynumb": "ES-ALEMBIC PHARMACUETICALS LIMITED-2017SCAL000022", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "LITHIUM CARBONATE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "079159", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "800 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "800", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LITHIUM CARBONATE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "OXCARBAZEPINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1200 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXCARBAZEPINE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Central nervous system lesion", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Mania", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Psychomotor hyperactivity", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Euphoric mood", "reactionmeddraversionpt": "19.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Drug withdrawal syndrome", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Confusional state", "reactionmeddraversionpt": "19.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Insomnia", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Verbigeration", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MERIZALDE M, NAVALON P, GONZALEZ M F, DOMINGUEZ A, LIVIANOS L, MARTINEZ J C. MANIC ESPISODE, CONFUSIONAL SYNDROME AND REVERSIBLE SPLENIAL LESION AFTER ABRUPT WITHDRAWAL OF OXCARBAZEPINE. JOURNAL OF AFFECTIVE DISORDERS. 2017;210:122-124", "literaturereference_normalized": "manic espisode confusional syndrome and reversible splenial lesion after abrupt withdrawal of oxcarbazepine", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20170112", "receivedate": "20170112", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13107146, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20170428" }, { "companynumb": "ES-GLENMARK PHARMACEUTICALS-2017GMK025930", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXCARBAZEPINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "077802", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1200 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20131025", "drugstartdateformat": "102", "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXCARBAZEPINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LITHIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LITHIUM." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug withdrawal syndrome", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Encephalopathy", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Confusional state", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Central nervous system lesion", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Mania", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MERIZALDE M, NAVALON P, GONZALEZ MF, DOMINGUEZ A,LIVIANOS L, MARTINEZ JC.. MANIC ESPISODE, CONFUSIONAL SYNDROME AND REVERSIBLE SPLENIAL LESION AFTER ABRUPT WITHDRAWAL OF OXCARBAZEPINE. JOURNAL OF AFFECTIVE DISORDERS. 2017;210:122-124", "literaturereference_normalized": "manic espisode confusional syndrome and reversible splenial lesion after abrupt withdrawal of oxcarbazepine", "qualification": "1", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20170131", "receivedate": "20170123", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13137516, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20170428" }, { "companynumb": "ES-SUPERNUS PHARMACEUTICALS, INC.-2017SUP00019", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "LITHIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "800 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "800", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LITHIUM." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "OXCARBAZEPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "202810", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1200 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXCARBAZEPINE." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Central nervous system lesion", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Encephalopathy", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Withdrawal syndrome", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "MERIZALDE M, NAVALON P, GONZALEZ MF, DOMINGUEZ A, LIVIANOS L, MARTINEZ JC. MANIC ESPISODE, CONFUSIONAL SYNDROME AND REVERSIBLE SPLENIAL LESION AFTER ABRUPT WITHDRAWAL OF OXCARBAZEPINE. J AFFECTIVE DISORD (DOI: 10.1016/J.JAD.2016.12.018). 2017;210:122-124", "literaturereference_normalized": "manic espisode confusional syndrome and reversible splenial lesion after abrupt withdrawal of oxcarbazepine", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20170207", "receivedate": "20170207", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13193226, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20170428" }, { "companynumb": "ES-JUBILANT CADISTA PHARMACEUTICALS-2017JUB00033", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "OXCARBAZEPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "090239", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1200 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXCARBAZEPINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LITHIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "800 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "BIPOLAR DISORDER", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "800", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LITHIUM." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Central nervous system lesion", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Withdrawal syndrome", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Encephalopathy", "reactionmeddraversionpt": "19.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "MERIZALDE M, NAVALON P, GONZALEZ MF, DOMINGUEZ A, LIVIANOS L, MARTINEZ JC. MANIC ESPISODE, CONFUSIONAL SYNDROME AND REVERSIBLE SPLENIAL LESION AFTER ABRUPT WITHDRAWAL OF OXCARBAZEPINE. J AFFECTIVE DISORD (DOI: 10.1016/J.JAD.2016.12.018). 2017;210:122-124", "literaturereference_normalized": "manic espisode confusional syndrome and reversible splenial lesion after abrupt withdrawal of oxcarbazepine", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20170203", "receivedate": "20170203", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13185702, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20170428" } ]

{ "abstract": "Neurological side-effects of linezolid manifesting as a posterior reversible leuco-encephalopathy syndrome (PRES) is rare. Early identification of this offending drug might reverse this catastrophic event. We report a 45-year-old female, who was diagnosed as a case of disseminated tuberculosis and was treated with antitubercular drugs (ATT), but later developed ATT-induced hepatitis. She was then put on modified ATT (moxifloxacin, terizidone, and linezolid). In the next two days she developed an altered sensorium. Brain imaging was suggestive of PRES. Linezolid was withdrawn, following which she showed an excellent clinical and radiological recovery.", "affiliations": "Department of Radiology, 28928Sir Ganga Ram Hospital, Old Rajendra Nagar, New Delhi, India.;Department of Radiology, 28928Sir Ganga Ram Hospital, Old Rajendra Nagar, New Delhi, India.;Department of Radiology, 28928Sir Ganga Ram Hospital, Old Rajendra Nagar, New Delhi, India.;Department of Radiology, 28928Sir Ganga Ram Hospital, Old Rajendra Nagar, New Delhi, India.", "authors": "Tomar|Laxmikant Ramkumarsingh|LR|https://orcid.org/0000-0001-6019-655X;Pandita|Neha|N|;Arya|Sakshi|S|;Agrawal|C S|CS|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1177/00494755211053194", "fulltext": null, "fulltext_license": null, "issn_linking": "0049-4755", "issue": null, "journal": "Tropical doctor", "keywords": "PRES; Tuberculosis; linezolid; magnetic resonance imaging", "medline_ta": "Trop Doct", "mesh_terms": null, "nlm_unique_id": "1301706", "other_id": null, "pages": "494755211053194", "pmc": null, "pmid": "34866511", "pubdate": "2021-12-06", "publication_types": "D016428:Journal Article", "references": null, "title": "Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis.", "title_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis" }

[ { "companynumb": "IN-HQ-000161", "fulfillexpeditecriteria": "1", "occurcountry": null, "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Tablet", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMIKACIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMIKACIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MOXIFLOXACIN" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOXIFLOXACIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "TERIZIDONE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TERIZIDONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE" } ], "patientagegroup": null, "patientonsetage": "45", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Tomar LR, Pandita N, Arya S, Agrawal CS. Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis. Trop Doct. 2021 Dec 6:494755211053194. doi: 10.1177/00494755211053194.", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "1", "reportercountry": "IN" }, "primarysourcecountry": "IN", "receiptdate": "20211220", "receivedate": "20211220", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20208424, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220304" }, { "companynumb": null, "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "200904", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1200 MG, QD (SOLUTION, STERILE)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TORSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TORSEMIDE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ALLOPURINOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "300 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALLOPURINOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METAMIZOLE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METAMIZOLE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "90 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "90", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "HYDROCHLOROTHIAZIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCHLOROTHIAZIDE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OMEPRAZOLE MAGNESIUM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMEPRAZOLE MAGNESIUM" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NADROPARIN CALCIUM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5700 IU", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5700", "drugstructuredosageunit": "025", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NADROPARIN CALCIUM" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IODINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IODINE" } ], "patientagegroup": null, "patientonsetage": "71", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Partial seizures", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Visual impairment", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20050724" } }, "primarysource": { "literaturereference": "Tomar LR. Linezolid-associated posterior reversible leuco-encephalopathy syndrome in a patient with disseminated tuberculosis. TROPICAL DOCTOR. 2021;1-3", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20220616", "receivedate": "20220616", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20968507, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220720" }, { "companynumb": "IN-LUPIN PHARMACEUTICALS INC.-2021-26510", "fulfillexpeditecriteria": "1", "occurcountry": "IN", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "207526", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "090034", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PYRAZINAMIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Tablet", "drugdosagetext": "1.5 GRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRAZINAMIDE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "078939", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Tablet", "drugdosagetext": "1 GRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL HYDROCHLORIDE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ISONIAZID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Tablet", "drugdosagetext": "300 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ISONIAZID" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "AMIKACIN" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 GRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMIKACIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MOXIFLOXACIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOXIFLOXACIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TERIZIDONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MILLIGRAM, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TERIZIDONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MILLIGRAM, THRICE A DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE" } ], "patientagegroup": null, "patientonsetage": "45", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hepatitis", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Tomar LR, Pandita N, Arya S, Agrawal CS. Linezolid-associated posterior reversible leuco-encephalopathy syndrome in a patient with disseminated tuberculosis. Tropical doctor. 2021;1-3", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "1", "reportercountry": "IN" }, "primarysourcecountry": "IN", "receiptdate": "20220111", "receivedate": "20220111", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20320438, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220424" }, { "companynumb": "IN-AMNEAL PHARMACEUTICALS-2021-AMRX-05094", "fulfillexpeditecriteria": "1", "occurcountry": "IN", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "204536", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Drug-induced liver injury", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MOXIFLOXACIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Drug-induced liver injury", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOXIFLOXACIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TERIZIDONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Drug-induced liver injury", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TERIZIDONE" } ], "patientagegroup": null, "patientonsetage": "45", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Tomar LR, Pandita N, Arya S, Agrawal CS. Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis. Trop. Doct.. 2021", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "3", "reportercountry": "IN" }, "primarysourcecountry": "IN", "receiptdate": "20211227", "receivedate": "20211227", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20232609, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "DE-ALKEM LABORATORIES LIMITED-DE-ALKEM-2021-08533", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "206917", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1200 MILLIGRAM, ONCE A DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ALLOPURINOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "300 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALLOPURINOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "HYDROCHLOROTHIAZIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCHLOROTHIAZIDE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IODINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IODINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METAMIZOLE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METAMIZOLE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "90 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "90", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NADROPARIN CALCIUM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5700 INTERNATIONAL UNIT", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5700", "drugstructuredosageunit": "025", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NADROPARIN CALCIUM" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OMEPRAZOLE MAGNESIUM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMEPRAZOLE MAGNESIUM" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM, ONCE A DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TORSEMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TORSEMIDE" } ], "patientagegroup": null, "patientonsetage": "71", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Visual impairment", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Partial seizures", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20050724" } }, "primarysource": { "literaturereference": "Laxmikant Ramkumarsingh Tomar. Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis.. Tropical Doctor.. 2021;1-3", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20220623", "receivedate": "20220121", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20359999, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" }, { "companynumb": "CLT-IN-2022-0417-236423", "fulfillexpeditecriteria": "1", "occurcountry": "IN", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "210702", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MOXIFLOXACIN" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOXIFLOXACIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "TERIZIDONE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TERIZIDONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMIKACIN" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMIKACIN" } ], "patientagegroup": null, "patientonsetage": "45", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Tomar LR, Pandita N, Arya S, Agrawal CS. Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis. Trop Doct. 2022 Jan; 52(1):196-198", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "3", "reportercountry": "IN" }, "primarysourcecountry": "IN", "receiptdate": "20220321", "receivedate": "20220321", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20616962, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" }, { "companynumb": "IN-HETERO-HET2021IN02304", "fulfillexpeditecriteria": "1", "occurcountry": "IN", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 G, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AMIKACIN" }, "drugadditional": "4", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "1 G, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMIKACIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MOXIFLOXACIN" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOXIFLOXACIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "TERIZIDONE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MG, T.D.S.", "drugenddate": null, "drugenddateformat": null, "drugindication": "Tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TERIZIDONE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, T.D.S.", "drugenddate": null, "drugenddateformat": null, "drugindication": "Tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE" } ], "patientagegroup": null, "patientonsetage": "45", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Tomar LR, Pandita N, Arya S, Agrawal CS.. Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis. Tropical Doctor. 2021;0(0):1-3", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "1", "reportercountry": "IN" }, "primarysourcecountry": "IN", "receiptdate": "20211222", "receivedate": "20211222", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20215542, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "DE-ALKEM LABORATORIES LIMITED-DE-ALKEM-2021-08533", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "205154", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1200 MILLIGRAM, QD (DAILY DOSE: 1200 MG MILLIGRAM(S) EVERY DAY, SOLUTION, STERILE)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TORSEMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TORSEMIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "RAMIPRIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMIPRIL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM, QD (DAILY DOSE: 600 MG MILLIGRAM(S) EVERY DAY)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ALLOPURINOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "300 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALLOPURINOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METAMIZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METAMIZOLE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "90 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "90", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HYDROCHLOROTHIAZIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCHLOROTHIAZIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "OMEPRAZOLE MAGNESIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMEPRAZOLE MAGNESIUM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NADROPARIN CALCIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5700 INTERNATIONAL UNIT", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5700", "drugstructuredosageunit": "025", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NADROPARIN CALCIUM" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IODINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IODINE" } ], "patientagegroup": null, "patientonsetage": "71", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Visual impairment", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Partial seizures", "reactionmeddraversionpt": "25.0", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20050724" } }, "primarysource": { "literaturereference": "Laxmikant Ramkumarsingh T.. Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis. Tropical Doctor. 2021;Unk:1?3", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20220622", "receivedate": "20220126", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20378590, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" }, { "companynumb": "IN-BAYER-2021A272761", "fulfillexpeditecriteria": "1", "occurcountry": "IN", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "MOXIFLOXACIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021085", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOXIFLOXACIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TERIZIDONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MG, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TERIZIDONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE" } ], "patientagegroup": "5", "patientonsetage": "45", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": null } ], "summary": null }, "primarysource": { "literaturereference": "Laxmikant Ramkumarsingh Tomar1 , Neha Pandita1,. Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis. Tropical Doctor. 2021;1-3", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "1", "reportercountry": "IN" }, "primarysourcecountry": "IN", "receiptdate": "20211227", "receivedate": "20211227", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20233073, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 2, "transmissiondate": "20220303" }, { "companynumb": "IN-MACLEODS PHARMACEUTICALS US LTD-MAC2021033764", "fulfillexpeditecriteria": "1", "occurcountry": "IN", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Tablet", "drugdosagetext": "1 GRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "AMIKACIN" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 GRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMIKACIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PYRAZINAMIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "212541", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Tablet", "drugdosagetext": "1.5 GRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRAZINAMIDE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ISONIAZID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Tablet", "drugdosagetext": "300 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ISONIAZID" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM, QD (TABLETS)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MOXIFLOXACIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOXIFLOXACIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MILLIGRAM, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TERIZIDONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MILLIGRAM, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TERIZIDONE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug-induced liver injury", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Tomar LR, Pandita N, Arya S, Agrawal CS.. Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis. Tropical Doctor. 2021;1-3", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "1", "reportercountry": "IN" }, "primarysourcecountry": "IN", "receiptdate": "20211221", "receivedate": "20211221", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20211433, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": null, "fulfillexpeditecriteria": "1", "occurcountry": "IN", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "205517", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 GRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ISONIAZID" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "300 MILLIGRAM, OD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "300", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ISONIAZID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "AMIKACIN" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 GRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMIKACIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 GRAM, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 GRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MOXIFLOXACIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 GRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOXIFLOXACIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TERIZIDONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 GRAM, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": "Disseminated tuberculosis", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TERIZIDONE" } ], "patientagegroup": null, "patientonsetage": "45", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Posterior reversible encephalopathy syndrome", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug-induced liver injury", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypomagnesaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Tomar LR, Pandita N, Arya S, Agrawal CS. Linezolid-Associated Posterior Reversible Leuco-encephalopathy Syndrome in a Patient with Disseminated Tuberculosis. Tropical Doctor. 2021;Unknown:1-3", "literaturereference_normalized": "linezolid associated posterior reversible leuco encephalopathy syndrome in a patient with disseminated tuberculosis", "qualification": "1", "reportercountry": "IN" }, "primarysourcecountry": "IN", "receiptdate": "20220111", "receivedate": "20220111", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20320203, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" } ]

{ "abstract": "Classification of myeloproliferative neoplasms is based on hematologic, histopathologic, and molecular characteristics, including the BCR-ABL1 and JAK2 V617F or MPL and CALR. Although the different gene mutations ought to be mutually exclusive, several cases with co-occurring BCR-ABL1 and JAK2 V617F or CALR have been identified with a frequency of 0.2-2.5% in the European population. The tyrosine kinase abnormalities appeared to affect independent subclones because imatinib mesylate (IM) treatment induced Ph+-CML remission, whereas the JAK2V617F clone either persisted or clinically expanded after a major response of Ph+-clone. Allogeneic stem cell transplantation is at present the only potentially curative therapy for these patients after therapy with ruxolitinib and TKI inhibitor. We describe the case of 3 young people treated in our institution for the coexistence of BCR/ABL chronic myeloid leukemia and another Philadelphia chromosome-negative (Ph-) Chronic myeloproliferative disease. They received ruxolitinib, imatinib/nilotinib, and allogeneic transplantation with safe and efficient results.", "affiliations": "Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.;Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.;Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.;Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.;Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.;Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.;Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.;Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.;Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.;Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.", "authors": "Sora|Federica|F|;Chiusolo|Patrizia|P|;Autore|Francesco|F|;Giammarco|Sabrina|S|;Laurenti|Luca|L|;Innocenti|Idanna|I|;Metafuni|Elisabetta|E|;Galli|Eugenio|E|;Bacigalupo|Andrea|A|;Sica|Simona|S|", "chemical_list": null, "country": "Italy", "delete": false, "doi": "10.4084/MJHID.2021.062", "fulltext": "\n==== Front\nMediterr J Hematol Infect Dis\nMediterr J Hematol Infect Dis\nMediterranean Journal of Hematology and Infectious Diseases\nMediterranean Journal of Hematology and Infectious Diseases\n2035-3006\nUniversità Cattolica del Sacro Cuore\n\n10.4084/MJHID.2021.062\nmjhid-13-1-e2021062\nOriginal Article\nIs Allogeneic Transplantation an Option in Patients Affected by Concurrent Myelofibrosis and Chronic Myeloid Leukemia (CML)?\nSora Federica 12\nChiusolo Patrizia 12\nAutore Francesco 1\nGiammarco Sabrina 1\nLaurenti Luca 12\nInnocenti Idanna 1\nMetafuni Elisabetta 1\nGalli Eugenio 1\nBacigalupo Andrea 12\nSica Simona 12\n1 Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy\n2 Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universita Cattolica del Sacro Cuore, Roma, Italy\nCorrespondence to: Federica Sora, MD. Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Universita Cattolica del Sacro Cuore, Roma, Italy. Largo Gemelli 1, 00168 Roma. Tel: 0039-6-30154180. E-mail: federica.sora@unicatt.it\n2021\n01 11 2021\n13 1 e202106211 7 2021\n15 10 2021\n2021\nhttps://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\nClassification of myeloproliferative neoplasms is based on hematologic, histopathologic, and molecular characteristics, including the BCR-ABL1 and JAK2 V617F or MPL and CALR. Although the different gene mutations ought to be mutually exclusive, several cases with co-occurring BCR-ABL1 and JAK2 V617F or CALR have been identified with a frequency of 0.2–2.5% in the European population. The tyrosine kinase abnormalities appeared to affect independent subclones because imatinib mesylate (IM) treatment induced Ph+-CML remission, whereas the JAK2V617F clone either persisted or clinically expanded after a major response of Ph+-clone.\n\nAllogeneic stem cell transplantation is at present the only potentially curative therapy for these patients after therapy with ruxolitinib and TKI inhibitor. We describe the case of 3 young people treated in our institution for the coexistence of BCR/ABL chronic myeloid leukemia and another Philadelphia chromosome-negative (Ph−) Chronic myeloproliferative disease. They received ruxolitinib, imatinib/nilotinib, and allogeneic transplantation with safe and efficient results.\n\nChronic myeloid leukemia\nMyelofibrosis\nJAK\nAllogeneic transplantation\n==== Body\npmcIntroduction\n\nChronic myeloproliferative diseases (CMPDs) are clonal disorders of hematopoietic stem cells classified according to their clinical and phenotypical features and genetic aberrations.1 CMPDs are usually divided according to the presence of Philadelphia chromosome/BCR–ABL fusion (Ph+) as chronic myeloid leukemia (CML) and the Philadelphia chromosome-negative (Ph−) CMPD (polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF). In the Ph negative category, a crucial role is linked to detecting the three major subcategories of gene mutations: JAK2/CALR/MPL mutation. Recently, some authors simultaneously reported on few well-documented cases with concurrent JAK2V617F and BCR–ABL translocation..2–7 The tyrosine kinase abnormalities appeared to affect independent subclones because imatinib mesylate (IM) treatment induced Ph+-CML remission, whereas the JAK2V617F clone either persisted or clinically expanded after a major response of Ph+-CML to IM.8–9\n\nAllogeneic hematopoietic cell transplantation (HCT) is currently the only treatment modality that offers potentially curative therapy for patients with myeloproliferative neoplasms (MPN) being largely abandoned in Ph+ MPD in the era of targeted therapy but still valid in primary myelofibrosis (PMF) and secondary myelofibrosis developing after polycythemia vera (post-PV MF) or essential thrombocythemia (post-ET MF) based on attributable risk score and patient’s profile.\n\nMolecular studies showed the prognostic role of “driver mutations” as JAK2, MPL1, and CALR and additional somatic DNA mutations, including ASXL1, EZH2, IDH1/2, and SRSF2. Thus, the combination and number of mutations are more relevant than a given single mutation. Mutations also appear to impact the outcome of hematopoietic cell transplantation (HCT). The availability of the JAK 1/2 inhibitor ruxolitinib, the first agent approved for molecularly targeted therapy in patients with PMF or with PV intolerant to other therapies, has modified treatment strategies for these patients. Randomized trials have shown that ruxolitinib, in addition to alleviating symptoms and reducing splenomegaly in a large proportion of patients, also prolongs survival.10–11\n\nSince the rarity of concomitant presence of BCR-ABL positive CML and myelofibrosis, only a few data are available of the combination therapy and stem cell transplantation (SCT) on the role on the outcome.\n\nThis report is the first to describe patients diagnosed with two concomitant chronic myeloproliferative diseases treated with tyrosine-kinase inhibitors and JAK2 inhibitors or anagrelide for whom allogeneic SCT was either performed or planned.\n\nPatients and Methods\n\nCase report 1\n\nIn 1997, a 24-year-old woman presented with elevated platelet counts without clinical features. Bone marrow morphological analysis was performed, and a diagnosis of ET was made. Cytogenetic analysis showed normal karyotype, and the molecular study was negative for BCR-ABL1 rearrangement. The patient was firstly treated with interferon-alpha with benefits, and a successful pregnancy was carried out. In 2003, after an increase of hematocrit value over 50%, she received five phlebotomies, and anagrelide was introduced. JAK2 V617F mutation was detected for the first time in 2008. Bone marrow biopsy, performed in 2012, documented post-ET myelofibrosis (IMF-2), and the JAK2 V617F allelic ratio was 73%. While on anagrelide, in January 2014, she showed persistent leucocytosis, and PCR analysis showed a BCR-ABL1 transcript (b3a2). Cytogenetic analysis showed a normal karyotype; FISH analysis confirmed t(9:22) translocation. As a consequence, imatinib therapy was administered at 400 mg daily, associated with anagrelide. Major molecular response (MMR) was rapidly achieved at six months and deep molecular response (DMR) (MR4.5) at 12 months, with no effect on the myelofibrosis. The allelic ratio during imatinib and anagrelide treatment was checked every three months and remained stable over 50% for all the period. NGS analysis for subclonal mutations was performed, and we found SF3B1 c.1849G>T with a low VAF (9%).\n\nIn June 2018, anagrelide was discontinued because of progressive anemia while in DMR for BCR-ABL transcript with increasing bone marrow fibrosis. Shortly after anagrelide discontinuation, thrombocytosis required hydroxyurea and in December 2018 bone marrow biopsy showed blastic evolution (17% of blasts) of post–ET myelofibrosis and acquisition of cytogenetic abnormality in 17 out of 20 metaphases (46,XX,−12,+der(12)(12qter->q10::8q10->qter),−4,+22,del(20)(q11)). In July 2019, she received an allogeneic peripheral blood SCT from an HLA-matched unrelated donor (MUD) after a TBF conditioning regimen.12 The status at ASCT was DMR of CML, JAK2 V617F mutation with allele burden of 58%. Full donor chimerism was documented at day+30 after transplant. The patient is alive in complete remission of both diseases with stable full donor chimerism at 24 months after SCT without signs of GVHD.\n\nCase report 2\n\nIn July 2014, a 52-year-old man presented with splenomegaly and elevated white blood cell count (170000/microl). He also showed splenomegaly (20 cm below costal margin), fatigue, peripheral edema, and weight body loss (10 kg in six months). The molecular study disclosed BCR-ABL rearrangement (b3a2), and a diagnosis of CML chronic phase was made according to ELN criteria.13 Bone marrow biopsy confirmed the diagnosis of a myeloproliferative disorder with marked fibrosis and sclerosis. Cytogenetic analysis showed a normal karyotype, and the molecular study was negative for the JAK2 V617F mutation. Sokal, Hasford, EUTOS risk score were high. The patient started Nilotinib 600mg with a rapid peripheral blood cell count normalization and reduction of the spleen size. After six months, despite MMR for BCR-ABL transcript, systemic symptoms and splenomegaly were unchanged, and bone marrow fibrosis persisted. In February 2015, Calreticulin (CALR) gene type1 was detected. The analysis was performed with PCR followed by capillary electrophoresis, and the ratio between the mutated gene and wild type (30%) remained stable from diagnosis until transplant. Moreover, NGS analysis for subclonal mutations was performed, and the following genes were found to be mutated: ASXL1 c.302C>T (VAF 37%) and ZRSR2 c.5558-1G>T (VAF 10%). He added ruxolitinib at the dose of 20mg/d. After three months of ruxolitinib, there was a mild decrease in splenomegaly, but no significant change in bone marrow fibrosis was detected. However, a dose reduction of ruxolitinib and nilotinib was required to manage hematologic toxicity (grade 3 anemia according to CTCAE). In March 2019, constitutional symptoms increased, and severe hepatomegaly developed, and the patient became transfusion dependent. The patient was eligible for allogeneic SCT and received peripheral blood SCT from a MUD with TBF as a conditioning regimen. At day +30, a mixed chimaerism was found (88%), while at day +60, full donor chimaerism was obtained. The posttransplantation course was remarkable for acute renal and respiratory failure, followed by several complications, including CMV, cardiac failure, and GVHD. The patient died from multi-organ failure seven months after SCT and no evidence of diseases.\n\nCase report 3\n\nIn June 2015, a 58-year-old woman was referred from another hospital with chronic phase CML diagnosed two years before, low Sokal risk and BCR-ABL b3a2. Despite deep molecular response (MR4) during treatment with nilotinib, thrombocytosis persisted. At the time of our evaluation, white blood cell count and hemoglobin level were normal, but platelet count was persistently high (600 *109/l) despite normal iron balance. For these reasons, she was re-evaluated, and JAK2 V617F mutation was detected, and the allelic burden remained stable over 50%. Cytogenetic analysis showed normal karyotype. Spleen size was enlarged, and bone marrow biopsy showed marked fibrosis. Due to the patient’s refusal, ruxolitinib was not started. A MUD search was initiated. Progressive splenomegaly and fatigue further developed in 2018. NGS analysis was performed, and the following subclonal mutations were found: ASXL1 c.2110G>A (VAF 48%), TET2 c.5162T>C, c.5623T>C and c86C>G with VAF of 47%, 38% and 47% respectively. Finally, in February 2019, ruxolitinib was started at the dose of 20mg without hematologic toxicity, control of fatigue, but no spleen size reduction. This patient was classified as DIPSS grade 2 MFI; she was still in DMR for CML and, in March 2021, received an allogeneic SCT from a MUD. Full donor chimerism was documented at day+30 after transplant. The patient is alive in complete remission with stable full donor chimerism at four months after SCT without signs of GVHD.\n\nDiscussion\n\nFrom 2007 onward, almost 70 cases of coexistent MPD have been reported in the medical literature. Their incidence varies from 0.2% to 2.5% with a median age of 68 years, predominantly males, and some authors suggested that the incidence may vary according to different phases of CML.14 The first report, published by Kramer et al.3 in 2007, describes a 50 years old man who, three years after CML diagnosis successfully treated with imatinib and in cytogenetic and molecular response, developed an increase in LDH plasma level and a decrease in platelet count. The patient also presented an enlarged spleen and bone marrow fibrosis and a positive JAK2-V617F mutation. In this report, the author showed that bone marrow fibrosis was not a consequence of progressive CML. Also, imatinib, a selective inhibitor of ABL, KIT, and PDGF receptor, reduces the content of bone marrow fibers CML. However, the response to imatinib could accelerate the outgrowth of IMF, modifying the balance of the concurrent MPD. Furthermore, JAK2 mutation was already present at CML diagnosis in a retrospective analysis of frozen samples.\n\nIn 2007, Inami et al. and Bornauser et al.4–5 published the cases of few patients simultaneously presenting JAK2-V617F mutation and BCR-ABL rearrangement. Also in this case, molecular abnormalities seem to affect two different clones, and the molecular response to imatinib induced the clinical manifestation of myelofibrosis, shifting the balance in favor of the JAK2 V617F clone. From the HANNOVER registry in 2008, Hussein et al.2 reported four additional cases. Finally, Pieri et al.15 described double mutated myeloproliferative disease in a cohort of CML patients with an incidence of 8 out of 314 patients in a chronic phase (2.55%).\n\nThe optimal first-line treatment for these patients was not clearly described, but the response of BCR-ABL burden to different TKI (imatinib, dasatinib, nilotinib) was optimal in all patients reported. The increase of JAK allele burden following the successful treatment of CML was characterized by the appearance of constitutional symptoms and spleen enlargement resulting from proliferative competition between the two clones. More recently, Iurlo et al. and Zhou et al.6–8 described additional cases of concomitant MPD in whom the use of combination therapy with ruxolitinib, associated with imatinib or dasatinib, in three patients was safe and effective, but with no data with a prolonged follow up are available.\n\nFinally, Martin Cabrera et al.9 analyzed all patients with suspected MPD for BCR ABL, JAK2 V617F, and MPL by RT PCR analysis, they found 23 out 10875 patients positive at diagnosis for BCR ABL and JAK2 V617F (0.2%), but no patients positive for MPL and BCR ABL. In these patients, the molecular analysis suggested that JAK2 V617F and BCR-ABL mutations developed from different clones except for two patients in which common ancestors were supposed. Additional genetic abnormalities were also reported suggesting genomic instability.14–15\n\nThus there are patients with concurrent MPD, although rare, two different clones are involved, the clinical presentation may vary being CML or JAK2 V617F or MPD alternatively detected first or during treatment, suggesting a shift in favor of the expansion of one clone over the other particularly when CML was the prior disease treated with TKI. Latency seems to be different; in fact, a decade in average was necessary for CML to occur after JAK2 + MPD but only 5.4 years when JAK2 + MPD followed CML in a recent analysis from Bader et al.17\n\nIn this scenario, we found three additional patients with concurrent MPD with JAK2 mutation in 2 cases and 1 case expressing CALR. CML was easy to manage either with imatinib or nilotinib, but JAK2 V617F or Calr MPD was uneasily controlled by conventional therapy, including hydroxiurea, transfusions, and JAK2 inhibitors such as ruxolitinib in all patients. All of them developed overt IMF. Considering their age and despite deep control of CML, all of them were considered eligible for allogeneic HSCT as the only curative option in intermediate- or high risk myelofibrosis. In the first patient, the indication for HSCT was supported by the blastic phase. Meanwhile, in the other ones, the presence of detrimental NGS mutation reinforced the HSCT need.\n\nEven if partially appropriate, the application of the current risk score, including DIPSS and MySEe, considering CML as a concurrent disease, classified all patients in either intermediate or high risk category. Even if this subset of patients is rare, they require attention at diagnosis, for accurate classifications and prognosis, and during treatment, if new symptoms develop, such as splenomegaly or thrombocytosis, etc. Evolution to myelofibrosis prevails over CML. The hybrid condition is not included in the current treatment algorithm of treatment and indication for transplantation, and it deserves case-by-case evaluation and referral for HSCT.18–19 HSCT is associated with high transplant-related mortality and morbidity particularly in patients over 55 years.\n\nAcknowledgments\n\nThe authors acknowledge the support of ‘Centro di Ricerca sulle cellule staminali hemopoietic e le terapie cellulari “Universita’ Cattolica S. Cuore, Roma”.\n\nCompeting interests: The authors declare no conflict of Interest.\n==== Refs\nReferences\n\n1 Tefferi A Thiele J Orazi A Kvasnicka HM Barbui T Hanson CA Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel Blood 2007 110 1092 1097 10.1182/blood-2007-04-083501 17488875\n2 Hussein K Bock O Seegers A Flasshove M Henneke F Busche G myelofibrosis evolving during Imatinib treatment of a chronic myeloproliferative disease with co-existing BCR-ABL translocation and JAK2V617F mutation Blood 2007 109 4106 4107 10.1182/blood-2006-12-061135 17449802\n3 Kramer A Reiter A Kruth J Erben P Hochhaus A Muller M JAK2-V617F mutation in a patient with Philadelphia-chromosome-positive chronic myeloid leukaemia Lancet Oncol 2007 8 658 660 10.1016/S1470-2045(07)70206-1 17613428\n4 Bornhauser M Mohr B Oelschlaegel U Bornhauser P Jacki S Ehninger G Concurrent JAK2(V617F) mutation and BCR-ABL translocation within committed myeloid progenitors in myelofibrosis Leukemia 2007 21 1824 1826 10.1038/sj.leu.2404730 17476275\n5 Inami M Inokuchi K Okabe M Kosaka F Mitamura Y Yamaguchi H Polycythemia associated with the JAK2V617F mutation emerged during treatment of chronic myelogenous leukemia Leukemia 2007 21 1103 1104 10.1038/sj.leu.2404591 17301812\n6 Iurlo A Gianelli U Rapezzi D Cattaneo D Fermo E Binda F Imatinib and ruxolitinib association: first experience in two patients Haematologica 2014 6 e76 7 10.3324/haematol.2013.102525 24633869\n7 Soderquist CR Ewalt MD Czuchlewski DR Geyer JT Rogers HJ Hsi ED Myeloproliferative neoplasms with concurrent BCR-ABL1 translocation and JAK2 V617F mutation: a multi-institutional study from the bone marrow pathology group Mod Pathol 2018 5 690 704 10.1038/modpathol.2017.182 29327708\n8 Zhou A Knoche EM Engle EK Fisher DA Oh ST Concomitant JAK2 V617F-positive polycythemia vera and BCR-ABL-positive chronic myelogenous leukemia treated with ruxolitinib and dasatinib Blood Cancer J 2015 10 e351 10.1038/bcj.2015.77 26430722\n9 Martin-Cabrera P Haferlach C Kern W Schnittger S Haferlach T BCR-ABL1-positive and JAK2 V617F-positive clones in 23 patients with both aberrations reveal biologic and clinical importance Br J Haematol 2017 1 1 135 139 10.1111/bjh.13932 26847954\n10 Verstovsek S Mesa RA Gotlib J Levy RS Gupta V DiPersio JF A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis N Engl J Med 2012 366 799 807 10.1056/NEJMoa1110557 22375971\n11 Harrison C Kiladjian J Haifa K Gisslinger H Waltzman R Stalbovskaya V JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis N Engl J Med 2012 366 787 798 10.1056/NEJMoa1110556 22375970\n12 Sora F Grazia CD Chiusolo P Raiola AM Bregante S Mordini N Allogeneic Hemopoietic Stem Cell Transplants in Patients with Acute Myeloid Leukemia (AML) Prepared with Busulfan and Fludarabine (BUFLU) or Thiotepa, Busulfan, and Fludarabine (TBF): A Retrospective Study Biol Blood Marrow Transplant 2020 4 26 4 698 703 10.1016/j.bbmt.2019.12.725 31875522\n13 Baccarani M Saglio G Goldman J Hochhaus A Simonsson B Appelbaum F Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet Blood 2006 108 1809 20 10.1182/blood-2006-02-005686 16709930\n14 Makishima H Jankowska AM McDevitt MA O’Keefe C Dujardin S Cazzolli H CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia Blood 2011 21 e198 206 10.1182/blood-2010-06-292433 21346257\n15 Pieri L Spolverini A Scappini B Occhini U Birtolo S Concomitant occurrence of BCR-ABL and JAK2V617F mutation Blood 2011 22 12 3445 6 10.1182/blood-2011-07-365007 21940831\n16 Dogliotti I Fava C Serra A Gottardi E Daraio F Carnuccio F CALR-positive myeloproliferative disorder in a patient with Ph-positive chronic myeloid leukemia in durable treatment-free remission: a case report Stem Cell Investig 2017 6 23 4 57 10.21037/sci.2017.06.02 28725653\n17 Bader G Dreiling B Concurrent JAK2-Positive Myeloproliferative Disorder and Chronic Myelogenous Leukemia: A Novel Entity? A Case Report With Review of the Literature J Investig Med High Impact Case Rep 2019 Jan-Dec 7 2324709619832322 10.1177/2324709619832322 30803277\n18 Jain T Mesa RA Palmer JM Allogeneic Stem Cell Transplantation in Myelofibrosis Biol Blood Marrow Transplant 2017 9 1429 1436 10.1016/j.bbmt.2017.05.007 28499938\n19 Tiribelli M Palandri F Sant’Antonio E Breccia M Bonifacio M The role of allogeneic stem-cell transplant in myelofibrosis in the era of JAK inhibitors: a case-based review Bone Marrow Transplant 2020 4 708 716 10.1038/s41409-019-0683-1 31534197\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "2035-3006", "issue": "13(1)", "journal": "Mediterranean journal of hematology and infectious diseases", "keywords": "Allogeneic transplantation; Chronic myeloid leukemia; JAK; Myelofibrosis", "medline_ta": "Mediterr J Hematol Infect Dis", "mesh_terms": null, "nlm_unique_id": "101530512", "other_id": null, "pages": "e2021062", "pmc": null, "pmid": "34804436", "pubdate": "2021", "publication_types": "D016428:Journal Article", "references": "22375970;17488875;17613428;31875522;30803277;29327708;28499938;17301812;16709930;17476275;22375971;26430722;31534197;17449802;21940831;21346257;28725653;26847954;24633869", "title": "Is Allogeneic Transplantation an Option in Patients Affected by Concurrent Myelofibrosis and Chronic Myeloid Leukemia (CML)?", "title_normalized": "is allogeneic transplantation an option in patients affected by concurrent myelofibrosis and chronic myeloid leukemia cml" }

[ { "companynumb": "IT-002147023-NVSC2022IT021751", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "RUXOLITINIB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "202192", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Tablet", "drugdosagetext": "20 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "Chronic myeloid leukaemia", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RUXOLITINIB" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "NILOTINIB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Chronic myeloid leukaemia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NILOTINIB" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Anaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Sora F, Chiusolo P, Autore F, Giammarco S, Laurenti L, Innocenti I et al... Is allogeneic transplantation an option in patients affected by concurrent myelofibrosis and chronic myeloid leukemia (CML)?.. MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES.. 2021;13(1):e2021062(1-5)", "literaturereference_normalized": "is allogeneic transplantation an option in patients affected by concurrent myelofibrosis and chronic myeloid leukemia cml", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20220214", "receivedate": "20220214", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20471886, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220424" } ]

{ "abstract": "There are several classes of medications that can cause prolongation of the corrected QT (QTc) interval and potentially Torsades de Pointes (TdP). Most of these medications are commonly used in the emergency department, and interaction between these medications increases the risk of this iatrogenic complication. We describe a patient on methadone therapy who developed TdP after she received metoclopramide and metronidazole. Interaction between different classes of medications can increase the risk of QTc prolongation and TdP. Awareness of this condition and its risk factors need continuous reinforcement among all hospital personnel to reduce the risk of this life-threatening complication.", "affiliations": "Department of Internal Medicine, Mayo Clinic, 3500 San Pablo Road S, Jacksonville, FL 32224, USA.;Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.;Department of Cardiology, Yale University School of Medicine, New Haven, CT 06510, USA.", "authors": "Gnanapandithan|Karthik|K|0000-0003-0463-5225;Karthik|Nishrutha|N|;Gerber|Jaime|J|", "chemical_list": null, "country": "Switzerland", "delete": false, "doi": "10.3390/clinpract11010015", "fulltext": "\n==== Front\nClin Pract\nClin Pract\nclinpract\nClinics and Practice\n2039-7275\n2039-7283\nMDPI\n\n33562182\n10.3390/clinpract11010015\nclinpract-11-00015\nCase Report\nMethadone, Metoclopramide and Metronidazole Interaction Causing Torsades de Pointes\nhttps://orcid.org/0000-0003-0463-5225\nGnanapandithan Karthik 1*\nKarthik Nishrutha 2\nGerber Jaime 3\n1 Department of Internal Medicine, Mayo Clinic, 3500 San Pablo Road S, Jacksonville, FL 32224, USA\n2 Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Nithik23@gmail.com\n3 Department of Cardiology, Yale University School of Medicine, New Haven, CT 06510, USA; Jaime.Gerber@yale.edu\n* Correspondence: Gnanapandithan.Karthik@mayo.edu; Fax: +1-903-953-2848\n07 2 2021\n3 2021\n11 1 101105\n04 12 2020\n04 2 2021\n© 2021 by the authors.\n2021\nLicensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).\nThere are several classes of medications that can cause prolongation of the corrected QT (QTc) interval and potentially Torsades de Pointes (TdP). Most of these medications are commonly used in the emergency department, and interaction between these medications increases the risk of this iatrogenic complication. We describe a patient on methadone therapy who developed TdP after she received metoclopramide and metronidazole. Interaction between different classes of medications can increase the risk of QTc prolongation and TdP. Awareness of this condition and its risk factors need continuous reinforcement among all hospital personnel to reduce the risk of this life-threatening complication.\n\nQT prolongation\nTorsades de Pointes\nmetoclopramide\nmetronidazole\nmethadone\ndrug-induced Torsades de Pointes\n==== Body\n1. Introduction\n\nThere are multiple factors that can affect myocardial repolarization and result in prolongation of the corrected QT (QTc) interval [1,2]. Abnormal prolongation of the QTc interval can result in Torsades de Pointes (TdP), which is a type of polymorphic ventricular tachyarrhythmia. Most of the medications that were initially described to affect the QT interval were antiarrhythmics; however, a large number of non-cardiac drugs are now known to be associated with this adverse event. In recent times, drug-induced long QT syndrome (LQTS) is the most important cause of the withdrawal of marketed drugs [1]. The interaction can occur due to multiple drugs that prolong the QT interval or a medication that potentiates the effect of another by affecting its metabolism. We describe a case in which interaction between multiple medications, namely methadone, metoclopramide and metronidazole, resulted in TdP.\n\n2. Case Report\n\nA 50-year-old female with a medical history of acquired immunodeficiency syndrome not compliant with anti-retroviral therapy, polysubstance abuse and opioid dependence on methadone maintenance was brought in to the emergency department (ED) after she was found vomiting and confused in the streets. She reported using heroin and cocaine. On evaluation, she had sinus bradycardia, with a heart rate of 44 per minute, respiratory rate of 18 per minute and blood pressure of 128/80 mm Hg. Examination revealed a lethargic patient with no focal neurological deficits, clear lungs, sinus rhythm with no murmurs and soft abdomen. Laboratory testing showed a serum potassium of 3.5 meq/L, magnesium 2.1 meq/L, creatinine 0.5 mg/dL. Electrocardiogram (EKG) revealed sinus bradycardia with a rate of 40, a QT interval of 512 ms and a corrected QT (QTc) of 460 ms (Figure 1A). A non-contrast computerized tomography of the head and a chest radiograph did not show any acute abnormality. Her urine toxicology was positive for methadone, cocaine and opioids. Her mental status slowly improved during her stay in the ED; however, she started to have nausea and vomiting. She received intravenous (IV) metoclopramide 10 mg. She developed a fever of 101F during her stay in the ED. She was given IV ceftriaxone and metronidazole for suspected aspiration pneumonia. Metronidazole was started about 45 min after the metoclopramide was given and was slowly infused over 30 min. Shortly after the metronidazole infusion was stopped, she was unresponsive and the cardiac monitor (Figure 1B,C) revealed Torsades de Pointes (TdP). She was defibrillated with a return to sinus rhythm. Follow up EKG showed sinus rhythm with a QTc of 542 ms. Cardiology was consulted. IV potassium chloride and magnesium sulfate were given. Later, an echocardiogram showed an ejection fraction of 47%, normal right ventricular function and no valvular abnormalities. Over the next two days, there were no significant arrhythmias and the QTc returned to 432 ms.\n\n3. Discussion\n\nAbnormal repolarization pattern resulting from prolongation of QT interval or abnormal morphology of the T-wave can result in TdP [1,2]. Congenital and acquired causes of long QT syndrome (LQTS) can predispose to TdP. Apart from a prolonged QT, the presence of bradycardia and beat-to-beat variability [3,4] in QT are other known risk factors for TdP. Medications that affect cardiac repolarization are a common cause of acquired LQTS. In the acquired variant, a typical sequence of events has been described in the EKG [2]. It starts with a ventricular premature complex or an ectopic beat that results in a compensatory pause. This is followed by a sinus beat that usually has a long QTc, terminating in a ventricular extrasystole that usually starts the TdP. It may be self-limiting, in which case it can cause syncope, or if sustained, it can degenerate into ventricular fibrillation resulting in a cardiac arrest. The EKG strip in our patient (Figure 1A) shows the variability in QT interval and prolongation of QT before the onset of TdP.\n\nDrug-induced LQTS that can potentially lead to TdP and ventricular fibrillation arrest is a well-known but underestimated problem. Antiarrhythmics, psychiatric medications, antihistaminics, antibiotics, antifungals and antiemetics are some of the common classes of drugs that can cause prolongation of QTc. All these drugs are commonly used in the emergency department and inpatient setting [5]. There are reports of metoclopramide associated TdP [6,7], mostly in patients with underlying heart disease or renal failure. Cocaine [8,9] and methadone [10] are also associated with LQTS. Other cardiac effects of methadone predisposing to TdP include bradycardia and QT dispersion [11]. Opioids vary in their tendency to predispose to cardiac arrhythmias. Methadone has been identified as a higher risk agent that can increase the risk of long QT related arrhythmias even in lower doses [12], and hence, a close monitoring of these individuals is recommended. Methadone is metabolized in the liver, primarily by CYP3A4, with CYP 2D6 and CYP1A2 also being involved [13]. Metronidazole is an inhibitor of CYP2C9 and CYP3A4 isoenzymes and can interact with drugs [14] causing LQTS and TdP. Older age, female sex, underlying structural heart disease, recent myocardial infarction and family history of sudden cardiac death are known risk factors [1,15]. Simultaneous use of drugs that can prolong QT interval is a significant risk factor. Use of these drugs in patients on enzyme (cytochrome P450) inhibitors or those with electrolyte abnormalities (hypokalemia, hypocalcemia and hypomagnesemia) can also predispose to TdP. Judicious use of these drugs in recommended doses, minimizing use in patients with pre-existing prolonged QT interval or other cardiac risk factors can help in reducing this life-threatening iatrogenic adverse event. There are several online tools such as RxList, WebMD and Medscape that are available to health care professionals to check interactions between medications. CredibleMeds [16] is a website with a free smartphone app that offers information on general drug interactions and a dedicated section on QTc interactions.\n\nTdP with hemodynamic instability is treated with defibrillation. IV magnesium sulfate is the first-line therapy [17,18] and is effective in patients with normal serum magnesium levels as well. Other interventions include identification and discontinuation of the culprit medications and correction of electrolyte abnormalities, especially hypokalemia [18]. Cardiac pacing and isoproterenol are reserved for refractory cases [17,18].\n\n4. Conclusions\n\nThough well known, drug interactions leading to LQTS and TdP remain a dangerous yet underestimated problem. In patients on methadone or those with a prolonged QTc, caution should be exercised in the concurrent use of other medications that can interact to increase the risk of TdP. High-risk patients need to be on close cardiac monitoring when these drugs are being administered. Continued reinforcement of this condition among all hospital personnel can increase awareness and help reduce the incidence of this life-threatening complication.\n\nAuthor Contributions\n\nK.G.—manuscript preparation and review of literature; N.K.—manuscript preparation and review of literature; J.G.—review of manuscript. All authors have read and agreed to the published version of the manuscript.\n\nFunding\n\nThis research received no external funding.\n\nInformed Consent Statement\n\nInformed consent was obtained from the patient in the report.\n\nConflicts of Interest\n\nThe authors declare no conflict of interest. The authors have no financial disclosures.\n\nFigure 1 (A) Electrocardiogram on admission shows prolonged corrected QT (QTc) and variability in QT interval. (B) Onset of Torsades de Pointes (TdP) shortly after metronidazole infusion. (C) Persistent TdP requiring defibrillation.\n\nPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n\n1. Roden D.M. Drug-Induced Prolongation of the QT Interval N. Engl. J. Med. 2004 350 1013 1022 10.1056/NEJMra032426 14999113\n2. Yap Y.G. Camm A.J. Drug induced QT prolongation and torsades de pointes Heart 2003 89 1363 1372 10.1136/heart.89.11.1363 14594906\n3. Drew B.J. Ackerman M.J. Funk M. Gibler W.B. Kligfield P. Menon V. Philippides G.J. Roden D.M. Zareba W. Prevention of torsade de pointes in hospital settings: A scientific statement from the American heart association and the American college of cardiology foundation Circulation 2010 121 1047 1060 10.1161/CIRCULATIONAHA.109.192704 20142454\n4. Baumert M. Porta A. Vos M.A. Malik M. Couderc J.P. Laguna P. Piccirillo G. Smith G.L. Tereshchenko L.G. Volders P.G. QT interval variability in body surface ECG: Measurement, physiological basis, and clinical value: Position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology Europace 2016 18 925 944 26823389\n5. Pourmand A. Mazer-Amirshahi M. Chistov S. Sabha Y. Vukomanovic D. Almulhim M. Emergency department approach to QTc prolongation Am. J. Emerg. Med. 2017 35 1928 1933 10.1016/j.ajem.2017.08.044 28855066\n6. Chou C.C. Wu D. Torsade de pointes induced by metoclopramide in an elderly woman with preexisting complete left bundle branch block Chang. Gung. Med. J. 2001 24 805 809 11858397\n7. Siddique S.M. Shariff N. Vesuwala N. Hafiz T. Metoclopramide as a possible cause of prolonged QT syndrome and torsade de pointes in a patient with heart failure and renal insufficiency Ann. Intern. Med. 2009 150 502 504 10.7326/0003-4819-150-7-200904070-00016 19349637\n8. Taylor D. Parish D. Thompson L. Cavaliere M. Cocaine induced prolongation of the QT interval Emerg. Med. J. 2004 21 252 253 10.1136/emj.2002.003251 14988369\n9. Magnano A.R. Talathoti N.B. Hallur R. Jurus D.T. Dizon J. Holleran S. Bloomfield D.M. Collins E. Garan H. Effect of Acute Cocaine Administration on the QTc Interval of Habitual Users Am. J. Cardiol. 2006 97 1244 1246 10.1016/j.amjcard.2005.11.046 16616034\n10. Krantz M.J. Martin J. Stimmel B. Mehta D. Haigney M.C. QTc interval screening in methadone treatment Ann. Intern. Med. 2009 150 387 395 10.7326/0003-4819-150-6-200903170-00103 19153406\n11. Alinejad S. Kazemi T. Zamani N. Hoffman R.S. Mehrpour O. A systematic review of the cardiotoxicity of methadone EXCLI J. 2015 14 577 600 26869865\n12. Behzadi M. Joukar S. Beik A. Opioids and Cardiac Arrhythmia: A Literature Review Med. Princ. Pract. 2018 27 401 414 10.1159/000492616 30071529\n13. Ferrari A. Coccia C.P.R. Bertolini A. Sternieri E. Methadone—Metabolism, pharmacokinetics and interactions Pharmacol. Res. 2004 50 551 559 10.1016/j.phrs.2004.05.002 15501692\n14. Kounas S.P. Letsas K.P. Sideris A. Efraimidis M. Kardaras F. QT interval prolongation and torsades de pointes due to a coadministration of metronidazole and amiodarone Pacing Clin. Electrophysiol. 2005 28 472 473 10.1111/j.1540-8159.2005.09348.x 15869686\n15. Franchi C. Ardoino I. Rossio R. Nobili A. Biganzoli E.M. Marengoni A. Marcucci M. Pasina L. Tettamanti M. Corrao S. Prevalence and Risk Factors Associated with Use of QT-Prolonging Drugs in Hospitalized Older People Drugs Aging 2016 33 53 61 10.1007/s40266-015-0337-y 26693921\n16. Woosley R.L. Black K. Heise C.W. Romero K. CredibleMeds.org: What does it offer? Trends Cardiovasc. Med. 2018 28 94 99 10.1016/j.tcm.2017.07.010 28801207\n17. Banai S. Tzivoni D. Drug Therapy For Torsade de Pointes J. Cardiovasc. Electrophysiol. 1993 4 206 210 10.1111/j.1540-8167.1993.tb01224.x 8269292\n18. Al Khatib S.M. Stevenson W.G. Ackerman M.J. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society J. Am. Coll. Cardiol. 2018 72 e91 e220 29097296\n\n", "fulltext_license": "CC BY", "issn_linking": "2039-7275", "issue": "11(1)", "journal": "Clinics and practice", "keywords": "QT prolongation; Torsades de Pointes; drug-induced Torsades de Pointes; methadone; metoclopramide; metronidazole", "medline_ta": "Clin Pract", "mesh_terms": null, "nlm_unique_id": "101563282", "other_id": null, "pages": "101-105", "pmc": null, "pmid": "33562182", "pubdate": "2021-02-07", "publication_types": "D002363:Case Reports", "references": "28855066;16616034;26693921;30071529;14594906;26823389;29097296;20142454;8269292;11858397;19153406;15869686;14999113;19349637;28801207;26869865;14988369;15501692", "title": "Methadone, Metoclopramide and Metronidazole Interaction Causing Torsades de Pointes.", "title_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes" }

[ { "companynumb": "US-AMNEAL PHARMACEUTICALS-2021-AMRX-00776", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "071250", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE HYDROCHLORIDE IR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DIAMORPHINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HEROIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "071250", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE HYDROCHLORIDE IR" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "COCAINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "COCAINE" } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K., KARTHIK N., GERBER J.. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLIN. PRACT. 2021?11(1):101?05", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210309", "receivedate": "20210309", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18986677, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "US-UNICHEM PHARMACEUTICALS (USA) INC-UCM202103-000211", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "203458", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." } ], "patientagegroup": "5", "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLINICS AND PRACTICE. 2021 MAR 01?11(1):101?5. DOI:10.3390/CLINPRACT11010015", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20210311", "receivedate": "20210311", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19001357, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "US-CADILA HEALTHCARE LIMITED-US-ZYDUS-063272", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DIAMORPHINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HEROIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "206560", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "COCAINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "COCAINE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLINICS AND PRACTICE. 2021?11(1):101?105", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210325", "receivedate": "20210325", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19054428, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2021R1-287153", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "208305", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Electrocardiogram QT prolonged", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K.,KARTHIK N.,GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLIN PRACT. 2021?11:101?5", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210324", "receivedate": "20210324", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19052158, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "US-INNOGENIX, LLC-2108819", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": "3", "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "COCAINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "COCAINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "070772", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Long QT syndrome", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Unresponsive to stimuli", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLINICS AND PRACTICE 11: 101?105, NO. 1, 07 FEB 2021. HTTP://DOI.ORG/10.3390/CLINPRACT11010015.", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210402", "receivedate": "20210402", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 19085078, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210717" }, { "companynumb": "US-MYLANLABS-2021M1015356", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "INFUSED OVER 30 MIN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "021624", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "10 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Unresponsive to stimuli", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLINICS?PRACTICE 2021?11(1):101?105.", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210319", "receivedate": "20210319", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19032778, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210420" }, { "companynumb": "US-TOLMAR, INC.-21US025561", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "077264", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "VAGINAL GEL", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J.. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLIN PRACT. 2021?11(1):101?105", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210223", "receivedate": "20210223", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18930909, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "US-INFO-001185", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": null, "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SLOWLY INFUSED OVER 30 MINUTES", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLIN PRACT. 2021 FEB 7?11(1):101?105. DOI: 10.3390/CLINPRACT11010015. PMID: 33562182.", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210226", "receivedate": "20210226", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18943349, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "US-TEVA-2021-US-1893768", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "70184", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "70184", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": null, "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "INFUSED OVER 30 MIN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." } ], "patientagegroup": "5", "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Unresponsive to stimuli", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLINICS?PRACTICE 2021?11(1):101?105.", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210802", "receivedate": "20210328", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19066372, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" }, { "companynumb": "US-VISTAPHARM, INC.-VER202103-000866", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "040088", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "075051", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": "UNKNOWN (INFUSED OVER 30 MIN)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "075051", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DIAMORPHINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HEROIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "COCAINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "COCAINE" } ], "patientagegroup": "5", "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Confusional state", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLIN PRACT. 2021 FEB 07?11(1):101?5. DOI:10.3390/CLINPRACTL1010015", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20210330", "receivedate": "20210306", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18977552, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "US-B.BRAUN MEDICAL INC.-2108367", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "018900", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE INJECTION USP (5 MG/ML) IN PAB? PLASTIC CONTAINER (NDA 0" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, ET AL. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. J.CLIN. PRACT. 2021?11:101?105.", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210323", "receivedate": "20210323", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 19051000, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210420" }, { "companynumb": "US-BAXTER-2021BAX004473", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": null, "drugadministrationroute": "041", "drugauthorizationnumb": "018657", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INFUSION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE INJECTION, USP" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Long QT syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLINICS AND PRACTICE. 2021?11:101?105.", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210311", "receivedate": "20210311", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18996025, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "US-IPCA LABORATORIES LIMITED-IPC-2021-US-000738", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "78807", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "78807", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Electrocardiogram QT prolonged", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "KARTHIK GNANAPANDITHAN, NISHRUTHA KARTHIK AND JAIME GERBER.. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLIN. PRACT. 2021?11:101?105", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210327", "receivedate": "20210327", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19065485, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210420" }, { "companynumb": "US-STRIDES ARCOLAB LIMITED-2021SP003233", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG ABUSE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "070039", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, INFUSED OVER 30 MIN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J.. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLINICS?PRACTICE. 2021?11(1):101?105", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210317", "receivedate": "20210317", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19020701, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210420" }, { "companynumb": "US-EMCURE PHARMACEUTICALS LTD-2021-EPL-000540", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "204756", "drugbatchnumb": "UNK", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "10 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "204756", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": "UNK", "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": "INFUSION OVER 30 MIN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": "UNK", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Electrocardiogram QT prolonged", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J.. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLIN PRACT. 2021?11(1):101?105", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210225", "receivedate": "20210225", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18938031, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": null, "transmissiondate": "20210420" }, { "companynumb": "US-PFIZER INC-2021207066", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "073118", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE HCL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DIAMORPHINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HEROIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "073118", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE HCL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "COCAINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "COCAINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "020868", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "MODIFIED-RELEASE TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN, K.. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLINICS AND PRACTICE. 2021?11(1):101?105", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210304", "receivedate": "20210304", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18969803, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": 1, "seriousnessother": null, "transmissiondate": "20210420" }, { "companynumb": "US-FRESENIUS KABI-FK202102486", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "091392", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE INJECTION, USP" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE (MANUFACTURER UNKNOWN)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "UNSPECIFIED INGREDIENT" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NO DRUG NAME" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "COCAINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "COCAINE" } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLINICS AND PRACTICE. 2021 MAR?11 (1):101?105.", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210315", "receivedate": "20210315", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19010953, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": 1, "seriousnessother": null, "transmissiondate": "20210420" }, { "companynumb": "US-HIKMA PHARMACEUTICALS USA INC.-US-H14001-21-53881", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "METRONIDAZOLE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METRONIDAZOLE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA ASPIRATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHADONE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "006134", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG DEPENDENCE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHADONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NAUSEA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Torsade de pointes", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Long QT syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "GNANAPANDITHAN K, KARTHIK N, GERBER J. METHADONE, METOCLOPRAMIDE AND METRONIDAZOLE INTERACTION CAUSING TORSADES DE POINTES. CLINICS AND PRACTICE. 2021?11(1):101?05. DOI:10.3390/CLINPRACT11010015.", "literaturereference_normalized": "methadone metoclopramide and metronidazole interaction causing torsades de pointes", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20210318", "receivedate": "20210318", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19023583, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20210420" } ]

{ "abstract": "Central retinal artery occlusion (CRAO) is uncommon among children and young adults. Bilateral CRAO before the age of 18 years are extremely rare. We present a case of an idiopathic bilateral CRAO in a young healthy female.", "affiliations": "Northwestern University Feinberg School of Medicine and the Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.;Northwestern University Feinberg School of Medicine and the Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.;Northwestern University Feinberg School of Medicine and the Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.;Northwestern University Feinberg School of Medicine and the Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.;Northwestern University Feinberg School of Medicine and the Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.;Northwestern University Feinberg School of Medicine and the Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois. Electronic address: jlaskyzeid@luriechildrens.org.", "authors": "Kinori|Michael|M|;Simon|Shira S|SS|;Kurup|Sudhi P|SP|;Mets-Halgrimson|Rebecca|R|;Jampol|Lee M|LM|;Zeid|Janice Lasky|JL|", "chemical_list": "D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D005938:Glucocorticoids; D010959:Tissue Plasminogen Activator; D009173:Mycophenolic Acid; D008775:Methylprednisolone", "country": "United States", "delete": false, "doi": "10.1016/j.jaapos.2017.04.013", "fulltext": null, "fulltext_license": null, "issn_linking": "1091-8531", "issue": "21(5)", "journal": "Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus", "keywords": null, "medline_ta": "J AAPOS", "mesh_terms": "D000293:Adolescent; D001766:Blindness; D004791:Enzyme Inhibitors; D005260:Female; D005343:Fibrinolytic Agents; D005451:Fluorescein Angiography; D005938:Glucocorticoids; D006801:Humans; D008279:Magnetic Resonance Imaging; D008775:Methylprednisolone; D009173:Mycophenolic Acid; D015356:Retinal Artery Occlusion; D010959:Tissue Plasminogen Activator; D041623:Tomography, Optical Coherence; D015354:Vision, Low; D014792:Visual Acuity", "nlm_unique_id": "9710011", "other_id": null, "pages": "418-420.e1", "pmc": null, "pmid": "28844751", "pubdate": "2017-10", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Idiopathic bilateral central artery occlusion in a young woman.", "title_normalized": "idiopathic bilateral central artery occlusion in a young woman" }

[ { "companynumb": "US-ROCHE-2140504", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "ALTEPLASE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "103172", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ATRIAL FIBRILLATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACTILYSE" } ], "patientagegroup": null, "patientonsetage": "15", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "No adverse event", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "KINORI M, SIMON S, KURUP S, METS-HALGRIMSON R, JAMPOL L, ZEID J, ET AL IDIOPATHIC BILATERAL CENTRAL ARTERY OCCLUSION IN A YOUNG WOMAN. JOURNAL OF AAPOS 2017?21(5):418-420.", "literaturereference_normalized": "idiopathic bilateral central artery occlusion in a young woman", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181205", "receivedate": "20181205", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15687904, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190205" } ]

{ "abstract": "BACKGROUND\nGastric cancer is the fifth most diagnosed cancer worldwide and the third most common cause of cancer-related death. In recent decades, increasing application of next-generation sequencing has enabled detection of molecular aberrations, including fusions. In cases where tissue is difficult to obtain, cell-free DNA (cfDNA) is used for detecting mutations to identify the molecular profile of cancer. Here, we report a rare case of EGFR-SEPT14 fusion detected from cfDNA analysis in a patient with gastric cancer.\n\n\nMETHODS\nA 49-year-old female diagnosed with advanced gastric cancer in July 2019 received capecitabine and then combination chemotherapy of ramucirumab and paclitaxel, but ascites was detected. The therapy was switched to nivolumab, but disease progression was observed on a positron emission tomography/computed tomography scan in May 2020. Therapy was discontinued, and cfDNA next-generation sequencing was immediately evaluated. All genomic variants, including fusions, were analyzed from cfDNA. The following somatic alterations were detected from the patient's cfDNA: an APC frameshift mutation (NM_000038.5:c.6579del, p.V2194fs) with variant allele frequency of 0.5%, an EGFR amplification with a copy number of 17.3, and an EGFR-SEPT14 fusion with variant allele frequency of 45.3%. The site of the fusion was exon 24 of EGFR fused to exon 10 of SEPT14. The fusion was in-frame and considered to be protooncogenic. Although the patient refused to continue therapy, we suggest that EGFR-targeted therapies be tried in such future cases.\n\n\nCONCLUSIONS\nThe expanded applications of the cfDNA assay may open a new horizon in treatment of patients with advanced gastric cancer.", "affiliations": "Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea.;Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea.;Center for Precision Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea.;Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea.;Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea. kal1119@yuhs.ac.", "authors": "Kim|Boyeon|B|;Kim|Yoonjung|Y|;Park|Inho|I|;Cho|Jae Yong|JY|;Lee|Kyung-A|KA|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.12998/wjcc.v9.i12.2884", "fulltext": "\n==== Front\nWorld J Clin Cases\nWJCC\nWorld Journal of Clinical Cases\n2307-8960\nBaishideng Publishing Group Inc\n\njWJCC.v9.i12.pg2884\n10.12998/wjcc.v9.i12.2884\nCase Report\nDetection of EGFR-SEPT14 fusion in cell-free DNA of a patient with advanced gastric cancer: A case report\nKim B et al. EGFR-SEPT14 fusion in advanced gastric cancer\nKim Boyeon Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea\nDepartment of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea\n\nKim Yoonjung Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea\n\nPark Inho Center for Precision Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea\n\nCho Jae Yong Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea\n\nLee Kyung-A Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea. kal1119@yuhs.ac\n\nAuthor contributions: Kim B reviewed the literature and contributed to manuscript drafting; Cho JY provided clinical information regarding the patient; Kim Y and Park I contributed to panel assay design and gene curation; Kim B, Kim Y, and Lee KA performed analysis of genetic data; Lee KA and Cho JY were responsible for revision of the manuscript for important intellectual content; All authors issued final approval for the version to be submitted.\n\nCorresponding author: Kyung-A Lee, MD, PhD, Full Professor, Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-Ro, Gangnam-Gu, Seoul 06273, South Korea. kal1119@yuhs.ac\n\n26 4 2021\n26 4 2021\n9 12 28842889\n4 12 2020\n2 2 2021\n3 3 2021\n©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.\n2021\nhttps://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.\nBACKGROUND\n\nGastric cancer is the fifth most diagnosed cancer worldwide and the third most common cause of cancer-related death. In recent decades, increasing application of next-generation sequencing has enabled detection of molecular aberrations, including fusions. In cases where tissue is difficult to obtain, cell-free DNA (cfDNA) is used for detecting mutations to identify the molecular profile of cancer. Here, we report a rare case of EGFR-SEPT14 fusion detected from cfDNA analysis in a patient with gastric cancer.\n\nCASE SUMMARY\n\nA 49-year-old female diagnosed with advanced gastric cancer in July 2019 received capecitabine and then combination chemotherapy of ramucirumab and paclitaxel, but ascites was detected. The therapy was switched to nivolumab, but disease progression was observed on a positron emission tomography/computed tomography scan in May 2020. Therapy was discontinued, and cfDNA next-generation sequencing was immediately evaluated. All genomic variants, including fusions, were analyzed from cfDNA. The following somatic alterations were detected from the patient’s cfDNA: an APC frameshift mutation (NM_000038.5:c.6579del, p.V2194fs) with variant allele frequency of 0.5%, an EGFR amplification with a copy number of 17.3, and an EGFR-SEPT14 fusion with variant allele frequency of 45.3%. The site of the fusion was exon 24 of EGFR fused to exon 10 of SEPT14. The fusion was in-frame and considered to be protooncogenic. Although the patient refused to continue therapy, we suggest that EGFR-targeted therapies be tried in such future cases.\n\nCONCLUSION\n\nThe expanded applications of the cfDNA assay may open a new horizon in treatment of patients with advanced gastric cancer.\n\nGene fusion\nCell-free DNA\nLiquid biopsy\nGastric cancer\nEGFR tyrosine kinase inhibitor\nCase report\n==== Body\nCore Tip: In recent decades, increasing application of next-generation sequencing has enabled detection of molecular aberrations, including fusions. In cases where tissue is not easily obtainable, cell-free DNA is used for detecting mutations to determine the molecular profile of cancer. In this study, we report the first case of EGFR-SEPT14 fusion detected from next-generation sequencing analysis of cell-free DNA from a patient with advanced gastric cancer. We suggest expanded applications of the cell-free DNA assay regardless of cancer type, which may open a new horizon in treatment of patients with advanced gastric cancer.\n\nINTRODUCTION\n\nGastric cancer is the fifth most diagnosed cancer worldwide with a particularly high incidence in East Asia and the third most common cause of cancer-related death[1]. Curative surgery is the primary treatment of choice, but systemic chemotherapies are used for patients with metastatic or unresectable advanced or recurrent gastric cancer. Because systemic chemotherapies are nonspecific and can cause serious adverse effects, development of molecular targeted drugs has been attempted to improve outcomes in patients with gastric cancer.\n\nIn recent decades, increasing application of next-generation sequencing (NGS) has enabled detection of molecular aberrations such as copy number gains or losses, somatic mutations, and gene fusions. For cases where tissue is not easily obtainable, cell-free DNA (cfDNA) is used for detecting mutations to determine the molecular profile of cancer[2]. Successful identification of oncogenic gene fusions can aid in diagnosis and molecular treatment of patients[3]. Here, we report a rare case of EGFR-SEPT14 fusion detected from cfDNA analysis in a patient with gastric cancer.\n\nCASE PRESENTATION\n\nChief complaints\n\nA 49-year-old female patient had been treated for advanced gastric cancer (AGC) with chemotherapy. After therapy, she expressed whole body pain, especially on the left side of the pelvis.\n\nHistory of present illness\n\nThis patient had been diagnosed with AGC in July 2019. The pathological diagnosis indicated signet ring cell carcinoma. While receiving her first round of chemotherapy with capecitabine, the patient developed acute pyelonephritis and hydronephrosis in both kidneys, leading to a suspicion of periureteral metastases. Therefore, the patient started a new regimen of combination chemotherapy with ramucirumab and paclitaxel. However, ascites was observed after two cycles of chemotherapy. The treatment was switched to nivolumab. After five cycles, an abdominopelvic computed tomography scan was performed in April 2020 that showed improvement in peritoneal carcinomatosis compared to an image from February 2020. She received seven cycles of nivolumab, but progressive disease was observed by the positron emission tomography/computed tomography scan, and other therapeutic options were needed to be discussed.\n\nHistory of past illness\n\nThe patient did not have any other medical history beyond AGC.\n\nPersonal and family history\n\nThe patient reported a family history of gastric cancer in her grandfather.\n\nPhysical examination\n\nPhysical examination revealed pain on the left side of the pelvis.\n\nLaboratory examinations\n\nBlood analysis revealed mild leukocytosis (14 × 109/L) with low hemoglobin (10.3 g/dL). Platelet count was in the normal range. Serum C-reactive protein was increased at 181 mg/L (normal range, 0.1-6.0 mg/L).\n\nImaging examinations\n\nA positron emission tomography/computed tomography scan obtained in May 2020 revealed bone, multiple nodal, and right lateral abdominal wall soft tissue metastases after the patient had received seven cycles of nivolumab. The therapy was discontinued, and cfDNA NGS was performed immediately.\n\nFurther genetic diagnostic work-up\n\nFor genetic testing, the patient provided informed written consent for specimen collection and genetic analysis. This study was approved with a waiver of informed consent by the Institutional Review Board of Gangnam Severance Hospital, Seoul, Korea (IRB No. 3-2020-0268).\n\ncfDNA was extracted using the MagMAX Cell-Free Total Nucleic Acid Kit (Thermo Fisher Scientific, Waltham, MA, United States). A DNA library was constructed with the AlphaLiquid®100 kit (IMBDx Inc., Seoul, Korea), which was designed to include intronic regions of target genes. Hybrid-capture-selected libraries were sequenced to a mean coverage of 14237x (cfDNA) and 735x (DNA) on an Illumina NextSeq-550 (Illumina, San Diego, CA, United States). GeneFuse was used to detect fusions[4], and a Genome Reference Consortium Human Build 38 was used for variant interpretation. All genomic variants, including fusions, were analyzed from cfDNA. Because of the patient’s family history, the presence of germline mutation was tested in parallel for the following genes: APC, ATM, BRCA1, BRCA2, CDH1, CDK4, CDKN2A, and MLH1. No germline mutations were detected from the genomic DNA. Somatic alterations detected from the cfDNA were an APC frameshift mutation (NM_000038.5:c.6579del, p.V2194fs) with variant allele frequency of 0.5%, an EGFR amplification with a copy number of 17.3, and an EGFR-SEPT14 fusion with variant allele frequency of 45.3% (Figure 1A). Because the EGFR and SEPT14 genes are closely located on chromosome 7, we tested 50 normal healthy controls with the same panel and confirmed that the fusion detected in the patient was a true positive. We also confirmed EGFR-SEPT14 fusion by complementary DNA sequencing, which was processed using the patient’s cell-free RNA extracted by MagMAX Cell-Free Total Nucleic Acid Kit. The site of fusion was exon 24 of EGFR fused to exon 10 of SEPT14 (Figure 1B). The fusion was in-frame and considered to be proto-oncogenic.\n\nFigure 1 EGFR-SEPT14 fusion. A: Genomic fusion of EGFR exon 24 with exon 10 of SEPT14; B: RNA sequencing analysis of the EGFR-SEPT14 fusion.\n\nFINAL DIAGNOSIS\n\nThe final diagnosis of the present case was EGFR-SEPT14 fusion in AGC.\n\nTREATMENT\n\nThe patient refused further treatment.\n\nOUTCOME AND FOLLOW-UP\n\nThe patient could have tried EGFR targeted therapy such as erlotinib, which has been used in other types of carcinomas with EGFR-SEPT14 fusion[5], but she refused further treatment and passed away about 1 month after discontinuation of nivolumab.\n\nDISCUSSION\n\nEGFR1 (EGFR; ErbB1; HER1) is one of four transmembrane growth factor receptor proteins that constitute the EGFR family of receptor tyrosine kinases[6]. Activation of EGFR leads to cell proliferation, differentiation, motility, and metastasis[7]. SEPT14 is a member of a highly conserved septin family of guanosine 5’-triphosphate-binding cytoskeletal proteins with multiple cellular functions, such as membrane transport, apoptosis, cell polarity, cell cycle regulation, cytokinesis, and oncogenesis[8]. Among all septins, SEPT14 shows the highest mutation frequency in skin cancer followed by SEPT9 exhibiting high mutation frequency in stomach cancer[9].\n\nThe EGFR-SEPT14 fusion was first reported in glioblastoma in which the site of fusion was the tyrosine kinase domain of EGFR and the coiled-coil domain of SEPT14. The EGFR-SEPT14 fusion is the most frequent functional gene fusion in human glioblastoma[10]. The EGFR-SEPT14 fusion was also identified in tissue from salivary gland secretory carcinoma using fluorescence in situ hybridization. That previous case indicated that a tumor harboring this fusion would be sensitive to EGFR inhibitors[11]. Recently, the EGFR-SEPT14 fusion was reported in colorectal adenocarcinoma by using a comprehensive NGS assay on tumor samples[5].\n\nIn the present study, the tissue biopsy of the patient was difficult. Therefore, we used a comprehensive NGS assay with a sample of cfDNA from the patient. We identified an EGFR-SEPT14 fusion in AGC. To our knowledge, this is the first case of EGFR-SEPT14 fusion identified in a cfDNA sample from an AGC patient. The patient went through unusually rapid disease progression, and this progression might have been caused by the fusion mutation. Unfortunately, because the patient refused to continue therapy, we could not determine whether the EGFR-SEPT14 fusion responded to EGFR targeted therapies, such as tyrosine kinase inhibitors. However, the use of such therapies might have been effective in AGC with an EGFR-SEPT14 fusion because there was a report of a patient with colorectal cancer with an EGFR-SEPT14 fusion treated with erlotinib therapy. The fusion site reported in that study is the same as that in the present study, and the patient was administered erlotinib therapy to which the EGFR-SEPT14 fusion is known to be sensitive[10]. However, soon after treatment, an EGFR variant III was detected and can result in resistance to erlotinib[5]. To confirm the treatment effect and disease progression in AGC, further studies are needed.\n\nNevertheless, detection of genomic fusion by the well-established cfDNA NGS assay confirmed that cfDNA can serve as an alternate source for detecting gene aberrations, including fusions. Furthermore, EGFR-SEPT14 fusion has been reported in various types of cancer. Therefore, expanded applications of cfDNA assays should be considered regardless of cancer type. We also suggest that genomic variants including fusions can be therapeutic targets in AGC, which may open a new horizon in treatment.\n\nCONCLUSION\n\nTo the best of our knowledge, this is the first case of an EGFR-SEPT14 fusion identified in a cfDNA sample from a patient with AGC. Detection of genomic fusion by the well-established cfDNA NGS assay confirmed that cfDNA can serve as an alternate source for detecting gene aberrations, including fusions. Successful identification of genomic variants, including fusions, from cfDNA can aid in diagnosis and molecular treatment of patients with AGC.\n\nInformed consent statement: Informed written consent was obtained for specimen collection and genetic analysis.\n\nConflict-of-interest statement: The authors declare that they have no conflict of interest.\n\nCARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).\n\nManuscript source: Unsolicited manuscript\n\nPeer-review started: December 4, 2020\n\nFirst decision: January 24, 2021\n\nArticle in press: March 3, 2021\n\nSpecialty type: Medicine, research and experimental\n\nCountry/Territory of origin: South Korea\n\nPeer-review report’s scientific quality classification\n\nGrade A (Excellent): 0\n\nGrade B (Very good): B\n\nGrade C (Good): 0\n\nGrade D (Fair): 0\n\nGrade E (Poor): 0\n\nP-Reviewer: Jin X S-Editor: Fan JR L-Editor: Filipodia P-Editor: Yuan YY\n==== Refs\n1 Bray F Ferlay J Soerjomataram I Siegel RL Torre LA Jemal A Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA Cancer J Clin 2018 68 394 424 30207593\n2 Volckmar AL Sültmann H Riediger A Fioretos T Schirmacher P Endris V Stenzinger A Dietz S A field guide for cancer diagnostics using cell-free DNA: From principles to practice and clinical applications Genes Chromosomes Cancer 2018 57 123 139 29205637\n3 Schram AM Chang MT Jonsson P Drilon A Fusions in solid tumours: diagnostic strategies, targeted therapy, and acquired resistance Nat Rev Clin Oncol 2017 14 735 748 28857077\n4 Chen S Liu M Huang T Liao W Xu M Gu J GeneFuse: detection and visualization of target gene fusions from DNA sequencing data Int J Biol Sci 2018 14 843 848 29989075\n5 Li Y Zhang HB Chen X Yang X Ye Y Bekaii-Saab T Zheng Y Zhang Y A Rare EGFR-SEPT14 Fusion in a Patient with Colorectal Adenocarcinoma Responding to Erlotinib Oncologist 2020 25 203 207 32162810\n6 Herbst RS Review of epidermal growth factor receptor biology Int J Radiat Oncol Biol Phys 2004 59 21 26\n7 Sigismund S Avanzato D Lanzetti L Emerging functions of the EGFR in cancer Mol Oncol 2018 12 3 20 29124875\n8 Peterson EA Kalikin LM Steels JD Estey MP Trimble WS Petty EM Characterization of a SEPT9 interacting protein, SEPT14, a novel testis-specific septin Mamm Genome 2007 18 796 807 17922164\n9 Angelis D Spiliotis ET Septin Mutations in Human Cancers Front Cell Dev Biol 2016 4 122 27882315\n10 Frattini V Trifonov V Chan JM Castano A Lia M Abate F Keir ST Ji AX Zoppoli P Niola F Danussi C Dolgalev I Porrati P Pellegatta S Heguy A Gupta G Pisapia DJ Canoll P Bruce JN McLendon RE Yan H Aldape K Finocchiaro G Mikkelsen T Privé GG Bigner DD Lasorella A Rabadan R Iavarone A The integrated landscape of driver genomic alterations in glioblastoma Nat Genet 2013 45 1141 1149 23917401\n11 Black M Liu CZ Onozato M Iafrate AJ Darvishian F Jour G Cotzia P Concurrent Identification of Novel EGFR-SEPT14 Fusion and ETV6-RET Fusion in Secretory Carcinoma of the Salivary Gland Head Neck Pathol 2020 14 817 821 31502214\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "2307-8960", "issue": "9(12)", "journal": "World journal of clinical cases", "keywords": "Case report; Cell-free DNA; EGFR tyrosine kinase inhibitor; Gastric cancer; Gene fusion; Liquid biopsy", "medline_ta": "World J Clin Cases", "mesh_terms": null, "nlm_unique_id": "101618806", "other_id": null, "pages": "2884-2889", "pmc": null, "pmid": "33969073", "pubdate": "2021-04-26", "publication_types": "D002363:Case Reports", "references": "29989075;23917401;31502214;29205637;17922164;29124875;30207593;27882315;28857077;15142631;32162810", "title": "Detection of EGFR-SEPT14 fusion in cell-free DNA of a patient with advanced gastric cancer: A case report.", "title_normalized": "detection of egfr sept14 fusion in cell free dna of a patient with advanced gastric cancer a case report" }

[ { "companynumb": "KR-PFIZER INC-202100968358", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "RAMUCIRUMAB" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, CYCLIC (TWO CYCLES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "GASTRIC CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RAMUCIRUMAB" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "076131", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, CYCLIC (TWO CYCLES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "GASTRIC CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL." } ], "patientagegroup": null, "patientonsetage": "49", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Ascites", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "KIM, B.. DETECTION OF EGFR?SEPT14 FUSION IN CELL?FREE DNA OF A PATIENT WITH ADVANCED GASTRIC CANCER: A CASE REPORT. WORLD JOURNAL OF CLINICAL CASES. 2021?9 (12):2884?2889", "literaturereference_normalized": "detection of egfr sept14 fusion in cell free dna of a patient with advanced gastric cancer a case report", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20210812", "receivedate": "20210812", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19691886, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" } ]

{ "abstract": "Nivolumab, an anti-PD-1 antibody, is now considered an important therapeutic agent in several advanced malignancies. However, immune-related adverse events such as endocrinopathies have been reported with its use. Thyroid disorder and isolated adrenocorticotropic hormone deficiency have frequently been reported as nivolumab-induced immune-related adverse events. Another endocrinopathy is nivolumab-induced type 1 diabetes mellitus (t1dm), described as diabetes mellitus with rapid onset and complete insulin insufficiency, at times leading to fulminant t1dm. We report the case of a 68-year-old woman who developed pancreatic islet-related autoantibody-negative t1dm, possibly induced by nivolumab, under continuous glucocorticoid administration. She was treated with nivolumab for advanced malignant melanoma, concomitant with 10 mg prednisolone daily for thrombophlebitis tapered to 5 mg after 13 courses of nivolumab therapy. At approximately the 27th course of nivolumab therapy, she showed elevated plasma glucose levels despite preserved insulin secretion. A month later, she developed diabetic ketoacidosis. Her insulin secretion decreased and finally was exhausted. She was diagnosed with acute-onset rather than fulminant t1dm because of a rapidly progressive course to diabetic ketoacidosis during just more than 1 week. She is currently receiving insulin replacement. There has been no recurrence of the melanoma. Thus, nivolumab might induce autoimmune diabetes mellitus, with patients having t1dm-sensitive human leucocyte antigen being more susceptible even when receiving glucocorticoids. Physicians should be aware that nivolumab could potentially induce t1dm as a critical immune-related adverse event.", "affiliations": "Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.;Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.;Department of Dermatology, Kyushu University Hospital, Fukuoka City, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.;Department of Dermatology, Kyushu University Hospital, Fukuoka City, Japan.;Department of Dermatology, Kyushu University Hospital, Fukuoka City, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.;Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Japan.", "authors": "Sakaguchi|C|C|;Ashida|K|K|;Yano|S|S|;Ohe|K|K|;Wada|N|N|;Hasuzawa|N|N|;Matsuda|Y|Y|;Sakamoto|S|S|;Sakamoto|R|R|;Uchi|H|H|;Furue|M|M|;Nomura|M|M|;Ogawa|Y|Y|", "chemical_list": "D000077594:Nivolumab", "country": "Switzerland", "delete": false, "doi": "10.3747/co.26.4130", "fulltext": null, "fulltext_license": null, "issn_linking": "1198-0052", "issue": "26(1)", "journal": "Current oncology (Toronto, Ont.)", "keywords": "Melanoma; adverse drug events; autoimmunity; diabetes mellitus; nivolumab; type 1 diabetes", "medline_ta": "Curr Oncol", "mesh_terms": "D000368:Aged; D003922:Diabetes Mellitus, Type 1; D005260:Female; D006801:Humans; D008545:Melanoma; D000077594:Nivolumab", "nlm_unique_id": "9502503", "other_id": null, "pages": "e115-e118", "pmc": null, "pmid": "30853818", "pubdate": "2019-02", "publication_types": "D002363:Case Reports", "references": "27297738;27696192;28848559;29254501;28689073;27761609;27181090;25805871;28031819;11777359;28418115;28255845;27881588;28785924;19812988;27141885;22658127;1644920;28068177;28877632;24843620;28017788;29098805;17653640;326604", "title": "A case of nivolumab-induced acute-onset type 1 diabetes mellitus in melanoma.", "title_normalized": "a case of nivolumab induced acute onset type 1 diabetes mellitus in melanoma" }

[ { "companynumb": "JP-BAUSCH-BL-2020-007786", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "75250", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNKNOWN DATE IN SEPTEMBER IT WAS DISCONTINUED", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "40069", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "POTASSIUM IODIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "INCREASED THE DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "POTASSIUM IODIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NIVOLUMAB" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNKNOWN DATE IN APRIL", "drugenddate": null, "drugenddateformat": null, "drugindication": "VAGINAL CANCER RECURRENT", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NIVOLUMAB" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "75250", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNKNOWN DATE IN APRIL", "drugenddate": null, "drugenddateformat": null, "drugindication": "THROMBOPHLEBITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "POTASSIUM IODIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "BASEDOW^S DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "POTASSIUM IODIDE." } ], "patientagegroup": null, "patientonsetage": "68", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug resistance", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Adrenal insufficiency", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SAKAGUCHI C, ASHIDA K, YANO S, OHE K, WADA N, HASUZAWA N, MATSUDA Y, SAKAMOTO S, SAKAMOTO R, UCHI H, FURUE M, NOMURA M, OGAWA Y. A CASE OF NIVOLUMAB-INDUCED ACUTE-ONSET TYPE 1 DIABETES MELLITUS IN MELANOMA. CURRENT ONCOLOGY. 2019 FEB?26 (1):E115-E118. DOI:HTTPS://DOI.ORG/10.3747/CO.26.4130", "literaturereference_normalized": "a case of nivolumab induced acute onset type 1 diabetes mellitus in melanoma", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20200319", "receivedate": "20200319", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17562307, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200409" }, { "companynumb": "JP-TEVA-2020-JP-1203611", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "080354", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM DAILY; INITIAL DOSE; TAPERED TO 5MG DAILY AFTER 1 WEEK", "drugenddate": null, "drugenddateformat": null, "drugindication": "THROMBOPHLEBITIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "3", "activesubstance": { "activesubstancename": "POTASSIUM IODIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "BASEDOW^S DISEASE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "POTASSIUM IODIDE." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "080354", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "THROMBOPHLEBITIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NIVOLUMAB" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "MALIGNANT MELANOMA", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NIVOLUMAB" } ], "patientagegroup": null, "patientonsetage": "68", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Adrenal insufficiency", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperthyroidism", "reactionmeddraversionpt": "22.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Type 1 diabetes mellitus", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SAKAGUCHI C, ASHIDA K, YANO S, OHE K, WADA N, HASUZAWA N, ET AL. A CASE OF NIVOLUMAB-INDUCED ACUTE-ONSET TYPE 1 DIABETES MELLITUS IN MELANOMA. CURR-ONCOL 2019?26(1):E115-E118.", "literaturereference_normalized": "a case of nivolumab induced acute onset type 1 diabetes mellitus in melanoma", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20200318", "receivedate": "20200318", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17553597, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200409" } ]

{ "abstract": "Tumor lysis syndrome (TLS) is an oncologic emergency characterized by spillage of intracellular material into the blood caused by disruption of massive load of tumor cells. It is more commonly reported in hematological cancers and can have fatal consequences due to renal and multi-organ failure and arrhythmias due to electrolyte imbalance. We describe a case with metastatic breast cancer who presented with TLS after a single dose of paclitaxel, second such case in literature. The development of a risk stratification score to assess the need for hospitalization or close observation of these patients and the documentation of appropriate preventive strategies could help prevent such fatal occurrences. TLS should be included in the differential when cancer patients on treatment present with acute decompensation.", "affiliations": "Department of Internal Medicine, SUNY Upstate Medical University, Syracuse, NY. Electronic address: gaurang2489@gmail.com.;Department of Critical Care, Crouse Hospital, Syracuse, NY.", "authors": "Vaidya|Gaurang Nandkishor|GN|;Acevedo|Russell|R|", "chemical_list": "D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel", "country": "United States", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0735-6757", "issue": "33(2)", "journal": "The American journal of emergency medicine", "keywords": null, "medline_ta": "Am J Emerg Med", "mesh_terms": "D000972:Antineoplastic Agents, Phytogenic; D001943:Breast Neoplasms; D018270:Carcinoma, Ductal, Breast; D005260:Female; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel; D014057:Tomography, X-Ray Computed; D015275:Tumor Lysis Syndrome", "nlm_unique_id": "8309942", "other_id": null, "pages": "308.e1-2", "pmc": null, "pmid": "25178848", "pubdate": "2015-02", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Tumor lysis syndrome in metastatic breast cancer after a single dose of paclitaxel.", "title_normalized": "tumor lysis syndrome in metastatic breast cancer after a single dose of paclitaxel" }

[ { "companynumb": "US-ACTAVIS-2015-10754", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ANASTROZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HORMONE THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANASTROZOLE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "090130", "drugbatchnumb": "UNCONFIRMED", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNK", "drugdosagetext": "80 MG/M2, SINGLE", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "80", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL (ATLLC)" } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tumour lysis syndrome", "reactionmeddraversionpt": "18.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "VAIDYA GN, ACEVEDO R. TUMOR LYSIS SYNDROME IN METASTATIC BREAST CANCER AFTER A SINGLE DOSE OF PACLITAXEL. AM J EMERG MED. 2015;33(2):308.E1-2", "literaturereference_normalized": "tumor lysis syndrome in metastatic breast cancer after a single dose of paclitaxel", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150605", "receivedate": "20150605", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11168667, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150821" }, { "companynumb": "US-ACCORD-025948", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "075436", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SINGLE WEEKLY DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "80", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL/PACLITAXEL LIPOSOME" } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Metabolic encephalopathy", "reactionmeddraversionpt": "17.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Cardiopulmonary failure", "reactionmeddraversionpt": "17.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Renal failure acute", "reactionmeddraversionpt": "17.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Tumour lysis syndrome", "reactionmeddraversionpt": "17.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Haemodialysis", "reactionmeddraversionpt": "17.1", "reactionoutcome": null }, { "reactionmeddrapt": "Liver injury", "reactionmeddraversionpt": "17.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Rhabdomyolysis", "reactionmeddraversionpt": "17.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "VAIDYA GN, ACEVEDO R. TUMOR LYSIS SYNDROME IN METASTATIC BREAST CANCER AFTER A SINGLE DOSE OF PACLITAXEL. AM J EMERG MED. 2014 AUG 7.", "literaturereference_normalized": "tumor lysis syndrome in metastatic breast cancer after a single dose of paclitaxel", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20140920", "receivedate": "20140920", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10465529, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150326" }, { "companynumb": "PHHY2015US040601", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "ANASTROZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANASTROZOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "078167", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "80 MG/M2, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "80", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL." } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hyperkalaemia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Rhabdomyolysis", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Liver injury", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Blood lactate dehydrogenase increased", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Blood uric acid increased", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Confusional state", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypotension", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Metabolic encephalopathy", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Sluggishness", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Somnolence", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperphosphataemia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hepatic enzyme increased", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Oliguria", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypercapnia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperuricaemia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Renal impairment", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cardiopulmonary failure", "reactionmeddraversionpt": "18.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Tumour lysis syndrome", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bradypnoea", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Electrolyte imbalance", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dyspnoea", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "VAIDYA GN, ACEVEDO R.. TUMOR LYSIS SYNDROME IN METASTATIC BREAST CANCER AFTER A SINGLE DOSE OF PACLITAXEL. AM-J-EMERG-MED. 2015;33(2):308.E1-308.E2", "literaturereference_normalized": "tumor lysis syndrome in metastatic breast cancer after a single dose of paclitaxel", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150414", "receivedate": "20150414", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11025422, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150821" }, { "companynumb": "US-MYLANLABS-2015M1012149", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "091540", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SINGLE DOSE 80 MG/M2 WEEKLY", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ANASTROZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANASTROZOLE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cardiopulmonary failure", "reactionmeddraversionpt": "18.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Tumour lysis syndrome", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "VAIDYA GN, ACEVEDO R. TUMOR LYSIS SYNDROME IN METASTATIC BREAST CANCER AFTER A SINGLE DOSE OF PACLITAXEL. AM-J-EMERG-MED 2015; 33(2):308E1-308E2.", "literaturereference_normalized": "tumor lysis syndrome in metastatic breast cancer after a single dose of paclitaxel", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150414", "receivedate": "20150414", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11026590, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150821" }, { "companynumb": "US-TEVA-555474USA", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ANASTROZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANASTROZOLE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "075297", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SINGLE DOSE 80 MG/M2 WEEKLY", "drugenddate": null, "drugenddateformat": null, "drugindication": "BREAST CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL." } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tumour lysis syndrome", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "VAIDYA GN, ACEVEDO R. TUMOR LYSIS SYNDROME IN METASTATIC BREAST CANCER AFTER A SINGLE DOSE OF PACLITAXEL. AM-J-EMERG-MED 2015; 33(2):308E1-308E2.", "literaturereference_normalized": "tumor lysis syndrome in metastatic breast cancer after a single dose of paclitaxel", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150420", "receivedate": "20150420", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11048961, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150821" } ]

{ "abstract": "Levetiracetam is a novel antiepileptic drug with an unknown mechanism of action. To-date levetiracetam is not known to be associated with any clinically significant pharmacokinetic interaction. Similarly, levetiracetam has not been associated with any pharmacodynamic interactions. We present four patients with severe refractory epilepsy in whom introduction of levetiracetam led to disabling symptoms compatible with carbamazepine toxicity requiring either carbamazepine dose reduction or levetiracetam withdrawal. As carbamazepine and carbamazepine-epoxide blood levels were not altered during levetiracetam co-medication, a pharmacodynamic interaction is suggested. Therefore, during levetiracetam co-medication with carbamazepine, patients should be monitored closely for symptoms of carbamazepine toxicity.", "affiliations": "Pharmacology and Therapeutics Unit, Department of Clinical and Experimental Epilepsy, University College London, UK.", "authors": "Sisodiya|Sanjay M|SM|;Sander|Josemir W A S|JW|;Patsalos|Philip N|PN|", "chemical_list": "D000927:Anticonvulsants; D002220:Carbamazepine; D000077287:Levetiracetam; D010889:Piracetam", "country": "Netherlands", "delete": false, "doi": "10.1016/s0920-1211(01)00309-6", "fulltext": null, "fulltext_license": null, "issn_linking": "0920-1211", "issue": "48(3)", "journal": "Epilepsy research", "keywords": null, "medline_ta": "Epilepsy Res", "mesh_terms": "D000328:Adult; D000927:Anticonvulsants; D002220:Carbamazepine; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010889:Piracetam", "nlm_unique_id": "8703089", "other_id": null, "pages": "217-9", "pmc": null, "pmid": "11904240", "pubdate": "2002-02", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Carbamazepine toxicity during combination therapy with levetiracetam: a pharmacodynamic interaction.", "title_normalized": "carbamazepine toxicity during combination therapy with levetiracetam a pharmacodynamic interaction" }

[ { "companynumb": "GB-MYLANLABS-2007S1013672", "fulfillexpeditecriteria": "1", "occurcountry": "GB", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "PRIMIDONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MG (NOCTE)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRIMIDONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "600 MG, 2X/DAY (CONTROL?RELEASE)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "076919", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "076919", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.5 MG NOCTE", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.5 MG MANE", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4 MG,QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "4", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MG MIDI", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "076919", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG,BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "600 MG,QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PRIMIDONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "375 MG,QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "375", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRIMIDONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PRIMIDONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "125 MG (MANE)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "125", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRIMIDONE." } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Balance disorder", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diplopia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SISODIYA S., SNADER J., PATSALOS P.. CARBAMAZEPINE TOXICITY DURING COMBINATION THERAPY WITH LEVETIRACETAM: A PHARMACODYNAMIC INTERACTION.. EPILEPSY RESEARCH.. 2002?48 (3):217?19", "literaturereference_normalized": "carbamazepine toxicity during combination therapy with levetiracetam a pharmacodynamic interaction", "qualification": "3", "reportercountry": "GB" }, "primarysourcecountry": "GB", "receiptdate": "20200812", "receivedate": "20200812", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18141327, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": 1, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" }, { "companynumb": "GB-PFIZER INC-2020276166", "fulfillexpeditecriteria": "1", "occurcountry": "GB", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "TONIC CONVULSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2000 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "TONIC CONVULSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2500 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." } ], "patientagegroup": null, "patientonsetage": "31", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diplopia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Gait disturbance", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Prescribed overdose", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SISODIYA, S.. CARBAMAZEPINE TOXICITY DURING COMBINATION THERAPY WITH LEVETIRACETAM: A PHARMACODYNAMIC INTERACTION. EPILEPSY RESEARCH. 2002?48(3):217?219", "literaturereference_normalized": "carbamazepine toxicity during combination therapy with levetiracetam a pharmacodynamic interaction", "qualification": "3", "reportercountry": "GB" }, "primarysourcecountry": "GB", "receiptdate": "20200727", "receivedate": "20200727", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18073447, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": 1, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" }, { "companynumb": "GB-MYLANLABS-2007S1013670", "fulfillexpeditecriteria": "1", "occurcountry": "GB", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "1600 MILLIGRAM, QD (800 MG, 2X/DAY (CONTROL?RELEASE))", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "076919", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG,BID (200 MG, QD)", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "076919", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG,QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "1200 MILLIGRAM, QD (600 MG, 2X/DAY)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "076919", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2000 MILLIGRAM, QD (1000 MG, 2X/DAY)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "VALPROATE SODIUM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "700 MG,BID (1400MG, QD)", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "700", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SODIUM VALPROATE" } ], "patientagegroup": null, "patientonsetage": "47", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nystagmus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Ataxia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SISODIYA S, SNADER J, PATSALOS P.. CARBAMAZEPINE TOXICITY DURING COMBINATION THERAPY WITH LEVETIRACETAM: A PHARMACODYNAMIC INTERACTION.. EPILEPSY RESEARCH. 2002?48:217?219", "literaturereference_normalized": "carbamazepine toxicity during combination therapy with levetiracetam a pharmacodynamic interaction", "qualification": "3", "reportercountry": "GB" }, "primarysourcecountry": "GB", "receiptdate": "20200812", "receivedate": "20200812", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18141318, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": 1, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" }, { "companynumb": "GB-PFIZER INC-2020276277", "fulfillexpeditecriteria": "1", "occurcountry": "GB", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "800 MG, 2X/DAY (CONTROL?RELEASE)", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "800", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "VALPROATE SODIUM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "700 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "700", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SODIUM VALPROATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." } ], "patientagegroup": null, "patientonsetage": "47", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Ataxia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Nystagmus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SISODIYA, S.. CARBAMAZEPINE TOXICITY DURING COMBINATION THERAPY WITH LEVETIRACETAM: A PHARMACODYNAMIC INTERACTION. EPILEPSY RESEARCH. 2002?48(3):217?219", "literaturereference_normalized": "carbamazepine toxicity during combination therapy with levetiracetam a pharmacodynamic interaction", "qualification": "3", "reportercountry": "GB" }, "primarysourcecountry": "GB", "receiptdate": "20200727", "receivedate": "20200727", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18073820, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": 1, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" }, { "companynumb": "GB-PFIZER INC-2020276280", "fulfillexpeditecriteria": "1", "occurcountry": "GB", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.5 MG NOCTE", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PRIMIDONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "125 MG (MANE)", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "125", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRIMIDONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MG MIDI", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, 2X/DAY (CONTROL?RELEASE)", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PRIMIDONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MG (NOCTE)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRIMIDONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.5 MG MANE", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Balance disorder", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diplopia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SISODIYA, S.. CARBAMAZEPINE TOXICITY DURING COMBINATION THERAPY WITH LEVETIRACETAM: A PHARMACODYNAMIC INTERACTION. EPILEPSY RESEARCH. 2002?48(3):217?219", "literaturereference_normalized": "carbamazepine toxicity during combination therapy with levetiracetam a pharmacodynamic interaction", "qualification": "3", "reportercountry": "GB" }, "primarysourcecountry": "GB", "receiptdate": "20200727", "receivedate": "20200727", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18073813, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": 1, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" }, { "companynumb": "GB-PFIZER INC-2020276289", "fulfillexpeditecriteria": "1", "occurcountry": "GB", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG MANE", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SEIZURE", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1500 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PHENOBARBITAL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "150 MG, 1X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "150", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PHENOBARBITONE [PHENOBARBITAL]" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "202869", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG NOCTE", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." } ], "patientagegroup": null, "patientonsetage": "57", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Ataxia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Nystagmus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SISODIYA, S.. CARBAMAZEPINE TOXICITY DURING COMBINATION THERAPY WITH LEVETIRACETAM: A PHARMACODYNAMIC INTERACTION. EPILEPSY RESEARCH. 2002?48(3):217?219", "literaturereference_normalized": "carbamazepine toxicity during combination therapy with levetiracetam a pharmacodynamic interaction", "qualification": "3", "reportercountry": "GB" }, "primarysourcecountry": "GB", "receiptdate": "20200724", "receivedate": "20200724", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18067393, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": 1, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" } ]

{ "abstract": "BACKGROUND\nMutations in QARS1, which encodes human glutaminyl-tRNA synthetase, have been associated with epilepsy, developmental regression, progressive microcephaly and cerebral atrophy. Epilepsy caused by variants in QARS1 is usually drug-resistant and intractable. Childhood onset epilepsy is also reported in various aminoacyl-tRNA synthetase disorders. We describe a case with a milder neurological phenotype than previously reported with QARS1 variants and review the seizure associations with aminoacyl-tRNA synthetase disorders.\n\n\nMETHODS\nThe patient is a 4-year-old girl presenting at 6 weeks of age with orofacial dyskinesia and hand stereotypies. She developed focal seizures at 7 months of age. Serial electroencephalograms showed shifting focality. Her seizures were controlled after introduction of carbamazepine. Progress MRI showed very mild cortical volume loss without myelination abnormalities or cerebellar atrophy. She was found to have novel compound heterozygous variants in QARS1 (NM_005051.2): c.[1132C > T];[1574G > A], p.[(Arg378Cys)];[(Arg525Gln)] originally classified as \"variants of uncertain significance\" and later upgraded to \"likely pathogenic\" based on functional testing and updated variant database review. Functional testing showed reduced solubility of the corresponding QARS1 mutants in vitro, but only mild two-fold loss in catalytic efficiency with the c.1132C > T variant and no noted change in tRNAGln aminoacylation with the c.1574G > A variant.\n\n\nCONCLUSIONS\nWe describe two QARS1 variants associated with overall conserved tRNA aminoacylation activity but characterized by significantly reduced QARS protein solubility, resulting in a milder clinical phenotype. 86% of previous patients reported with QARS1 had epilepsy and 79% were pharmaco-resistant. We also summarise literature regarding epilepsy in aminoacyl-tRNA synthetase disorders, which is also often early onset, severe and drug-refractory.", "affiliations": "Neurology Department, Sydney Children's Hospital, Sydney, Australia, School of Women's and Children's Health, UNSW Medicine, UNSW Sydney, Australia.;Université de Strasbourg, CNRS,Architecture et Réactivité de l'ARN, UPR 9002, F-67000, Strasbourg, France.;Université de Strasbourg, CNRS,Architecture et Réactivité de l'ARN, UPR 9002, F-67000, Strasbourg, France.;Rare Diseases Functional Genomics, Kids Research, Sydney Children's Hospital Network & Children's Medical Research Institute, Sydney Children's Hospital Network, Sydney, NSW 2145, Australia, Discipline of Child & Adolescent Health, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.;Sydney Genome Diagnostics, Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, Australia, Discipline of Child & Adolescent Health, Discipline of Genetic Medicine, The University of Sydney, Sydney, Australia; Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.;Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.;Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; TY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Sydney, NSW, Australia, Kids Neuroscience Centre, Kids Research, The Children's Hospital at Westmead, The University of Sydney, Sydney, NSW, Australia. Electronic address: shekeeb.mohammad@health.nsw.gov.au.", "authors": "Chan|Denise L|DL|;Rudinger-Thirion|Joëlle|J|;Frugier|Magali|M|;Riley|Lisa G|LG|;Ho|Gladys|G|;Kothur|Kavitha|K|;Mohammad|Shekeeb S|SS|", "chemical_list": null, "country": "Netherlands", "delete": false, "doi": "10.1016/j.braindev.2021.10.009", "fulltext": null, "fulltext_license": null, "issn_linking": "0387-7604", "issue": null, "journal": "Brain & development", "keywords": "ARS; Acquired microcephaly; DEE; Epilepsy; QARS; QARS1; Seizures; aminoacyl-tRNA synthetase", "medline_ta": "Brain Dev", "mesh_terms": null, "nlm_unique_id": "7909235", "other_id": null, "pages": null, "pmc": null, "pmid": "34774383", "pubdate": "2021-11-10", "publication_types": "D002363:Case Reports", "references": null, "title": "A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders.", "title_normalized": "a case of qars1 associated epileptic encephalopathy and review of epilepsy in aminoacyl trna synthetase disorders" }

[ { "companynumb": "AU-GENERIC HEALTH PTY. LTD.-2022-08833", "fulfillexpeditecriteria": "2", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "078154", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Partial seizures", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TOPIRAMATE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Partial seizures", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TOPIRAMATE" } ], "patientagegroup": "2", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Chan DL, Rudinger-Thirion J, Frugier M, Riley LG, Ho G, Kothur K et al. A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders. Brain + Development. 2022;44(2):142-147", "literaturereference_normalized": "a case of qars1 associated epileptic encephalopathy and review of epilepsy in aminoacyl trna synthetase disorders", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220622", "receivedate": "20220622", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20992267, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220721" }, { "companynumb": "AU-CIPLA LTD.-2022AU04028", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "078234", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Partial seizures", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "TOPIRAMATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Partial seizures", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TOPIRAMATE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Chan DL, Rudinger-Thirion J, Frugier M, Riley LG, Ho G, Kothur K et al. A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders. Brain-Dev. 2022;44 (2):142 to 147", "literaturereference_normalized": "a case of qars1 associated epileptic encephalopathy and review of epilepsy in aminoacyl trna synthetase disorders", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220622", "receivedate": "20220622", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20990969, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220720" }, { "companynumb": "AU-MYLANLABS-2022M1046300", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "076919", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Partial seizures", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TOPIRAMATE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "076314", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Partial seizures", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TOPIRAMATE" } ], "patientagegroup": "2", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "25.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Chan DL, Rudinger-Thirion J, Frugier M, Riley LG, Ho G, Kothur K, et al. A case of QARS1 associated epileptic encephalopathy and review of epilepsy in aminoacyl-tRNA synthetase disorders. Brain-Dev 2022;44(2):142-147.", "literaturereference_normalized": "a case of qars1 associated epileptic encephalopathy and review of epilepsy in aminoacyl trna synthetase disorders", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20220617", "receivedate": "20220617", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20975719, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220720" } ]

{ "abstract": "A 56-year-old man with a history of injection drug use and two prior episodes of native valve infective endocarditis presented with dyspnoea on exertion. Our preliminary work-up revealed bacteraemia with reported growth of 'Mycobacterium abscessus group' on multiple blood cultures. The patient was later found to have eustachian valve and prosthetic pulmonic valve endocarditis. Initially, he responded to standard antimycobacterial therapy for rapidly growing mycobacteria (RGM) with supporting laboratory susceptibilities. However, he later developed refractory disease and persistent bacteraemia in the setting of these alleged susceptible antibiotics. Further molecular testing revealed a functional and inducible erm(41) gene which confers macrolide resistance. A subspecies analysis of the M abscessus group revealed the subspecies to be abscessus We present a challenging case of M abscessus subsp. abscessus bacteraemia and prosthetic valve endocarditis with further discussion on treatment and management of this infection along with the taxonomic complexity of this ubiquitous RGM.", "affiliations": "Department of Medicine, Division of Infectious Diseases, University of Arizona College of Medicine, Tucson, Arizona, USA.;Department of Medicine, Division of Infectious Diseases, University of Arizona College of Medicine, Tucson, Arizona, USA.;Department of Medicine, Division of Infectious Diseases, University of Arizona College of Medicine, Tucson, Arizona, USA.;Department of Medicine, Baylor College of Medicine,Division of Infectious Diseases, Houston, Texas, USA.", "authors": "Beatty|Norman|N|;Brown|Craig|C|;Zangeneh|Tirdad|T|;Al Mohajer|Mayar|M|", "chemical_list": "D000900:Anti-Bacterial Agents; D008780:Methyltransferases; C035181:rRNA (adenosine-O-2'-)methyltransferase", "country": "England", "delete": false, "doi": "10.1136/bcr-2017-219618", "fulltext": null, "fulltext_license": null, "issn_linking": "1757-790X", "issue": "2017()", "journal": "BMJ case reports", "keywords": "Drugs: infectious diseases; Infections; Medical management; Valvar diseases", "medline_ta": "BMJ Case Rep", "mesh_terms": "D000900:Anti-Bacterial Agents; D003937:Diagnosis, Differential; D004417:Dyspnea; D004697:Endocarditis, Bacterial; D006350:Heart Valve Prosthesis; D006801:Humans; D008297:Male; D008780:Methyltransferases; D008875:Middle Aged; D009165:Mycobacterium Infections, Nontuberculous; D000073358:Mycobacterium abscessus; D015819:Substance Abuse, Intravenous", "nlm_unique_id": "101526291", "other_id": null, "pages": null, "pmc": null, "pmid": "28611136", "pubdate": "2017-06-13", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "12364376;13035193;19171799;21135185;23347634;25580261;25643064;26295364", "title": "A rare case of Mycobacterium abscessus subspecies abscessus prosthetic valve endocarditis and the clinical importance of inducible erm(41) gene testing.", "title_normalized": "a rare case of mycobacterium abscessus subspecies abscessus prosthetic valve endocarditis and the clinical importance of inducible erm 41 gene testing" }

[ { "companynumb": "US-APOTEX-2018AP023175", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFOXITIN SODIUM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 G, Q.6H", "drugenddate": null, "drugenddateformat": null, "drugindication": "MYCOBACTERIUM ABSCESSUS INFECTION", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "6", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "002", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFOXITIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CLARITHROMYCIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "MYCOBACTERIUM ABSCESSUS INFECTION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLARITHROMYCIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LINEZOLID" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "MYCOBACTERIUM ABSCESSUS INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LINEZOLID." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFOXITIN SODIUM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFOXITIN" } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug resistance", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "BEATTY N, BROWN C, ZANGENEH T, MOHAJER MA. A RARE CASE OF MYCOBACTERIUM ABSCESSUS SUBSPECIES ABSCESSUS PROSTHETIC VALVE ENDOCARDITIS AND THE CLINICAL IMPORTANCE OF INDUCIBLE ERM (41) GENE TESTING. DOI:10.1136/BCR-2017-219618. BMJ CASE REP. 2017?1-4", "literaturereference_normalized": "a rare case of mycobacterium abscessus subspecies abscessus prosthetic valve endocarditis and the clinical importance of inducible erm 41 gene testing", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181029", "receivedate": "20181029", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15560293, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190205" } ]

{ "abstract": "Extradural abscess has been described infrequently as a complication of extradural anaesthesia and analgesia. We describe an abscess that developed 5 days after operation in a patient who had extradural anaesthesia for Caesarean section and postoperative analgesia, and review the literature on extradural abscess complicating extradural catheterization, including a discussion on pathogenesis, clinical presentation, diagnosis and management. There have now been 16 reported cases of extradural catheter-related extradural abscess. Only one previous case has been in obstetric practice, despite the widespread use of these techniques in this specialty. A disproportionate number of cases have involved thoracic catheters. Duration of catheterization ranged from 40 h to 6 weeks, the majority of catheters being in place for 5 days or less. The time from catheter placement to development of symptoms ranged from 72 h to 5 months. The causative organism was isolated in 11 cases: Staphylococcus aureus was identified in nine (82%) and Staphylococcus epidermidis in two (18%). Outcome was reported in 15 cases, of which seven (47%) had a full or near full recovery and eight (53%) had a persistent neurological deficit. One case was managed successfully without surgery. Fifty percent of all cases have been reported in the past 5 years. With the increasing use of extradural techniques for anaesthesia and analgesia, this serious complication may be seen more frequently in the future.", "affiliations": "Department of Surgery, Wellington School of Medicine, New Zealand.", "authors": "Ngan Kee|W D|WD|;Jones|M R|MR|;Thomas|P|P|;Worth|R J|RJ|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1093/bja/69.6.647", "fulltext": null, "fulltext_license": null, "issn_linking": "0007-0912", "issue": "69(6)", "journal": "British journal of anaesthesia", "keywords": null, "medline_ta": "Br J Anaesth", "mesh_terms": "D000038:Abscess; D000328:Adult; D000767:Anesthesia, Epidural; D000773:Anesthesia, Obstetrical; D002585:Cesarean Section; D004824:Epidural Space; D005260:Female; D006801:Humans; D011183:Postoperative Complications; D011247:Pregnancy; D013203:Staphylococcal Infections", "nlm_unique_id": "0372541", "other_id": null, "pages": "647-52", "pmc": null, "pmid": "1467114", "pubdate": "1992-12", "publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review", "references": null, "title": "Extradural abscess complicating extradural anaesthesia for caesarean section.", "title_normalized": "extradural abscess complicating extradural anaesthesia for caesarean section" }

[ { "companynumb": "NZ-PFIZER INC-2020417186", "fulfillexpeditecriteria": "1", "occurcountry": "NZ", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "SODIUM BICARBONATE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "8.4% SODIUM BICARBONATE 2 ML", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SODIUM BICARBONATE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LIDOCAINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.5 % LIGNOCAINE 3 ML IN 7.5 % GLUCOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIGNOCAINE HCL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "EPINEPHRINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 UG", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ADRENALINE HCL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MEPERIDINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "008", "drugauthorizationnumb": "021171", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG, PRESERVATIVE FREE", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MEPERIDINE HCL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "EPINEPHRINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "008", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "15 UG", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "15", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ADRENALINE HCL" } ], "patientagegroup": null, "patientonsetage": "26", "patientonsetageunit": "801", "patientsex": "2", "patientweight": "80", "reaction": [ { "reactionmeddrapt": "Staphylococcal abscess", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Extradural abscess", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "NGAN KEE, W.. EXTRADURAL ABSCESS COMPLICATING EXTRADURAL ANAESTHESIA FOR CAESAREAN SECTION. BRITISH JOURNAL OF ANAESTHESIA. 1992?69 (6):647-652", "literaturereference_normalized": "extradural abscess complicating extradural anaesthesia for caesarean section", "qualification": "1", "reportercountry": "NZ" }, "primarysourcecountry": "NZ", "receiptdate": "20201106", "receivedate": "20201029", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18440489, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" } ]

{ "abstract": "OBJECTIVE\nA patient presented with convulsive seizures when sodium valproate (VPA) and tebipenem pivoxil (Orapenem) were co-administered accidentally. The seizures were suspected to be caused by a reduced concentration of VPA in the blood.\n\n\nMETHODS\nA 6-year-old boy (weight: 16 kg, at the start of treatment) began sodium valproate (valproate syrup 5%) treatment for epilepsy in February 2012. At a dose of 350 mg/day, he experienced no convulsive seizures and maintained stable symptoms for the past 9 months. In December, he was prescribed 160 mg/day tebipenem pivoxil by an otolaryngologist for inflammation of the tympanic membrane. He experienced convulsive seizures the day after beginning co-administration. The concentration of VPA in his blood at this time was 30.0 μg/mL, which was lower than the optimal blood concentration.\n\n\nCONCLUSIONS\nMarked reduction of VPA concentration in the blood due to co-administration of VPA and injectable carbapenem antibiotics has been well-documented; however, this is the first report of such an interaction with tebipenem, which is an orally-administered carbapenem antibiotic. Although the mechanism of drug interaction between VPA and carbapenem antibiotics is not fully understood, it is thought that VPA blood concentrations decrease due to production of valproic acid glucuronic acid conjugates (VPA-Gluc) being promoted directly or indirectly by carbapenem antibiotics. When we assessed the patient according to the DIPS system, we calculated a score of +4 (possibility of interaction).\n\n\nCONCLUSIONS\nThe results suggest that co-administration of oral carbapenem antibiotics and VPA should be avoided.", "affiliations": null, "authors": "Shihyakugari|Atsuko|A|;Miki|Akiko|A|;Nakamoto|Natsue|N|;Satoh|Hiroki|H|;Sawada|Yasufumi|Y|", "chemical_list": "D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D015780:Carbapenems; D014635:Valproic Acid; C500135:tebipenem", "country": "Germany", "delete": false, "doi": "10.5414/CP202188", "fulltext": null, "fulltext_license": null, "issn_linking": "0946-1965", "issue": "53(1)", "journal": "International journal of clinical pharmacology and therapeutics", "keywords": null, "medline_ta": "Int J Clin Pharmacol Ther", "mesh_terms": "D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D015780:Carbapenems; D002648:Child; D004347:Drug Interactions; D016903:Drug Monitoring; D006801:Humans; D008297:Male; D008508:Medication Errors; D019338:Polypharmacy; D012640:Seizures; D014635:Valproic Acid", "nlm_unique_id": "9423309", "other_id": null, "pages": "92-6", "pmc": null, "pmid": "25407257", "pubdate": "2015-01", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "First case report of suspected onset of convulsive seizures due to co-administration of valproic acid and tebipenem.", "title_normalized": "first case report of suspected onset of convulsive seizures due to co administration of valproic acid and tebipenem" }

[ { "companynumb": "JP-MYLANLABS-2015M1006243", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LACTOBACILLUS ACIDOPHILUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2G/DAY; TWICE DAILY, EVERY 12 HOURS EXTENDED FOR 7 DAYS.", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20121226", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LACTOBACILLUS" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BECLOMETHASONE DIPROPIONATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 DAILY SPRAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20121218", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BECLOMETASONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MONTELUKAST SODIUM" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20121213", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MONTELUKAST" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFDITOREN PIVOXIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20121213", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFDITOREN PIVOXIL." }, { "actiondrug": "3", "activesubstance": { "activesubstancename": "VALPROATE SODIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "077567", "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20120201", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VALPROATE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "TEBIPENEM PIVOXIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "160 MG/DAY (TWICE DAILY, EVERY 12 HOURS)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20121226", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ORAPENEM" }, { "actiondrug": "3", "activesubstance": { "activesubstancename": "VALPROATE SODIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "077567", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "350 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20120314", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VALPROATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBOCYSTEINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20121213", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOCISTEINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LACTOBACILLUS ACIDOPHILUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2G/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20121213", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LACTOBACILLUS" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MEQUITAZINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1.8 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20121213", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MEQUITAZINE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug administration error", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Epilepsy", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20121227" } }, "primarysource": { "literaturereference": "SHIHYAKUGARI A, MIKI A, NAKAMOTO N, SATOH H, SAWADA Y. FIRST CASE REPORT OF SUSPECTED ONSET OF CONVULSIVE SEIZURES DUE TO CO-ADMINISTRATION OF VALPROIC ACID AND TEBIPENEM. INT-J-CLIN-PHARMACOL-THER 2015; 53(1):92-96.", "literaturereference_normalized": "first case report of suspected onset of convulsive seizures due to co administration of valproic acid and tebipenem", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20150227", "receivedate": "20150227", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10874612, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" } ]

{ "abstract": "Multiple myeloma (MM) typically presents with hypercalcemia, renal insufficiency, anemia, and bone lesions. Elevated ammonia level manifesting as altered mental status is a rare complication in MM. We report an interesting case of hyperammonemic encephalopathy in a 73-year-old male with advanced relapsing kappa-light chain MM.", "affiliations": "Department of Internal Medicine, Advocate Christ Medical Center, Oak Lawn, IL, USA.;Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.;Department of Internal Medicine, Advocate Christ Medical Center, Oak Lawn, IL, USA.;Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.;Department of Internal Medicine, Advocate Christ Medical Center, Oak Lawn, IL, USA.;Department of Internal Medicine, Advocate Christ Medical Center, Oak Lawn, IL, USA.", "authors": "Murtaza|Ghulam|G|;Lu|Hannah|H|;Faqah|Anadil|A|;Konowitz|Nicholas|N|;Kuruvilla|Aneesh|A|;Adhikari|Sujeen|S|", "chemical_list": null, "country": "Canada", "delete": false, "doi": "10.14740/jh322e", "fulltext": "\n==== Front\nJ Hematol\nJ Hematol\nElmer Press\nJournal of Hematology\n1927-1212 1927-1220 Elmer Press \n\n32300389\n10.14740/jh322e\nCase Report\nMultiple Myeloma-Induced Hyperammonemic Encephalopathy\nMM-Induced Hyperammonemic EncephalopathyMurtaza Ghulam ac Lu Hannah b Faqah Anadil a Konowitz Nicholas b Kuruvilla Aneesh a Adhikari Sujeen a a Department of Internal Medicine, Advocate Christ Medical Center, Oak Lawn, IL, USA\nb Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA\nc Corresponding Author: Ghulam Murtaza, Department of Internal Medicine, Advocate Christ Medical Center, 4440 W 95th St., Oak Lawn, IL 60453, USA. Email: ghlmurtaza@gmail.com\n3 2017 \n21 3 2017 \n6 1 29 31\n06 3 2017 Copyright 2017, Murtaza et al.2017This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Multiple myeloma (MM) typically presents with hypercalcemia, renal insufficiency, anemia, and bone lesions. Elevated ammonia level manifesting as altered mental status is a rare complication in MM. We report an interesting case of hyperammonemic encephalopathy in a 73-year-old male with advanced relapsing kappa-light chain MM.\n\nAbdominal painPancreatitisRenal cell carcinomaPazopanib\n==== Body\nIntroduction\nMultiple myeloma (MM) is a neoplastic, monoclonal proliferation of terminally differentiated plasma cells. It is characterized by plasma cell bone marrow infiltration and accumulation of monoclonal protein in the serum and urine [1]. MM is the second most common hematologic neoplasm, with a 1 in 143 lifetime risk and 5-year survival rate of 47%. In 2015, an estimated 30,300 people were diagnosed with the disease and an estimated 12,650 deaths resulted directly from MM and its complications [2]. Treatment for MM in the past decade has improved dramatically with the advent of three novel targeted agents: proteasome inhibitor bortezomib, immunomodulatory agent, thalidomide, and its analog lenalidomide. With these novel agents, the total healthcare cost of MM amounts to a mean estimate of $118,353 per treatment episode [3]. While MM presents with a variety of disease-related complications, the most common complications include the following: hypercalcemia, renal insufficiency, anemia, and bone lesions [2, 3]. The complication of altered mental status in MM is usually secondary to hypercalcemia, hyperviscosity, or uremia; hyperammonemia is a rare reported cause of altered mental status in an MM patient.\n\nHyperammonemia is typically found in chronic liver diseases with portal-systemic shunts and acute fulminant hepatic failure [4]. It has also been described in hematologic malignancies such as acute leukemia and following bone marrow transplantation [5, 6]. We report a rare case of hyperammonemic encephalopathy in a 73-year-old African American male with advanced relapsing kappa-light chain MM.\n\nCase Report\nThree years ago in June 2013, our patient with no relevant medical history presented with worsening fatigue, and was diagnosed with kappa-light chain MM. At the time of diagnosis, he was anemic (8.4 g/dL), hypercalcemic (14.4 mg/dL), thrombocytopenic (88,000/μL), and had acute kidney injury (BUN 52 mg/dL and creatinine 5.7 mg/dL). He had low serum immunoglobulins (IgA 27 mg/dL, IgG 376 mg/dL, and IgM 9 mg/dL), high serum kappa free light chain (1,082.50 mg/dL), normal serum lambda free light chain (0.98 mg/dL), low protein electrophoresis (5.3 g/dL), high M protein (0.1 g/dL), low C3 (85 mg/dL), normal C4 (19.6 mg/dL), and high kappa/lambda ratio (1,104.59). He was placed on hemodialysis to manage his renal failure and treated with proteasome inhibitor bortezomib and dexamethasone. He responded well to the therapy, with a reduction of kappa-light chain from 1,082.50 to 505 mg/dL. In February 2014, his MM relapsed, and he began second-line chemotherapy with immunomodulatory agent thalidomide and dexamethasone. His MM continued to progress, and after achieving an inadequate response, he was started on third-line therapy with immunomodulatory agent lenalidomide and dexamethasone. By April 2016, his MM continued to worsen and he was requiring frequent transfusions. Lenalidomide had been on hold for several months due to his severe cytopenia. After restarting lenalidomide, his platelet counts improved, but his disease progressed and now showed plasma cell leukemia. Having already failed three other drug treatments, the patient was started on a fourth chemotherapy treatment, monoclonal antibody daratumumab, with dexamethasone, tylenol, and benadryl. His end-stage renal failure and cytopenia excluded the option of other chemotherapy treatments.\n\nAfter his first dose treatment of daratumumab, the patient became progressively lethargic. Prior to treatment, he was oriented to self and place, and ambulated to the hospital.\n\nVitals showed that the patient was afebrile 36.9 °C, normotensive BP 101/55, pulse 92, and saturating 90% on room air. Laboratory findings revealed leukocytosis (white blood cell count 25,700/μL, with a differential of 35% plasma cells), anemia (8 g/dL), thrombocytopenia (49,000/μL), and hypercalcemia (10.6 mg/dL). Blood sodium and glucose levels were normal, as were liver function tests (bilirubin 0.7 mg/dL, ALT 53 units/L, AST 56 units/L, and alkaline phosphatase 80 units/L) and prothrombin time. Consistent with the patient’s end-stage renal disease, BUN (31 mg/dL) and creatinine (7.62 mg/dL) were elevated. Rapid neurologic deterioration ensued and the patient became confused and unresponsive to verbal stimuli. He did not have neck stiffness or signs of meningismus. In evaluation of the patient’s altered mental status, a CT scan of the head and MRI of the brain were performed and were negative for acute infarct, hemorrhage, mass, or midline shift. Liver function tests and abdominal CT scan showed no evidence of hepatic dysfunction. The patient had not received salicylates and blood and urine cultures were found to be negative. Ammonia levels were sent and he was confirmed to have an encephalopathic picture with elevated ammonia of 120 mg/dL (normal value < 47 mg/dL). The patient was promptly started on lactulose, rifaximin, empiric antibiotics vancomycin and cefepime and antiviral treatment acyclovir. Through the next 4 days, his elevated ammonia levels did not resolve: 120 mg/dL → 95 mg/dL → 120 mg/dL → 127 mg/dL. With findings suggestive of MM-induced hyperammonemic encephalopathy, our next step in treatment would have been aggressive chemotherapy with high dose cyclophosphamide. But, considering his severe cytopenia and failure to respond to prior chemotherapy, the patient was deemed a poor candidate for further aggressive treatment. After discussion with the family, the decision was made to withdraw active treatment and our patient died within 5 days from disease progression.\n\nDiscussion\nHyperammonemic encephalopathy in the absence of liver disease is a rare complication of advanced MM that has a high mortality. It is usually characterized by lethargy, confusion, and asterixis, with rapid progression to coma and death. Literature review suggests that most cases of hyperammonemic encephalopathy are MM IgA subtype and chemotherapy-resistant. The etiology of this disease has yet to be determined. Currently, there is no consensus on management (Table 1) [7-9].\n\nTable 1 Published Treatment Regimens and Outcomes for MM-Induced Hyperammonemic Encephalopathy\nTreatment\tOutcome\t\nBortezomib + cyclophosphamide + dexamethasone [11]\tPatient released home after 11 days.\t\nBortezomib + high dose dexamethasone + bendamustine [6]\tPatient died 2 weeks after treatment due to aspiration pneumonia.\t\nSimultaneous continuous venovenous hemodialysis and extended daily hemodialysis\nVincristine + high dose dexamethasone [12]\tPatient with medically refractory hyperammonemia survived and was discharged home.\t\nSome studies report beneficial effects in using hemodialysis to remove excess ammonia [9, 10]. Several others suggest that the initiation of aggressive chemotherapy is the most effective measure to achieve normal ammonia levels and clinical improvement [7]. Unfortunately, our patient was severely cytopenic and a poor candidate for chemotherapy treatment when he presented with hyperammonemic encephalopathy.\n\nLittle is known about the underlying pathophysiology of hyperammonemic encephalopathy as a complication of MM. One study demonstrated excess production of ammonia in vitro by human myeloma cell lines, although the mechanism is unclear. Whether this overproduction is due to mutations in the enzymes involved in ammonia synthesis or due to excess protein synthesis remains unknown [11]. Hyperammonemic encephalopathy has also been infrequently reported to occur after high dose chemotherapy for treatment of hematologic malignancies [6]. No cases have been reported to specifically describe daratumumab-induced hyperammonemia, but considering our patient’s acute change in mental status following chemotherapy treatment, its contributions to the clinical presentation cannot be ignored.\n\nThe characteristics of hyperammonemic encephalopathy secondary to MM have also not been well studied. One review reports three cases that show an association of the appearance of peripheral blood myeloma cells to the development of hyperammonemic encephalopathy [12]. Our case supports this rare association, with our patient’s altered mental status developing shortly following his progression to plasma cell leukemia (plasma cells comprising 35% of the white blood count).\n\nConclusion\nWe emphasize the need for a better understanding of the etiology of the hyperammonemic encephalopathy, its prognostic factors, and alternate treatment modalities for MM patients unable to undergo chemotherapy. Most importantly, patients with relapsing MM who present with altered mental status without a clear cause should be promptly evaluated for primary hyperammonemic encephalopathy as a potential cause.\n\nFinancial Disclosures\nWe do not have any financial disclosures nor have we received any funding.\n\nConflicts of Interest\nThere are no conflicts of interest.\n\nConsent\nConsent was obtained.\n==== Refs\nReferences\n1 Jones FM Bokhari SW Hyperammonemic encephalopathy in multiple myeloma Ann Hematol 2014 93 8 1431 1432 10.1007/s00277-013-1973-0 24292538 \n2 Multiple Myeloma: Statistics. Cancer Net American Society of Clinical Oncology 2016 \n3 Teitelbaum A Ba-Mancini A Huang H Henk HJ Health care costs and resource utilization, including patient burden, associated with novel-agent-based treatment versus other therapies for multiple myeloma: findings using real-world claims data Oncologist 2013 18 1 37 45 10.1634/theoncologist.2012-0113 23299776 \n4 Fraser CL Arieff AI Hepatic encephalopathy N Engl J Med 1985 313 14 865 873 10.1056/NEJM198510033131406 2993889 \n5 Watson AJ Chambers T Karp JE Risch VR Walker WG Brusilow SW Transient idiopathic hyperammonaemia in adults Lancet 1985 2 8467 1271 1274 10.1016/S0140-6736(85)91554-5 2866337 \n6 Mitchell RB Wagner JE Karp JE Watson AJ Brusilow SW Przepiorka D Storb R et al Syndrome of idiopathic hyperammonemia after high-dose chemotherapy: review of nine cases Am J Med 1988 85 5 662 667 10.1016/S0002-9343(88)80239-0 3189370 \n7 Howman R Thakerer A Pitman M Ding N Thompson PA Khot A Harrison SJ Bortezomib, cyclophosphamide, and dexamethasone: highly effective for rapid reversal of myeloma-associated hyperammonemic encephalopathy Leuk Lymphoma 2010 51 12 2299 2302 10.3109/10428194.2010.518654 20929329 \n8 Oestmann A Aujesky D [Hyperammonemic encephalopathy in multiple myeloma] Dtsch Med Wochenschr 2014 139 30 1518 1520 10.1055/s-0034-1370132 25072861 \n9 Brucculeri M Gabbard W Masson J Jooma N Simultaneous double hemodialysis for the control of refractory hyperammonemia Int J Artif Organs 2013 36 2 135 138 10.5301/ijao.5000177 23404638 \n10 Lora-Tamayo J Palom X Sarra J Gasch O Isern V Fernandez de Sevilla A Pujol R Multiple myeloma and hyperammonemic encephalopathy: review of 27 cases Clin Lymphoma Myeloma 2008 8 6 363 369 10.3816/CLM.2008.n.054 19064403 \n11 Kwan L Wang C Levitt L Hyperammonemic encephalopathy in multiple myeloma N Engl J Med 2002 346 21 1674 1675 10.1056/NEJM200205233462119 12024007 \n12 Ikewaki J Ogata M Imamura T Kohno K Nakayama T Kadota J Development of hyperammonemic encephalopathy in patients with multiple myeloma may be associated with the appearance of peripheral blood myeloma cells Leuk Lymphoma 2009 50 4 667 669 10.1080/10428190902741489 19373670\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "1927-1212", "issue": "6(1)", "journal": "Journal of hematology", "keywords": "Abdominal pain; Pancreatitis; Pazopanib; Renal cell carcinoma", "medline_ta": "J Hematol", "mesh_terms": null, "nlm_unique_id": "101635099", "other_id": null, "pages": "29-31", "pmc": null, "pmid": "32300389", "pubdate": "2017-03", "publication_types": "D002363:Case Reports", "references": "3189370;20929329;25072861;24292538;19064403;2993889;2866337;23404638;23299776;19373670;12024007", "title": "Multiple Myeloma-Induced Hyperammonemic Encephalopathy.", "title_normalized": "multiple myeloma induced hyperammonemic encephalopathy" }

[ { "companynumb": "US-JNJFOC-20170627780", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "DARATUMUMAB" }, "drugadditional": "2", "drugadministrationroute": "042", "drugauthorizationnumb": "761036", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CONCENTRATE FOR SOLUTION FOR INFUSION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DARATUMUMAB" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "2", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DIPHENHYDRAMINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNSPECIFIED", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BENADRYL" } ], "patientagegroup": "6", "patientonsetage": "73", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Disease progression", "reactionmeddraversionpt": "21.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Hyperammonaemic encephalopathy", "reactionmeddraversionpt": "21.0", "reactionoutcome": "3" } ], "summary": null }, "primarysource": { "literaturereference": "MURTAZA G, FAQAH A, LU H, KONOWITZ N. MULTIPLE MYELOMA INDUCED HYPERAMMONEMIC ENCEPHALOPATHY. INVESTIGATIVE MEDICINE AMERICAN FEDERATION FOR MEDICAL RESEARCH MIDWESTERN REGIONALMEETING 01?APR?2017?65 (4):845.", "literaturereference_normalized": "multiple myeloma induced hyperammonemic encephalopathy", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20180711", "receivedate": "20170705", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13717144, "safetyreportversion": 4, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20181010" } ]

{ "abstract": "Leptomeningeal disease is a rare complication of chronic lymphocytic leukemia (CLL). We report a case of leptomeningeal disease in CLL with a complete clinical response and clearance of cerebral spinal fluid (CSF) after treatment with ibrutinib and intrathecal rituximab. In a comprehensive review of the published literature since 1976, we found 136 cases of CLL with leptomeningeal spread. We found that leptomeningeal disease in patients with CLL responds favorably to treatment in most cases and is associated with longer overall survival than is expected for other cancers. Clearance of CSF is associated with improved survival. Treatment with rituximab and ibrutinib is more frequently associated with complete response compared with older agents. IMPLICATIONS FOR PRACTICE: The incidence of leptomeningeal CLL is more common than previously described and can be recognized by attention to certain symptoms and signs. This case presentation and literature review reveals that, in many cases, leptomeningeal lymphomatosis is reversible with the use of rituximab and ibrutinib. The authors show a survival benefit associated with treating to cerebral spinal fluid (CSF) clearance by cytology and compare outcomes with various treatment strategies, focusing on novel agents. Now that there is effective therapy for leptomeningeal lymphoma in CLL, the importance for oncologists to recognize this neurologic complication has become clear.", "affiliations": "Department of Neurology, University of Washington, Seattle, Washington, USA alipi@uw.edu.;Department of Neurology, University of Washington, Seattle, Washington, USA.", "authors": "Naydenov|Alipi V|AV|0000-0003-0340-2008;Taylor|Lynne P|LP|", "chemical_list": "D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D000069283:Rituximab; D000225:Adenine", "country": "United States", "delete": false, "doi": "10.1634/theoncologist.2018-0619", "fulltext": null, "fulltext_license": null, "issn_linking": "1083-7159", "issue": "24(9)", "journal": "The oncologist", "keywords": "CLL; chronic lymphocytic leukemia; leptomeningeal carcinomatosis", "medline_ta": "Oncologist", "mesh_terms": "D000225:Adenine; D000971:Antineoplastic Combined Chemotherapy Protocols; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D008297:Male; D055756:Meningeal Carcinomatosis; D008875:Middle Aged; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; D012074:Remission Induction; D000069283:Rituximab", "nlm_unique_id": "9607837", "other_id": null, "pages": "1237-1245", "pmc": null, "pmid": "30842245", "pubdate": "2019-09", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "10192427;10382945;10950515;11061073;11074639;11302253;11843801;11908730;12185514;12411991;12446533;12554011;1264648;12853692;12916878;1371713;1414160;15159510;15337619;15360010;15937434;16019494;1623453;16236614;16247665;1642098;17483076;17570037;17850954;18216293;18446313;19100998;19224854;19664708;20487439;20598636;21212432;21769650;2272142;2294692;23332395;23650405;24237449;24450857;2496549;25218117;25700432;26275952;26436987;26819053;26915463;27458945;2766225;27858991;2790684;29707738;3090818;310337;3341285;3358732;3474054;3491759;3594356;3802037;3872161;3874689;445372;6575578;6603668;6884398;6895047;7119204;7178833;7850707;7892133;8410140;8418408;8559372;9150717;9167611;9613992;9692402;9728609;9767335;9929115", "title": "Leptomeningeal Carcinomatosis in Chronic Lymphocytic Leukemia: A Case Report and Review of the Literature.", "title_normalized": "leptomeningeal carcinomatosis in chronic lymphocytic leukemia a case report and review of the literature" }

[ { "companynumb": "US-TEVA-2019-US-1142696", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "VENETOCLAX" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": "201511", "drugenddateformat": "610", "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VENETOCLAX." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": "201511", "drugenddateformat": "610", "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "BENDAMUSTINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "022249", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": "201511", "drugenddateformat": "610", "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BENDAMUSTINE" } ], "patientagegroup": null, "patientonsetage": "7", "patientonsetageunit": "800", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Stomatitis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAYDENOV AV, TAYLOR LP. LEPTOMENINGEAL CARCINOMATOSIS IN CHRONIC LYMPHOCYTIC LEUKEMIA: A CASE REPORT AND REVIEW OF THE LITERATURE. ONCOLOGIST 2019?24(9):1237-1245.", "literaturereference_normalized": "leptomeningeal carcinomatosis in chronic lymphocytic leukemia a case report and review of the literature", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20191127", "receivedate": "20191127", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17083006, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200122" }, { "companynumb": "US-ABBVIE-19K-163-2991590-00", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "VENETOCLAX" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "208573", "drugbatchnumb": "NOT AVAILABLE", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LEUKOCYTOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VENETOCLAX." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "NOT AVAILABLE", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LEUKOCYTOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "BENDAMUSTINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "NOT AVAILABLE", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LEUKOCYTOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BENDAMUSTINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "FOR FOUR DOSES", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "2", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IBRUTINIB" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBRUTINIB" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GABAPENTIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GABAPENTIN." } ], "patientagegroup": null, "patientonsetage": "58", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Metastases to meninges", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAYDENOV A, TAYLOR L. LEPTOMENINGEAL CARCINOMATOSIS IN CHRONIC LYMPHOCYTIC LEUKEMIA: A CASE REPORT AND REVIEW OF THE LITERATURE. THE ONCOLOGIST. 2019?24 (9):1237-1245.", "literaturereference_normalized": "leptomeningeal carcinomatosis in chronic lymphocytic leukemia a case report and review of the literature", "qualification": "1", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20191105", "receivedate": "20191105", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16996012, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200122" } ]

{ "abstract": "Here, we report the case of a patient with small-cell lung carcinoma (SCLC) who developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This syndrome may be associated with chemotherapy-induced tumour lysis. Our patient was successfully treated with tolvaptan. A 70-year-old man was diagnosed with SCLC and was treated with carboplatin and etoposide. Episodes of hyponatremia occurred after every four cycles of chemotherapy that achieved tumour reduction; however, the hyponatremia was improved by temporary administration of tolvaptan. In SIADH associated with chemotherapy-induced tumour lysis, tolvaptan may improve hyponatremia and enable the continued administration of effective chemotherapy.", "affiliations": "Department of Respiratory Medicine Fujieda Municipal General Hospital Fujieda Japan.;Department of Respiratory Medicine Fujieda Municipal General Hospital Fujieda Japan.;Department of Respiratory Medicine Fujieda Municipal General Hospital Fujieda Japan.;Department of Respiratory Medicine Fujieda Municipal General Hospital Fujieda Japan.;Department of Respiratory Medicine Fujieda Municipal General Hospital Fujieda Japan.;Second Division, Department of Internal Medicine Hamamatsu University School of Medicine Hamamatsu Japan.", "authors": "Miyashita|Koichi|K|0000-0003-3550-1182;Matsuura|Shun|S|;Naoi|Hyogo|H|;Tsukui|Masaru|M|;Koshimizu|Naoki|N|;Suda|Takafumi|T|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1002/rcr2.296", "fulltext": "\n==== Front\nRespirol Case RepRespirol Case Rep10.1002/(ISSN)2051-3380RCR2Respirology Case Reports2051-3380John Wiley & Sons, Ltd Chichester, UK 10.1002/rcr2.296RCR2296Case ReportCase ReportsSuccessful treatment by tolvaptan of the syndrome of inappropriate antidiuretic hormone secretion that may be associated with chemotherapy‐induced tumour lysis in a patient with small‐cell lung carcinoma SIADH associated with tumour lysisK. Miyashita et al.Miyashita Koichi http://orcid.org/0000-0003-3550-1182koichim501@yahoo.co.jp \n1\nMatsuura Shun \n1\nNaoi Hyogo \n1\nTsukui Masaru \n1\nKoshimizu Naoki \n1\nSuda Takafumi \n2\n\n1 \nDepartment of Respiratory Medicine\nFujieda Municipal General Hospital\nFujieda\nJapan\n\n2 \nSecond Division, Department of Internal Medicine\nHamamatsu University School of Medicine\nHamamatsu\nJapan\n* Correspondence\n\nKoichi Miyashita, Department of Respiratory Medicine, Fujieda Municipal General Hospital, 4‐1‐11 Surugadai, Fujieda, Shizuoka 426‐8677, Japan. E‐mail: koichim501@yahoo.co.jp\n26 1 2018 4 2018 6 3 10.1002/rcr2.v6.3e0029620 10 2017 05 12 2017 14 12 2017 © 2018 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of RespirologyThis is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Here, we report the case of a patient with small‐cell lung carcinoma (SCLC) who developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This syndrome may be associated with chemotherapy‐induced tumour lysis. Our patient was successfully treated with tolvaptan. A 70‐year‐old man was diagnosed with SCLC and was treated with carboplatin and etoposide. Episodes of hyponatremia occurred after every four cycles of chemotherapy that achieved tumour reduction; however, the hyponatremia was improved by temporary administration of tolvaptan. In SIADH associated with chemotherapy‐induced tumour lysis, tolvaptan may improve hyponatremia and enable the continued administration of effective chemotherapy.\n\nsmall‐cell lung carcinomasyndrome of inappropriate antidiuretic hormone secretiontolvaptantumour lysis source-schema-version-number2.0component-idrcr2296cover-dateApril 2018details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.8.2 mode:remove_FC converted:21.05.2018\n\n\nMiyashita , K. \n, \nMatsuura , S. \n, \nNaoi , H. \n, \nTsukui , M. \n, \nKoshimizu , N. \n and \nSuda , T. \n (2018 ) Successful treatment by tolvaptan of the syndrome of inappropriate antidiuretic hormone secretion that may be associated with chemotherapy‐induced tumour lysis in a patient with small‐cell lung carcinoma . Respirology Case Reports , 6 (3 ), e00296. doi: 10.1002/rcr2.296.\n\n\nAssociate Editor: Wai‐Cho Yu\n==== Body\nIntroduction\nThe syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an important complication in a patient with small‐cell lung carcinoma (SCLC) and is usually diagnosed before treatment. Both antitumor agents and tumour lysis can cause SIADH after chemotherapy. Treatment of hyponatremia with SIADH is crucial to continue chemotherapy. Hypertonic saline and fluid restriction can be used to improve hyponatremia, and recently, tolvaptan (a vasopressin‐2‐receptor antagonist) has been reported to improve SIADH in SCLC patients 1. However, there have been no reports of SIADH associated with chemotherapy‐induced tumour lysis treated with tolvaptan. We describe a case of an SCLC patient with decreases in sodium levels that developed after four cycles of chemotherapy each and that was improved by tolvaptan.\n\nCase Report\nA 70‐year‐old man who had been treated with amlodipine for hypertension was referred to our hospital because of coughing for 2 months. A chest X‐ray showed upper lung field infiltration and an abnormally high position of the diaphragm (Fig. 1). Chest computed tomography (CT) revealed a mass lesion in the right upper lobe and pleural fluid. Haematological examination showed normal sodium levels of 142 mEq/L. Serum levels of pro‐gastrin‐releasing peptide (ProGRP) and neuron‐specific enolase (NSE) were 36,700 pg/mL and 306 ng/mL, respectively. Cytopathological examination of the pleural fluid indicated small‐cell carcinoma. Staging revealed hepatic metastasis, but magnetic resonance imaging (MRI) of the head showed no metastasis.\n\nFigure 1 Chest X‐ray showed upper lung field infiltration at diagnosis (A). After one cycle of carboplatin and etoposide (B). After four cycles of carboplatin and etoposide (C).\n\nChemotherapy with carboplatin (AUC = 5) and etoposide (100 mg/m2) was initiated. The patient’s serum sodium levels decreased, and 11 days after initiation of chemotherapy, he developed asymptomatic hyponatremia (114 mEq/L), with a decreased serum osmolarity of 239 mOsm/L (Fig. 2). His thyroid, renal, and adrenal functions were normal. His urine osmolarity was 538 mOsm/L, and his urine sodium was 112 mEq/L. His plasma antidiuretic hormone secretion (ADH) was 6.1 pg/mL, which is unusual for hyponatremia. A diagnosis of SIADH was made based on the accepted diagnostic criteria 2.\n\nFigure 2 Clinical course of the patient. In the upper part of the diagram, each drug used for the treatment of SIADH and small‐cell lung carcinoma is shown. In the lower part, transitional serum levels of sodium and pro‐gastrin‐releasing peptide (ProGRP) are demonstrated.\n\nHypertonic saline infusion and fluid restriction did not result in a sufficient improvement of his serum sodium level. Subsequently, those treatments for hyponatremia were discontinued, and the administration of low doses of tolvaptan (7.5 mg/day) was started. His serum sodium level was improved after initiation without an excessive increase (> 12 mEq/L over 24 h).\n\nAfter 5 days, the tolvaptan was stopped, and his serum sodium level normalized 10 days later. A chest X‐ray showed a reduction in tumour size, and the serum level of ProGRP was 6650 pg/mL, indicating that the chemotherapy was effective. We decided to continue carboplatin and etoposide. His second to fourth cycles of chemotherapy induced hyponatremia repetitively, and short‐term tolvaptan improved his hyponatremia. He received a total of four cycles of carboplatin and etoposide, and then, tolvaptan was stopped. After a month, CT showed that the hepatic metastasis had increased in size, and the hyponatremia had recurred, suggesting the tumour had the ability to produce ADH. Hypertonic saline infusion and fluid restriction were not sufficient to improve his serum sodium level, but administration of tolvaptan improved his hyponatremia. He was administered amrubicin (35 mg/m2) as second‐line chemotherapy, and hyponatremia did not occur during the continuation of tolvaptan treatment.\n\nDiscussion\nWe have described a case of SIADH that was treated by tolvaptan following effective chemotherapy, which may be associated with chemotherapy‐induced tumour lysis. In such cases, tolvaptan may alleviate hyponatremia and enable the continuation of effective chemotherapy.\n\nSIADH has been reported in approximately 10% of patients with SCLC 3. Hyponatremia is usually detected on presentation as paraneoplastic SIADH, caused by the release of ADH/ADH‐like substances from the tumour. Hyponatremia can improve with tumour regression by effective chemotherapy. Even though SIADH resolves with chemotherapy, hyponatremia often recurs at the time of tumour relapse [4]. In this case, SIADH occurred after effective chemotherapy, although hyponatremia did not occur before the first course of chemotherapy. It is rare for hyponatremia to occur after chemotherapy compared to before chemotherapy. We presumed that the cause of SIADH was an administered drug (carboplatin or etoposide) or chemotherapy‐induced tumour lysis. However, it is difficult to differentiate the cause because both are expected to occur after effective chemotherapy, and both improve after the treatment course. One month after the fourth cycle of chemotherapy, SIADH recurred with tumour progression, suggesting that the growing tumour, which had been reduced by chemotherapy, could produce ADH. Subsequent recurrence and concurrent SIADH without chemotherapy indicated that an anticancer drug was not implicated at the time of tumour relapse. The clinical course lent support to the hypothesis that the previous episode of SIADH was not due to an anticancer drug. Therefore, we diagnosed the patient with SIADH that was induced by tumour lysis.\n\nTolvaptan is sufficient to stabilize sodium levels in SIADH associated with chemotherapy‐induced tumour lysis. Retrospective data showed that hyponatremia and the lack of correction of sodium can lead to a poor outcome in SCLC patients 5. Correction and stabilization of the sodium levels are required before continuing chemotherapy treatment 1. In general terms, hypertonic saline and fluid restriction are first administered to correct hyponatremia in SIADH. Pharmacology therapy such as tolvaptan has been effective in SIADH when those therapies are insufficient. In SCLC patients with SIADH, tolvaptan has been reported to achieve correction of the sodium level and commencement of chemotherapy 1.\n\nIn the present case, hypertonic saline and fluid restriction did not correct the sodium level sufficiently, whereas tolvaptan did. It has been reported that fluid restriction 6 and fludrocortisone 7 are effective to treat SIADH associated with chemotherapy‐induced tumour lysis. However, to the best of our knowledge, there have been no previous reports of cases with SIADH associated with chemotherapy‐induced tumour lysis treated with tolvaptan. In the present case, despite severe hyponatremia for which control by hypertonic saline and fluid restriction was inadequate, we decided to continue chemotherapy and completed four cycles with tolvaptan treatment.\n\nIn SIADH associated with chemotherapy‐induced tumour lysis, tolvaptan may increase the possibility of continuing effective chemotherapy.\n\nDisclosure Statement\nAppropriate written informed consent was obtained for the publication of this case report and accompanying images.\n==== Refs\nReferences\n1 \n\nPetereit \nC \n, \nZaba \nO \n, \nTeber \nI \n, et al. 2013 \nA rapid and efficient way to manage hyponatremia in patients with SIADH and small cell lung cancer: treatment with tolvaptan . BMC Pulm. Med. \n13 :55 .23987478 \n2 \n\nBartter \nFC \n, and \nSchwartz \nWB \n. 1967 \nThe syndrome of inappropriate secretion of antidiuretic hormone . Am. J. Med. \n42 :790 –780 .5337379 \n3 \n\nVanhees \nSL \n, \nParidaens \nR \n, and \nVansteenkiste \nJF \n. 2000 \nSyndrome of inappropriate antidiuretic hormone associated with chemotherapy‐induced tumour lysis in small‐cell lung cancer: case report and literature review . Ann. Oncol. \n11 :1061 –1065 .11038047 \n4 \n\nList \nAF \n, \nHainsworth \nJD \n, \nDavis \nBW \n, et al. 1986 \nThe syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in small‐cell lung cancer . J. Clin. Oncol. \n4 :1191 –1198 .3016206 \n5 \n\nHansen \nO \n, \nSørensen \nP \n, and \nHansen \nKH \n. 2010 \nThe occurrence of hyponatremia in SCLC and the influence on prognosis: a retrospective study of 453 patients treated in a single institution in a 10‐year period . Lung Cancer \n68 :111 –114 .19535164 \n6 \n\nSaintigny \nP \n, \nChouahnia \nK \n, \nCohen \nR \n, et al. 2007 \nTumor lysis associated with sudden onset of syndrome of inappropriate antidiuretic hormone secretion . Clin. Lung Cancer . 8 :282–284.\n7 \n\nJaal \nJ \n, \nJõgi \nT \n, and \nAltraja \nA \n. 2015 \nSmall cell lung cancer patient with profound hyponatremia and acute neurological symptoms: an effective treatment with fludrocortisone . Case Rep. Oncol. Med. \n2015 :286029 .26240768\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "2051-3380", "issue": "6(3)", "journal": "Respirology case reports", "keywords": "small‐cell lung carcinoma; syndrome of inappropriate antidiuretic hormone secretion; tolvaptan; tumour lysis", "medline_ta": "Respirol Case Rep", "mesh_terms": null, "nlm_unique_id": "101631052", "other_id": null, "pages": "e00296", "pmc": null, "pmid": "29796276", "pubdate": "2018-04", "publication_types": "D002363:Case Reports", "references": "11038047;17311695;26240768;23987478;5337379;19535164;3016206", "title": "Successful treatment by tolvaptan of the syndrome of inappropriate antidiuretic hormone secretion that may be associated with chemotherapy-induced tumour lysis in a patient with small-cell lung carcinoma.", "title_normalized": "successful treatment by tolvaptan of the syndrome of inappropriate antidiuretic hormone secretion that may be associated with chemotherapy induced tumour lysis in a patient with small cell lung carcinoma" }

[ { "companynumb": "JP-TEVA-2018-JP-868857", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMLODIPINE BESYLATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPERTENSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMLODIPINE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "74284", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL LUNG CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Tumour lysis syndrome" }, { "drugrecuraction": "Inappropriate antidiuretic hormone secretion" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "77269", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "AUC=5", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL LUNG CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "1", "drugrecurrence": [ { "drugrecuraction": "Tumour lysis syndrome" }, { "drugrecuraction": "Inappropriate antidiuretic hormone secretion" } ], "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tumour lysis syndrome", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "MIYASHITA K, MATSUURA S, NAOI H, TSUKUI M, KOSHIMIZU N, SUDA T. SUCCESSFUL TREATMENT BY TOLVAPTAN OF THE SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION THAT MAY BE ASSOCIATED WITH CHEMOTHERAPY-INDUCED TUMOUR LYSIS IN A PATIENT WITH SMALL-CELL LUNG CARCINOMA. RESPIROL-CASE-REP 2018?6:NO. 3.", "literaturereference_normalized": "successful treatment by tolvaptan of the syndrome of inappropriate antidiuretic hormone secretion that may be associated with chemotherapy induced tumour lysis in a patient with small cell lung carcinoma", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20180405", "receivedate": "20180316", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14650897, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "PHHY2018JP030733", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMLODIPINE BESYLATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPERTENSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMLODIPINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "76959", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL LUNG CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "100 MG/M2, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL LUNG CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE INTRAVENOUS INFUSION" } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hyponatraemia", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "MIYASHITA K, MATSUURA S, NAOI H, TSUKUI M, KOSHIMIZU N, SUDA T. SUCCESSFUL TREATMENT BY TOLVAPTAN OF THE SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION THAT MAY BE ASSOCIATED WITH CHEMOTHERAPY-INDUCED TUMOUR LYSIS IN A PATIENT WITH SMALL-CELL LUNG CARCINOMA. RESPIROLOGY CASE REPORTS. 2018?6 (3):1-3", "literaturereference_normalized": "successful treatment by tolvaptan of the syndrome of inappropriate antidiuretic hormone secretion that may be associated with chemotherapy induced tumour lysis in a patient with small cell lung carcinoma", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20181218", "receivedate": "20180308", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14612168, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190204" }, { "companynumb": "JP-MYLANLABS-2018M1014474", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "091063", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "AUC=5", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL LUNG CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AMLODIPINE BESYLATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPERTENSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMLODIPINE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL LUNG CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tumour lysis syndrome", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "MIYASHITA K, MATSUURA S, NAOI H, TSUKUI M, KOSHIMIZU N, SUDA T. SUCCESSFUL TREATMENT BY TOLVAPTAN OF THE SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION THAT MAY BE ASSOCIATED WITH CHEMOTHERAPY-INDUCED TUMOUR LYSIS IN A PATIENT WITH SMALL-CELL LUNG CARCINOMA.. RESPIROL-CASE-REP. 2018?NO. 3:6", "literaturereference_normalized": "successful treatment by tolvaptan of the syndrome of inappropriate antidiuretic hormone secretion that may be associated with chemotherapy induced tumour lysis in a patient with small cell lung carcinoma", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20180302", "receivedate": "20180302", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14590866, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "JP-SUN PHARMACEUTICAL INDUSTRIES LTD-2018RR-166504", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "77926", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG/M2, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL LUNG CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL LUNG CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." } ], "patientagegroup": null, "patientonsetage": "70", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tumour lysis syndrome", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MIYASHITA K, MATSUURA S, NAOI H, TSUKUI M, KOSHIMIZU N, SUDA T. SUCCESSFUL TREATMENT BY TOLVAPTAN OF THE SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION THAT MAY BE ASSOCIATED WITH CHEMOTHERAPY-INDUCED TUMOUR LYSIS IN A PATIENT WITH SMALL-CELL LUNG CARCINOMA. RESPIROLOGY CASE REPORTS. 2018?6(3):E00296", "literaturereference_normalized": "successful treatment by tolvaptan of the syndrome of inappropriate antidiuretic hormone secretion that may be associated with chemotherapy induced tumour lysis in a patient with small cell lung carcinoma", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20180317", "receivedate": "20180316", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14646800, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" } ]

{ "abstract": "Two female patients aged 88 and 82 who were being treated for constipation with lactulose, developed life-threatening dilatation of the bowel. Both underwent surgery. One of them was found to have cancer of the bowel; she had an uneventful postoperative recovery. No mechanical abnormalities were found in the second patient but she died due to respiratory insufficiency following aspiration. Lactulose is one of the most frequently prescribed laxatives. In the colon it is metabolized by bacteria into short-chain fatty acids, hydrogen and carbon dioxide. The resulting production of gas in the colon can contribute to a non-toxic megacolon, particularly in patients with delayed intestinal passage.", "affiliations": "Afd. Inwendige Geneeskunde, VU Medisch Centrum, De Boelelaan 1117, 1081 HV Amsterdam. jj.vandervliet@vumc.nl", "authors": "van der Vliet|H J|HJ|;van Bodegraven|A A|AA|", "chemical_list": "D005232:Fatty Acids, Volatile; D005765:Gastrointestinal Agents; D002245:Carbon Dioxide; D007792:Lactulose; D006859:Hydrogen", "country": "Netherlands", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0028-2162", "issue": "148(20)", "journal": "Nederlands tijdschrift voor geneeskunde", "keywords": null, "medline_ta": "Ned Tijdschr Geneeskd", "mesh_terms": "D000368:Aged; D000369:Aged, 80 and over; D002245:Carbon Dioxide; D003106:Colon; D003110:Colonic Neoplasms; D003248:Constipation; D017809:Fatal Outcome; D005232:Fatty Acids, Volatile; D005260:Female; D005765:Gastrointestinal Agents; D006801:Humans; D006859:Hydrogen; D007792:Lactulose; D008531:Megacolon; D011015:Pneumonia, Aspiration; D011183:Postoperative Complications; D012131:Respiratory Insufficiency", "nlm_unique_id": "0400770", "other_id": null, "pages": "998-1001", "pmc": null, "pmid": "15181726", "pubdate": "2004-05-15", "publication_types": "D002363:Case Reports; D004740:English Abstract; D016428:Journal Article", "references": null, "title": "Megacolon during treatment with lactulose.", "title_normalized": "megacolon during treatment with lactulose" }

[ { "companynumb": "NL-VISTAPHARM, INC.-VER201801-000308", "fulfillexpeditecriteria": "1", "occurcountry": "NL", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LACTULOSE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "074138", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CONSTIPATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LACTULOSE." } ], "patientagegroup": null, "patientonsetage": "88", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Megacolon", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "VAN DER VLIET H,VAN BODEGRAVEN A. MEGACOLON DURING TREATMENT WITH LACTULOSE. NED TIJDSCHR GENEESKD 2004 MAY 15?148(20):998-1001.", "literaturereference_normalized": "megacolon during treatment with lactulose", "qualification": "1", "reportercountry": "NL" }, "primarysourcecountry": "NL", "receiptdate": "20180226", "receivedate": "20180209", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14508458, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20180509" }, { "companynumb": "NL-VISTAPHARM, INC.-VER201801-000309", "fulfillexpeditecriteria": "1", "occurcountry": "NL", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LACTULOSE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "074138", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CONSTIPATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LACTULOSE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MORPHINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CONSTIPATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MORPHINE" } ], "patientagegroup": null, "patientonsetage": "82", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Aspiration", "reactionmeddraversionpt": "21.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "21.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Megacolon", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Gastrointestinal sounds abnormal", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Intestinal obstruction", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Gastric dilatation", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "VAN DER VLIET H,VAN BODEGRAVEN A. MEGACOLON DURING TREATMENT WITH LACTULOSE. NED TIJDSCHR GENEESKD 2004 MAY 15?148(20):998-1001.", "literaturereference_normalized": "megacolon during treatment with lactulose", "qualification": "1", "reportercountry": "NL" }, "primarysourcecountry": "NL", "receiptdate": "20180226", "receivedate": "20180209", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14508460, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20180509" } ]

{ "abstract": "Richter syndrome represents the transformation of the chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most frequently the diffuse large B-cell lymphoma (DLBCL). In this report we describe a patient with CLL, who developed a clonally-related pleomorphic highly-aggressive mantle cell lymphoma (MCL) after five cycles of a fludarabine-based second-line therapy for the first relapse of CLL. Molecular cytogenetic methods together with whole-exome sequencing revealed numerous gene alterations restricted to the MCL clone (apart from the canonical t(11;14)(q13;q32) translocation) including gain of one copy of ATM gene or emergence of TP53, CREBBP, NUP214, FUBP1 and SF3B1 gene mutations. Similarly, gene expression analysis revealed vast differences between the MCL and CLL transcriptome, including overexpression of cyclin D1, downregulation of cyclins D2 and D3, or downregulation of IL4R in the MCL clone. Backtracking analysis using quantitative PCR specifically detecting an MCL-restricted focal deletion of TP53 revealed that the pre-MCL clone appeared in the bone marrow and peripheral blood of the patient approximately 4 years before the clinical manifestation of MCL. Both molecular cytogenetic and sequencing data support the hypothesis of a slow development of the pre-MCL clone in parallel to CLL over several years, and thereby exclude the possibility that the transformation event occurred at the stage of the CLL relapse clone by mere t(11;14)(q13;q32) acquisition.", "affiliations": "Department of Hematology, Charles University General Hospital Prague, Prague, Czech Republic. pavel.klener@gmail.com.;Childhood Leukemia Investigation Prague (CLIP), Faculty Hospital Motol Prague, Prague, Czech Republic.;Center of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.;Department of Pathology, Charles University General Hospital Prague, Prague, Czech Republic.;Center of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.;Department of Hematology, Charles University General Hospital Prague, Prague, Czech Republic.;Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Faculty Hospital Motol Prague, Prague, Czech Republic.;Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.;Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.;Childhood Leukemia Investigation Prague (CLIP), Faculty Hospital Motol Prague, Prague, Czech Republic.;Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.;Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.;Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.;Center of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.;Center of Oncocytogenetics, Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.;Synlab Genetics, Department of Cytogenetics, Prague, Czech Republic.;Synlab Genetics, Department of Cytogenetics, Prague, Czech Republic.;Department of Hematology, Charles University General Hospital Prague, Prague, Czech Republic.", "authors": "Klener|Pavel|P|;Fronkova|Eva|E|;Berkova|Adela|A|;Jaksa|Radek|R|;Lhotska|Halka|H|;Forsterova|Kristina|K|;Soukup|Jan|J|;Kulvait|Vojtech|V|;Vargova|Jarmila|J|;Fiser|Karel|K|;Prukova|Dana|D|;Alam|Mahmudul|M|;Calvin Lenyeletse Maswabi|Bokang|B|;Michalova|Kyra|K|;Zemanova|Zuzana|Z|;Jancuskova|Tereza|T|;Pekova|Sona|S|;Trneny|Marek|M|", "chemical_list": "D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53", "country": "United States", "delete": false, "doi": "10.1002/ijc.30263", "fulltext": null, "fulltext_license": null, "issn_linking": "0020-7136", "issue": "139(10)", "journal": "International journal of cancer", "keywords": "Richteŕs transformation; chronic lymphocytic leukemia; clonal evolution; mantle cell lymphoma; transforming genes", "medline_ta": "Int J Cancer", "mesh_terms": "D014408:Biomarkers, Tumor; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D019656:Loss of Heterozygosity; D016403:Lymphoma, Large B-Cell, Diffuse; D020522:Lymphoma, Mantle-Cell; D008875:Middle Aged; D014178:Translocation, Genetic; D016159:Tumor Suppressor Protein p53", "nlm_unique_id": "0042124", "other_id": null, "pages": "2252-60", "pmc": null, "pmid": "27407063", "pubdate": "2016-11-15", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Mantle cell lymphoma-variant Richter syndrome: Detailed molecular-cytogenetic and backtracking analysis reveals slow evolution of a pre-MCL clone in parallel with CLL over several years.", "title_normalized": "mantle cell lymphoma variant richter syndrome detailed molecular cytogenetic and backtracking analysis reveals slow evolution of a pre mcl clone in parallel with cll over several years" }

[ { "companynumb": "CZ-ROCHE-2339641", "fulfillexpeditecriteria": "1", "occurcountry": "CZ", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF R-ESHAP CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF R-ESHAP CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "FLUDARABINE PHOSPHATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF FCR CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200503", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUDARABINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF FCR CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200503", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYTARABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF R-ESHAP CHEMOTHERAPY; HIGH-DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ARA-C" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "103705", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF FCR AND R-ESHAP CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200503", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE SODIUM SUCCINATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF R-ESHAP CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SOLU-MEDROL" } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug resistance", "reactionmeddraversionpt": "22.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Richter^s syndrome", "reactionmeddraversionpt": "22.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "KLENER P, FRONKOVA E, BERKOVA A, JAKSA R, LHOTSKA H, FORSTEROVA K, ET AL MANTLE CELL LYMPHOMA-VARIANT RICHTER SYNDROME: DETAILED MOLECULAR-CYTOGENETIC AND BACKTRACKING ANALYSIS REVEALS SLOW EVOLUTION OF A PRE-MCL CLONE IN PARALLEL WITH CLL OVER SEVERAL YEARS. INT-J-CANCER 2016?139(10):2252-2260.", "literaturereference_normalized": "mantle cell lymphoma variant richter syndrome detailed molecular cytogenetic and backtracking analysis reveals slow evolution of a pre mcl clone in parallel with cll over several years", "qualification": "3", "reportercountry": "CZ" }, "primarysourcecountry": "CZ", "receiptdate": "20190621", "receivedate": "20190621", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16461047, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190711" }, { "companynumb": "CZ-TEVA-2019-CZ-1061106", "fulfillexpeditecriteria": "1", "occurcountry": "CZ", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE SODIUM SUCCINATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF R-ESHAP CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SOLU-MEDROL" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF FCR CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200503", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF FCR AND R-ESHAP CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200503", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "FLUDARABINE PHOSPHATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "078610", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF FCR CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200503", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUDARABINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF R-ESHAP CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF R-ESHAP CHEMOTHERAPY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYTARABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "PART OF R-ESHAP CHEMOTHERAPY; HIGH-DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ARA-C" } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Richter^s syndrome", "reactionmeddraversionpt": "22.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Drug resistance", "reactionmeddraversionpt": "22.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "KLENER P, FRONKOVA E, BERKOVA A, JAKSA R, LHOTSKA H, FORSTEROVA K, ET AL. MANTLE CELL LYMPHOMA-VARIANT RICHTER SYNDROME: DETAILED MOLECULAR-CYTOGENETIC AND BACKTRACKING ANALYSIS REVEALS SLOW EVOLUTION OF A PRE-MCL CLONE IN PARALLEL WITH CLL OVER SEVERAL YEARS. INT-J-CANCER 2016?139(10):2252-2260.", "literaturereference_normalized": "mantle cell lymphoma variant richter syndrome detailed molecular cytogenetic and backtracking analysis reveals slow evolution of a pre mcl clone in parallel with cll over several years", "qualification": "3", "reportercountry": "CZ" }, "primarysourcecountry": "CZ", "receiptdate": "20190612", "receivedate": "20190612", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16418920, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190711" } ]

{ "abstract": "A 51-year-old Japanese woman developed candidemia as an outpatient secondary to a Candida albicans upper urinary tract infection complicated by previously undiagnosed type 2 diabetes mellitus with poor glycemic control and ureterolithiasis. The patient did not have any risk factors typically associated with candidemia, such as an indwelling vascular catheter, parenteral nutrition or broad-spectrum antibiotic use. During the clinical course, her condition was complicated by unilateral candida endophthalmitis, which progressed despite the administration of systemic antifungal agents and ultimately required vitreous surgery. The etiology of candidemia in this patient and the reason she developed progressive ocular symptoms after starting antifungal treatment are reviewed.", "affiliations": "Division of General Medicine, Department of Comprehensive Medicine 1, Saitama Medical Center, Jichi Medical University, Japan.", "authors": "Suzuki|Reina|R|;Kuroda|Hitoshi|H|;Matsubayashi|Hiroshi|H|;Ishii|Akira|A|;Toyoda|Fumihiko|F|;Kawarai Lefor|Alan|A|;Sugawara|Hitoshi|H|", "chemical_list": "D000935:Antifungal Agents; D001786:Blood Glucose", "country": "Japan", "delete": false, "doi": "10.2169/internalmedicine.54.4691", "fulltext": null, "fulltext_license": null, "issn_linking": "0918-2918", "issue": "54(20)", "journal": "Internal medicine (Tokyo, Japan)", "keywords": null, "medline_ta": "Intern Med", "mesh_terms": "D000935:Antifungal Agents; D001786:Blood Glucose; D002176:Candida albicans; D058387:Candidemia; D003924:Diabetes Mellitus, Type 2; D009877:Endophthalmitis; D005260:Female; D006801:Humans; D008875:Middle Aged; D010289:Parenteral Nutrition, Total; D012307:Risk Factors; D053039:Ureterolithiasis; D014552:Urinary Tract Infections", "nlm_unique_id": "9204241", "other_id": null, "pages": "2693-8", "pmc": null, "pmid": "26466713", "pubdate": "2015", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Candidemia from an upper urinary tract infection complicated by candida endophthalmitis.", "title_normalized": "candidemia from an upper urinary tract infection complicated by candida endophthalmitis" }

[ { "companynumb": "JP-LUPIN PHARMACEUTICALS INC.-2015-03805", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "065125", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "BACTERIAL INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LEVOFLOXACIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "078424", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "BACTERIAL INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVOFLOXACIN." } ], "patientagegroup": null, "patientonsetage": "51", "patientonsetageunit": "801", "patientsex": "2", "patientweight": "75", "reaction": [ { "reactionmeddrapt": "Systemic candida", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Candida endophthalmitis", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "SUGAWARA H, SUZUKI R, KURODA H, MATSUBAYASHI H, ISHII A, TOYODA F, LEFOR A. CANDIDEMIA FROM AN UPPER URINARY TRACT INFECTION COMPLICATED BY CANDIDA ENDOPHTHALMITIS. INTERNAL MEDICINE. 2015?54:2693-2698.", "literaturereference_normalized": "candidemia from an upper urinary tract infection complicated by candida endophthalmitis", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20151127", "receivedate": "20151127", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 11782617, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160305" }, { "companynumb": "JP-TEVA-611535ISR", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEVOFLOXACIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "076361", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM DAILY; 2 DAYS BEFORE ADMISSION", "drugenddate": null, "drugenddateformat": null, "drugindication": "BACTERIAL INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVOFLOXACIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." } ], "patientagegroup": null, "patientonsetage": "51", "patientonsetageunit": "801", "patientsex": "2", "patientweight": "75", "reaction": [ { "reactionmeddrapt": "Candida endophthalmitis", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Systemic candida", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "SUZUKI R, KURODA H, MATSUBAYASHI H, ISHII A, TOYODA F, LEFOR AK, ET AL. CANDIDEMIA FROM AN UPPER URINARY TRACT INFECTION COMPLICATED BY CANDIDA ENDOPHTHALMITIS. INTERN-MED 2015? 54(20):2693-2698.", "literaturereference_normalized": "candidemia from an upper urinary tract infection complicated by candida endophthalmitis", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20151125", "receivedate": "20151125", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11779829, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20160304" } ]

{ "abstract": "Clinical impact of imatinib was evaluated in 20 patients (median age, 37 years; range, 15-67 years) with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), who were administered with induction chemotherapy of daunorubicin, vincristine, prednisolone, and L-asparaginase, along with imatinib 600 mg/day during remission induction and 400 mg/day during consolidation courses. One patient died on day 14 from septic shock, while the remaining 19 achieved complete remission (CR). In total, 15 patients underwent allogeneic hematopoietic cell transplantation (HCT) during first CR. After median follow-up period of 799 days, six patients experienced recurrence; two with early recurrence within 100 days, one with leptomeningeal recurrence at 11 month, and three with post-HCT recurrence. Eight patients died. Median CR duration (821 days) and median patient survival (894 days) in the study were significantly longer by 2.9- and 2.3-fold, respectively, when compared to those of 18 historical patients treated with same regimen of combination chemotherapy without imatinib. Toxicities of the combined treatment were manageable and included grade 4 myelosuppression (n = 20) and reversible > or = grade 3 hyperbilirubinemia (n = 4). Beneficial clinical effects were observed when imatinib was added to combination chemotherapy in patients with newly diagnosed Ph+ ALL. Further studies with larger number of patients are necessary.", "affiliations": "Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea.", "authors": "Lee|K-H|KH|;Lee|J-H|JH|;Choi|S-J|SJ|;Lee|J-H|JH|;Seol|M|M|;Lee|Y-S|YS|;Kim|W-K|WK|;Lee|J-S|JS|;Seo|E-J|EJ|;Jang|S|S|;Park|C-J|CJ|;Chi|H-S|HS|", "chemical_list": "D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate", "country": "England", "delete": false, "doi": "10.1038/sj.leu.2403886", "fulltext": null, "fulltext_license": null, "issn_linking": "0887-6924", "issue": "19(9)", "journal": "Leukemia", "keywords": null, "medline_ta": "Leukemia", "mesh_terms": "D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001549:Benzamides; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011446:Prospective Studies; D011743:Pyrimidines; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016896:Treatment Outcome", "nlm_unique_id": "8704895", "other_id": null, "pages": "1509-16", "pmc": null, "pmid": "16034462", "pubdate": "2005-09", "publication_types": "D016430:Clinical Trial; D003160:Comparative Study; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't", "references": null, "title": "Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.", "title_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia" }

[ { "companynumb": "KR-PFIZER INC-2018150061", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4000 U/M^2, CYCLIC (DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, CYCLIC (SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" } ], "patientagegroup": null, "patientonsetage": "54", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180417", "receivedate": "20180417", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14769284, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150051", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "(4000 U/M2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" } ], "patientagegroup": null, "patientonsetage": "32", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14759014, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150048", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4000 IU/M2, CYCLIC (ON DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" } ], "patientagegroup": null, "patientonsetage": "28", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14759007, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150063", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, SIX DOSES", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4000 U/M2, CYCLIC (DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14758997, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018149375", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4000 U/M2 DAYS 17-28", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" } ], "patientagegroup": null, "patientonsetage": "25", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14759328, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150052", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, (SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, CYCLIC(4000 U/M^2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY FOR 14 DAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." } ], "patientagegroup": null, "patientonsetage": "30", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180417", "receivedate": "20180417", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14770026, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150064", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, CYCLIC(4000 U/M^2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY, FOR 14 DAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." } ], "patientagegroup": null, "patientonsetage": "21", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180417", "receivedate": "20180417", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14770896, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150056", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, CYCLIC(4000 U/M^2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" } ], "patientagegroup": null, "patientonsetage": "34", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14758999, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150062", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, CYCLIC(4000 U/M^2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" } ], "patientagegroup": null, "patientonsetage": "27", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14759009, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150053", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "CYCLIC(4000 U/M^2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "L-ASPARAGINASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." } ], "patientagegroup": null, "patientonsetage": "19", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14759002, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150049", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK((SIX DOSES))", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, CYCLIC(4000 U/M^2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." } ], "patientagegroup": null, "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14759012, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150047", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, CYCLIC(4000 U/M^2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." } ], "patientagegroup": null, "patientonsetage": "28", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14759010, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150058", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, CYCLIC(4000 U/M^2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" } ], "patientagegroup": null, "patientonsetage": "67", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14759000, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150046", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, CYCLIC(4000 U/M^2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY, FOR 14 DAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" } ], "patientagegroup": null, "patientonsetage": "48", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180417", "receivedate": "20180417", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14769315, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150059", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, UNK(SIX DOSES)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, CYCLIC(4000 U/M^2)(DAYS 17-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" } ], "patientagegroup": null, "patientonsetage": "44", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14759001, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "KR-PFIZER INC-2018150057", "fulfillexpeditecriteria": "1", "occurcountry": "KR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GLEEVEC" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DAUNORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON DAYS 1-3)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DAUNORUBICIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12 MG/M2, SIX DOSES", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG/M2, CYCLIC (ON DAYS 1-28)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "071484", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 MG, CYCLIC (ON DAYS 1, 8, 15, AND 22)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE SULFATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPARAGINASE" }, "drugadditional": "3", "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4000 U/M22, DAYS 17-28", "drugenddate": null, "drugenddateformat": null, "drugindication": "ACUTE LYMPHOCYTIC LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUNASE" } ], "patientagegroup": null, "patientonsetage": "38", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LEE, K.. CLINICAL EFFECT OF IMATINIB ADDED TO INTENSIVE COMBINATION CHEMOTHERAPY FOR NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA. LEUKEMIA. 2005?19 (9):1509-1516", "literaturereference_normalized": "clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed philadelphia chromosome positive acute lymphoblastic leukemia", "qualification": "3", "reportercountry": "KR" }, "primarysourcecountry": "KR", "receiptdate": "20180413", "receivedate": "20180413", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 14759011, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" } ]

{ "abstract": "Histoplasmosis is a fungal infection caused by a dimorphic fungus, Histoplasma capsulatum. We report a first case of disseminated histoplasmosis in a 34-year-old woman, infected with human immunodeficiency virus (HIV), originating from Ivory Coast and living in Tunisia for 4 years. She was complaining from fever, chronic diarrhoea and pancytopenia. The Histoplasma capsulatum var. capsulatum was identified by direct microscopic examination of the bone marrow. She was treated by Amphotericin B, relayed by itraconazole. Even though a regression of symptoms and normalization of blood cell count (BCC), the patient died in a respiratory distress related to CMV hypoxemic pneumonia.", "affiliations": "Laboratory of Parasitology-Mycology, Rabta Hospital, Jabbari street, 1007 Tunis, Tunisia; Infectious diseases ward, Rabta Hospital, Tunis, Tunisia.;Infectious diseases ward, Rabta Hospital, Tunis, Tunisia; Université de Tunis El Manar, faculté de médecine de Tunis, Tunis, Tunisia.;Infectious diseases ward, Rabta Hospital, Tunis, Tunisia; Université de Tunis El Manar, faculté de médecine de Tunis, Tunis, Tunisia.;Laboratory of Parasitology-Mycology, Rabta Hospital, Jabbari street, 1007 Tunis, Tunisia; Université de Tunis El Manar, faculté de médecine de Tunis, Tunis, Tunisia.;Laboratory of Parasitology-Mycology, Rabta Hospital, Jabbari street, 1007 Tunis, Tunisia; Université de Tunis El Manar, faculté de médecine de Tunis, Tunis, Tunisia.;Laboratory of Parasitology-Mycology, Rabta Hospital, Jabbari street, 1007 Tunis, Tunisia; Université de Tunis El Manar, faculté de médecine de Tunis, Tunis, Tunisia.;Laboratory of Hematology, Rabta Hospital, Tunis, Tunisia; Université de Tunis El Manar, faculté de médecine de Tunis, Tunis, Tunisia.;Infectious diseases ward, Rabta Hospital, Tunis, Tunisia; Université de Tunis El Manar, faculté de médecine de Tunis, Tunis, Tunisia.;Laboratory of Parasitology-Mycology, Rabta Hospital, Jabbari street, 1007 Tunis, Tunisia; Université de Tunis El Manar, faculté de médecine de Tunis, Tunis, Tunisia.", "authors": "Fakhfakh|N|N|;Abdelmlak|R|R|;Aissa|S|S|;Kallel|A|A|;Boudawara|Y|Y|;Bel Hadj|S|S|;Ben Romdhane|N|N|;Touiri Ben Aissa|H|H|;Kallel|K|K|", "chemical_list": "D000935:Antifungal Agents; D017964:Itraconazole; D000666:Amphotericin B", "country": "France", "delete": false, "doi": "10.1016/j.mycmed.2018.02.008", "fulltext": null, "fulltext_license": null, "issn_linking": "1156-5233", "issue": "28(1)", "journal": "Journal de mycologie medicale", "keywords": "Disseminated histoplasmosis; HIV-seropositive patient; Histoplasma capsulatum var. capsulatum; Imported case; Tunisia", "medline_ta": "J Mycol Med", "mesh_terms": "D017088:AIDS-Related Opportunistic Infections; D000328:Adult; D000666:Amphotericin B; D000935:Antifungal Agents; D001853:Bone Marrow; D000076263:Communicable Diseases, Imported; D007560:Cote d'Ivoire; D017809:Fatal Outcome; D005260:Female; D015658:HIV Infections; D006658:Histoplasma; D006660:Histoplasmosis; D006801:Humans; D017964:Itraconazole; D008853:Microscopy; D012128:Respiratory Distress Syndrome; D014416:Tunisia", "nlm_unique_id": "9425651", "other_id": null, "pages": "211-214", "pmc": null, "pmid": "29519625", "pubdate": "2018-03", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Disseminated histoplasmosis diagnosed in the bone marrow of an HIV-infected patient: First case imported in Tunisia.", "title_normalized": "disseminated histoplasmosis diagnosed in the bone marrow of an hiv infected patient first case imported in tunisia" }

[ { "companynumb": "TN-ACCORD-067396", "fulfillexpeditecriteria": "1", "occurcountry": "TN", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "ITRACONAZOLE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "205991", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "HISTOPLASMOSIS DISSEMINATED", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ITRACONAZOLE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "EFAVIRENZ" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EFAVIRENZ." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "LONG DURATION", "drugenddate": null, "drugenddateformat": null, "drugindication": "CEREBRAL TOXOPLASMOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": "6", "activesubstance": null, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CEREBRAL TOXOPLASMOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRIMETHAMINE/PYRIMETHAMINE BITARTRATE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DISSEMINATED TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPICIN" }, { "actiondrug": "6", "activesubstance": null, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CEREBRAL TOXOPLASMOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SULFADIAZINE/SULFADIAZINE SILVER/SULFADIAZINE SODIUM" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DISSEMINATED TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "PYRAZINAMIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DISSEMINATED TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRAZINAMIDE." }, { "actiondrug": "6", "activesubstance": null, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EMTRICITABINE/TENOFOVIR" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DISSEMINATED TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "6", "activesubstance": null, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DISSEMINATED TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ISONIAZID/ISONIAZID CALCIUM PYRUVINATE/ISONIAZID SODIUM GLUCURONATE" } ], "patientagegroup": null, "patientonsetage": "34", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Treatment failure", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "FAKHFAKH N, ABDELMLAK R, AISSA S, KALLEL A, BOUDAWARA Y, BEL HADJ S ET AL. DISSEMINATED HISTOPLASMOSIS DIAGNOSED IN THE BONE MARROW OF AN HIV-INFECTED PATIENT: FIRST CASE IMPORTED IN TUNISIA. JOURNAL DE MYCOLOGIE MEDICALE. 2018? 28(1): 211-214. DOI: HTTPS://DOI.ORG/10.1016/J.MYCMED.2018.02.008", "literaturereference_normalized": "disseminated histoplasmosis diagnosed in the bone marrow of an hiv infected patient first case imported in tunisia", "qualification": "3", "reportercountry": "TN" }, "primarysourcecountry": "TN", "receiptdate": "20180529", "receivedate": "20180529", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14945535, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "TN-BAUSCH-BL-2018-014378", "fulfillexpeditecriteria": "1", "occurcountry": "TN", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PYRAZINAMIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DISSEMINATED TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRAZINAMIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DISSEMINATED TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ITRACONAZOLE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HISTOPLASMOSIS DISSEMINATED", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ITRACONAZOLE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "EFAVIRENZ" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EFAVIRENZ." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "PYRIMETHAMINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CEREBRAL TOXOPLASMOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRIMETHAMINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "40069", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "LONG DURATION", "drugenddate": null, "drugenddateformat": null, "drugindication": "CEREBRAL TOXOPLASMOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DISSEMINATED TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DISSEMINATED TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPICIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "EMTRICITABINE\\TENOFOVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EMTRICITABINE, TENOFOVIR" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ISONIAZID" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DISSEMINATED TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ISONIAZID." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "SULFADIAZINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CEREBRAL TOXOPLASMOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SULFADIAZINE." } ], "patientagegroup": null, "patientonsetage": "34", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cytomegalovirus infection", "reactionmeddraversionpt": "21.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Pneumonia cytomegaloviral", "reactionmeddraversionpt": "21.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Hypoxia", "reactionmeddraversionpt": "21.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "FAKHFAKH N, ABDELMLAK R, AISSA S, KALLEL A, BOUDAWARA Y, BEL HADJ S. DISSEMINATED HISTOPLASMOSIS DIAGNOSED IN THE BONE MARROW OF AN HIV-INFECTED PATIENT: FIRST CASE IMPORTED IN TUNISIA. JOURNAL DE MYCOLOGIE MEDICALE. 2018?28(1):211-214.", "literaturereference_normalized": "disseminated histoplasmosis diagnosed in the bone marrow of an hiv infected patient first case imported in tunisia", "qualification": "1", "reportercountry": "TN" }, "primarysourcecountry": "TN", "receiptdate": "20180523", "receivedate": "20180523", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14930245, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "TN-ALEMBIC PHARMACUETICALS LIMITED-2018SCAL000357", "fulfillexpeditecriteria": "1", "occurcountry": "TN", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "SULFADIAZINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CEREBRAL TOXOPLASMOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SULFADIAZIN" }, { "actiondrug": null, "activesubstance": null, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EMTRICITABIN TENOFOVIR" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ITRACONAZOLE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "206741", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "HISTOPLASMOSIS DISSEMINATED", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ITRACONAZOLE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "RIFAMPIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIFAMPICIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ISONIAZID" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ISONIAZID." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "GANCICLOVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM/KILOGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "PNEUMONIA CYTOMEGALOVIRAL", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GANCICLOVIR." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CEREBRAL TOXOPLASMOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASON /00016001/" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PYRAZINAMIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRAZINAMID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXON" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "EFAVIRENZ" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EFAVIRENZ." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETHAMBUTOL HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "TUBERCULOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETHAMBUTOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PYRIMETHAMINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CEREBRAL TOXOPLASMOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PYRIMETHAMINE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Treatment failure", "reactionmeddraversionpt": "21.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "FAKHFAKH N, ABDELMLAK R, AISSA S, KALLEL A, BOUDAWARA Y, BEL HADJ S. DISSEMINATED HISTOPLASMOSIS DIAGNOSED IN THE BONE MARROW OF AN HIV-INFECTED PATIENT: FIRST CASE IMPORTED IN TUNISIA. JOURNAL DE MYCOLOGIE MEDICALE. 2018?28 (1):211-214", "literaturereference_normalized": "disseminated histoplasmosis diagnosed in the bone marrow of an hiv infected patient first case imported in tunisia", "qualification": "3", "reportercountry": "TN" }, "primarysourcecountry": "TN", "receiptdate": "20180522", "receivedate": "20180522", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14923461, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" } ]

{ "abstract": "In this case report of a patient with angioimmunoblastic T-cell lymphoma (AITL), we describe the occurrence of three sequential complications that have been reported uncommonly in this disease subtype. Firstly, the patient developed hypercalcemia due to elevated 1,25-didydroxyvitamin D. Although hypercalcemia in AITL is not rare (1-2% incidence), this case was unusual in that the complication developed when disease appeared stable and symptomatically, he was doing well otherwise. Hypercalcemia surprisingly resolved a few months later at a time when his disease appeared to be progressing. A year later, the patient presented with digital ischemia necessitating partial amputation of a finger. Pathological exam revealed granulomatous vasculitis of small and medium arterioles with infiltrating malignant T lymphocytes. Although skin manifestations are common in AITL, necrotizing granulomatous vasculitis with accompanying tumor cells leading to severe digital ischemia appears rare. Subsequently the patient developed profound pancytopenia with bone marrow confirming severe aplastic anemia. To our knowledge only one other case of aplastic anemia has been reported in a patient with AITL. We discuss the diagnostic and management considerations involved in this patient care and review similar reported cases.", "affiliations": "Texas Tech University Health Sciences Center, Lubbock, Texas USA.;Texas Tech University Health Sciences Center, Lubbock, Texas USA. Electronic address: jonathan.kopel@ttuhsc.edu.;Texas Tech University Health Sciences Center, Lubbock, Texas USA.;Internal Medicine and Hematology-Oncology, Covenant Health System, Lubbock, Texas USA.;University Medical Center, Lubbock, Texas USA.;Department of Pathology, Covenant Health System, Lubbock, Texas USA.;Texas Tech University Health Sciences Center, Lubbock, Texas USA; Internal Medicine and Hematology-Oncology, Covenant Health System, Lubbock, Texas USA.", "authors": "Swarup|Sriman|S|;Kopel|Jonathan|J|;Thein|Kyaw Zin|KZ|;Tarafdar|Kaiser|K|;Swarup|Khatrina|K|;Thirumala|Seshadri|S|;Quick|Donald P|DP|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1016/j.amjms.2020.09.003", "fulltext": null, "fulltext_license": null, "issn_linking": "0002-9629", "issue": "361(3)", "journal": "The American journal of the medical sciences", "keywords": "1,25-dihydroxyvitamin D; Angioimmunoblastic T-Cell Lymphoma (AITL); Aplastic anemia; Digital ischemia; Granulomatous vasculitis; Hypercalcemia", "medline_ta": "Am J Med Sci", "mesh_terms": "D000741:Anemia, Aplastic; D006801:Humans; D006934:Hypercalcemia; D007119:Immunoblastic Lymphadenopathy; D016399:Lymphoma, T-Cell; D008297:Male; D008875:Middle Aged; D014657:Vasculitis", "nlm_unique_id": "0370506", "other_id": null, "pages": "375-382", "pmc": null, "pmid": "33097193", "pubdate": "2021-03", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Sequential Complications of Hypercalcemia, Necrotizing Granulomatous Vasculitis, and Aplastic Anemia Occurring in One Patient with Angioimmunoblastic T-cell Lymphoma.", "title_normalized": "sequential complications of hypercalcemia necrotizing granulomatous vasculitis and aplastic anemia occurring in one patient with angioimmunoblastic t cell lymphoma" }

[ { "companynumb": "US-SAGENT PHARMACEUTICALS-2021SAG002198", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "DOXORUBICIN HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "091495", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, Q3W", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXORUBICIN HYDROCHLORIDE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, Q3W", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "VINCRISTINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, Q3W", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, Q3W", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, Q3W", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE" } ], "patientagegroup": null, "patientonsetage": "58", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Weight decreased", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Myelosuppression", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Decreased appetite", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Asthenia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Swarup S, Kopel J, Thein KZ, Tarafdar K, Swarup K, Thirumala S, et al.. Sequential Complications of Hypercalcemia, Necrotizing Granulomatous Vasculitis, and Aplastic Anemia Occurring in One Patient with Angioimmunoblastic T-cell Lymphoma. Am-J-Med-Sci. 2021;361(3):275-382", "literaturereference_normalized": "sequential complications of hypercalcemia necrotizing granulomatous vasculitis and aplastic anemia occurring in one patient with angioimmunoblastic t cell lymphoma", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211012", "receivedate": "20211012", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19948698, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "US-TEVA-2021-US-1961086", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "74656", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 MG/M2 ON DAY 1 ONCE IN EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DOXORUBICIN" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "63097", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXORUBICIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "74284", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "079160", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG/M2 ON DAY 1 AND DAY 8, ONCE IN 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "080356", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MG/KG DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "080356", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "Granulomatosis with polyangiitis", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "080356", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "AT MODERATE DOSES (MEAN DOSE 0.5 MG/KG/DAY).", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "080356", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "VINCRISTINE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "75493", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "4", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40MG ON DAY 1, ONCE IN 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CALCITONIN" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Hypercalcaemia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CALCITONIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ZOLEDRONIC ACID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Hypercalcaemia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZOLEDRONIC ACID" } ], "patientagegroup": "5", "patientonsetage": "58", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Asthenia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Decreased appetite", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Weight decreased", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Myelosuppression", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cytopenia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "Swarup S, Kopel J, Thein KZ, Tarafdar K, Swarup K, Thirumala S, et al. Sequential Complications of Hypercalcemia, Necrotizing Granulomatous Vasculitis, and Aplastic Anemia Occurring in One Patient with Angioimmunoblastic T-cell Lymphoma. Am-J-Med-Sci 2021;361(3):375-382.", "literaturereference_normalized": "sequential complications of hypercalcemia necrotizing granulomatous vasculitis and aplastic anemia occurring in one patient with angioimmunoblastic t cell lymphoma", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211019", "receivedate": "20211007", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19931568, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "US-FRESENIUS KABI-FK202110417", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "074983", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "CHOP?ETOPOSIDE EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA STAGE IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE (MANUFACTURER UNKNOWN)" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN,UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "CHOP?ETOPOSIDE EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "CHOP?ETOPOSIDE EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA STAGE IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "VINCRISTINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "CHOP?ETOPOSIDE EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA STAGE IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DOXORUBICIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "063277", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "CHOP?ETOPOSIDE EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA STAGE IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXORUBICIN (MANUFACTURER UNKNOWN)" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN,UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "1 MG/KG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA STAGE IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." } ], "patientagegroup": null, "patientonsetage": "58", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Decreased appetite", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Weight decreased", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Asthenia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SWARUP S, KOPEL J, THEIN K, TARAFDAR K, SWARUP K, THIRUMALA S. SEQUENTIAL COMPLICATIONS OF HYPERCALCEMIA, NECROTIZING GRANULOMATOUS VASCULITIS, AND APLASTIC ANEMIA OCCURRING IN ONE PATIENT WITH ANGIOIMMUNOBLASTIC T?CELL LYMPHOMA. AMERICAN JOURNAL OF THE MEDICAL SCIENCES. 2021 MAR?361 (3):375?382.", "literaturereference_normalized": "sequential complications of hypercalcemia necrotizing granulomatous vasculitis and aplastic anemia occurring in one patient with angioimmunoblastic t cell lymphoma", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210930", "receivedate": "20210930", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19902132, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "US-HIKMA PHARMACEUTICALS USA INC.-US-H14001-20-05325", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "CALCITONIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CALCITONIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ZOLEDRONIC ACID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZOLEDRONIC ACID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "074290", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHEMOTHERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHEMOTHERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOXORUBICIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "062975", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHEMOTHERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXORUBICIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CHEMOTHERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "080352", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "080352", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CHEMOTHERAPY", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "VINCRISTINE SULFATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHEMOTHERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ONCOVIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CHEMOTHERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "084610", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CHEMOTHERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." } ], "patientagegroup": null, "patientonsetage": "58", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Asthenia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Decreased appetite", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug intolerance", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Weight decreased", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Myelosuppression", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "SWARUP S, KOPEL J, THEIN K, TARAFDAR K, SWARUP K, THIRUMALA S, QUICK D. SEQUENTIAL COMPLICATIONS OF HYPERCALCEMIA, NECROTIZING GRANULOMATOUS VASCULITIS, AND APLASTIC ANEMIA OCCURRING IN ONE PATIENT WITH ANGIOIMMUNOBLASTIC T?CELL LYMPHOMA. AMERICAN JOURNAL OF THE MEDICAL SCIENCES. 2021 MAR 01?361:3:375?382.", "literaturereference_normalized": "sequential complications of hypercalcemia necrotizing granulomatous vasculitis and aplastic anemia occurring in one patient with angioimmunoblastic t cell lymphoma", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20210917", "receivedate": "20201127", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18554381, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "US-STRIDES ARCOLAB LIMITED-2021SP028147", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "210785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MILLIGRAM/KILOGRAM PER DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "210785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "AS PART OF CHOP-ETOPOSIDE REGIMEN; EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Granulomatosis with polyangiitis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "210785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MILLIGRAM/KILOGRAM PER DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "210785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "GRADUALLY TAPERED PERIODICALLY OVER WEEKS TO 20 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "210785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "AT MODERATE DOSES (MEAN DOSE 0.5 MG/KG/DAY)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "210785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOXORUBICIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "CHOP-ETOPOSIDE REGIMEN;EVERY 3 WEEKS EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXORUBICIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "75 MILLIGRAM/SQ. METER, EVERY 3 WEEKS (ON DAY 1)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "75", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "CHOP-ETOPOSIDE REGIMEN, EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "VINCRISTINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "CHOP-ETOPOSIDE REGIMEN; EVERY 3 WEEKS, EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GEMCITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MILLIGRAM/SQ. METER, EVERY 3 WEEKS (ON DAY 1 AND DAY 8)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GEMCITABINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MILLIGRAM, EVERY 3 WEEKS (ON DAY 1)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "CHOP-ETOPOSIDE REGIMEN; EVERY 3 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "Angioimmunoblastic T-cell lymphoma stage IV", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CALCITONIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Hypercalcaemia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CALCITONIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ZOLEDRONIC ACID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Hypercalcaemia", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZOLEDRONIC ACID" } ], "patientagegroup": null, "patientonsetage": "58", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cytopenia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Myelosuppression", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Asthenia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Decreased appetite", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Weight decreased", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug intolerance", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Therapeutic response decreased", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Swarup S, Kopel J, Thein KZ, Tarafdar K, Swarup K, Thirumala S, et al.. Sequential Complications of Hypercalcemia, Necrotizing Granulomatous Vasculitis, and Aplastic Anemia Occurring in One Patient with Angioimmunoblastic T-cell Lymphoma.. Am-J-Med-Sci. 2021;361(3):375-382", "literaturereference_normalized": "sequential complications of hypercalcemia necrotizing granulomatous vasculitis and aplastic anemia occurring in one patient with angioimmunoblastic t cell lymphoma", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20211001", "receivedate": "20211001", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19904033, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" } ]

{ "abstract": "We report 2 cases of composite lymphoma comprising mantle cell lymphoma and peripheral T-cell lymphoma, not otherwise specified, a rare association that has only been reported twice in the literature. In case 1, a 64-year-old woman presented with massive splenomegaly and lymphadenopathy. Immunohistochemical studies of the lymph node biopsy suggested the presence of 2 lymphomas, a predominant component of a peripheral T-cell lymphoma, not otherwise specified and an in situ mantle cell neoplasia. These suspicions were confirmed with polymerase chain reaction and fluorescence in situ hybridization studies. In case 2, a 45-year-old man presented with an enlarged right tonsil. Contrary to case 1, the biopsy suggested a predominant infiltration of a classical mantle cell lymphoma and an atypical proliferation of T cells. Biclonality was also confirmed with fluorescence in situ hybridization and molecular techniques. Both cases were treated with an up-front autologous stem cell transplantation after achieving first complete remission, and they remained free of disease for a long period of time.", "affiliations": "Departments of Hematology.;Departments of Pathology.;Hematology, Universitary Gregorio Marañón Hospital.;Pathology, Universitary Infanta Leonor Hospital.;Hematology, Universitary Gregorio Marañón Hospital.;Departments of Pathology.;Departments of Hematology.;Hematology, Universitary Gregorio Marañón Hospital.;Departments of Hematology.", "authors": "González-Gascón Y Marín|Isabel|I|;Menarguez|Javier|J|;Kwon|Mi|M|;Burdaspal|Ana|A|;Martínez-Laperche|Carolina|C|;Castro|Yolanda|Y|;Infante|María Stefania|MS|;Díez-Martín|José-Luis|JL|;Hernández-Rivas|José-Ángel|JÁ|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1097/PAI.0000000000000769", "fulltext": null, "fulltext_license": null, "issn_linking": "1533-4058", "issue": "28(10)", "journal": "Applied immunohistochemistry & molecular morphology : AIMM", "keywords": null, "medline_ta": "Appl Immunohistochem Mol Morphol", "mesh_terms": "D002999:Clone Cells; D058617:Composite Lymphoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes; D020522:Lymphoma, Mantle-Cell; D016411:Lymphoma, T-Cell, Peripheral; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012074:Remission Induction; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous", "nlm_unique_id": "100888796", "other_id": null, "pages": "e94-e98", "pmc": null, "pmid": "30973352", "pubdate": "2020", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Composite Lymphoma Containing Mantle Cell and Peripheral T-cell Lymphoma, Not Otherwise Specified: A Report of 2 Cases Treated With Up-front Autologous Stem Cell Transplantation.", "title_normalized": "composite lymphoma containing mantle cell and peripheral t cell lymphoma not otherwise specified a report of 2 cases treated with up front autologous stem cell transplantation" }

[ { "companynumb": "ES-BAUSCH-BL-2019-065181", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "IBRUTINIB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBRUTINIB" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VINCRISTINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RITUXIMAB" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITUXIMAB." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "40070", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DOXORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXORUBICIN" } ], "patientagegroup": null, "patientonsetage": "64", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Infection", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GONZALEZ-GASCON Y, MENARGUEZ J, KWON M, BURDASPAL A, MARTINEZ- LAPERCHE C, CASTRO Y, INFANTE M, DIEZ-MARTIN J, HERNANDEZ RIVAS J. COMPOSITE LYMPHOMA CONTAINING MANTLE CELL AND PERIPHERAL T -CELL LYMPHOMA, NOT OTHERWISE SPECIFIED: A REPORT OF 2 CASES TREATED WITH UP-FRONT AUTOLOGOUS STEM CELL TRANSPLANTATION. HEMASPHERE. 2019 JUN?3 (S1):836.", "literaturereference_normalized": "composite lymphoma containing mantle cell and peripheral t cell lymphoma not otherwise specified a report of 2 cases treated with up front autologous stem cell transplantation", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20191224", "receivedate": "20191216", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17160514, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200122" }, { "companynumb": "ES-PFIZER INC-2019549599", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "IBRUTINIB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBRUTINIB" } ], "patientagegroup": null, "patientonsetage": "64", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Infection", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GONZALEZ-GASCON, Y.. COMPOSITE LYMPHOMA CONTAINING MANTLE CELL AND PERIPHERAL T -CELL LYMPHOMA, NOT OTHERWISE SPECIFIED: A REPORT OF 2 CASES TREATED WITH UP-FRONT AUTOLOGOUS STEM CELL TRANSPLANTATION. HEMASPHERE. 2019?JUN?3 (S1):836-", "literaturereference_normalized": "composite lymphoma containing mantle cell and peripheral t cell lymphoma not otherwise specified a report of 2 cases treated with up front autologous stem cell transplantation", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20200103", "receivedate": "20191226", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17201764, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200409" } ]

{ "abstract": "This study evaluated pregnancy outcome in women with a prosthetic heart valve, especially with the oral anticoagulation therapy that must be weighed against the risk of intracardiac thrombosis.\n\n\n\nThis multicenter, retrospective, cohort study was undertaken between January 2012 and June 2017. The principal maternal outcome variables included bleeding and thromboembolic complications, infective endocarditis, prosthetic valve thrombosis and heart failure. However, the main foetal outcome variables included miscarriage, mortality, preterm baby, warfarin embryopathy, low birthweight and the mode of delivery.\n\n\n\nA total of 265 pregnancies in women with prosthetic heart valves were evaluated in two groups: Group I (n = 182) covers a mechanical valve, while Group II (n = 82) covers a bioprosthetic valve. The mean age of the patients was 25.2 ± 2.5 years and 24.5 ± 5.2 years in Group I and Group II, respectively. Approximately 80% of the patients had normal echocardiography findings. However, Group I (mechanical prostheses) has a higher incidence (11.54%) of thrombus formation in comparison with the bioprostheses. Hemorrhagic complications and spontaneous miscarriage were statistically significant (p⩽0.05) between the study groups. However, normal pregnancy outcome (91.57%) was significantly higher (p⩽0.05) in Group II compared to Group I (61.54%). Mean birthweight and mean APGAR score were found normal in both study groups. Only 2.75% of patients have warfarin embryopathy in Group I. Furthermore, comparison of SF-36 scores for HRQOL (Health-Related Quality of Life) before and after pregnancy were statistically insignificant among the study population.\n\n\n\nProper antenatal care and early risk stratification are the fundamental measures to improve the maternal and foetal outcomes in a patient with a prosthetic heart valve.", "affiliations": "Department of Cardiac Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.;Al Helal Specialized Hospital & Research Institute, Dhaka, Bangladesh.;Department of Cardiac Anesthesia, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.;Department of Community Medicine, Shaheed Suhrawardy Medical College, Dhaka, Bangladesh.;National Institute of Cardiovascular Diseases, Dhaka, Bangladesh.;Department of Cardiac Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.", "authors": "Ranjan|Redoy|R|0000-0003-1927-5023;Adhikary|Dipannita|D|;Saha|Sanjoy Kumar|SK|;Mandal|Sabita|S|;Hasan|Kamrul|K|;Adhikary|Asit Baran|AB|", "chemical_list": "D000925:Anticoagulants; D014859:Warfarin", "country": "England", "delete": false, "doi": "10.1177/0267659118817712", "fulltext": null, "fulltext_license": null, "issn_linking": "0267-6591", "issue": "34(6)", "journal": "Perfusion", "keywords": "pregnancy; prosthetic heart valve", "medline_ta": "Perfusion", "mesh_terms": "D000328:Adult; D000925:Anticoagulants; D001459:Bangladesh; D005260:Female; D005500:Follow-Up Studies; D006350:Heart Valve Prosthesis; D006470:Hemorrhage; D006801:Humans; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular; D011256:Pregnancy Outcome; D011788:Quality of Life; D012189:Retrospective Studies; D013923:Thromboembolism; D014859:Warfarin", "nlm_unique_id": "8700166", "other_id": null, "pages": "446-452", "pmc": null, "pmid": "30624139", "pubdate": "2019-09", "publication_types": "D016430:Clinical Trial; D016428:Journal Article; D016448:Multicenter Study", "references": null, "title": "Impact of prosthetic heart valves on pregnancy in Bangladeshi women.", "title_normalized": "impact of prosthetic heart valves on pregnancy in bangladeshi women" }

[ { "companynumb": "BD-FRESENIUS KABI-FK202008473", "fulfillexpeditecriteria": "1", "occurcountry": "BD", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "WARFARIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "WARFARIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "HEPARIN SODIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "017029", "drugbatchnumb": "UNKNOWN,UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HEPARIN (MANUFACTURER UNKNOWN)" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "HEPARIN SODIUM" }, "drugadditional": null, "drugadministrationroute": "058", "drugauthorizationnumb": "017029", "drugbatchnumb": "UNKNOWN,UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTICOAGULANT THERAPY", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "12", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5000", "drugstructuredosageunit": "025", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HEPARIN (MANUFACTURER UNKNOWN)" } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Exposure during pregnancy", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Postpartum haemorrhage", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Disseminated intravascular coagulation", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "RANJAN R, ADHIKARY D, SAHA S, MANDAL S, HASAN K, ADHIKARY A. IMPACT OF PROSTHETIC HEART VALVES ON PREGNANCY IN BANGLADESHI WOMEN. PERFUSION (LONDON). 2019 SEP?34 (6):446?452.", "literaturereference_normalized": "impact of prosthetic heart valves on pregnancy in bangladeshi women", "qualification": "3", "reportercountry": "BD" }, "primarysourcecountry": "BD", "receiptdate": "20200818", "receivedate": "20200818", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18168527, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" } ]

{ "abstract": "In the early 1990s, 20 haemophiliacs (HPs) were infected with a common source of HIV-1 viruses through the contaminated clotting factor IX. The aim of this study is to review 20 HPs infected with a common source of virus. The enrolled patients have been consecutively treated with Korean red ginseng (KRG), zidovudine (ZDV) or two-drug therapy and highly active antiretroviral therapy (HAART). We determined full-length pol gene over 20 years and human leukocyte antigen (HLA) class I with peripheral blood mononuclear cells and reviewed medical records. Eighteen HPs experienced various opportunistic infections or clinical manifestations. There were significant inverse correlations between the HLA prognostic score and the annual decrease in CD4+ T-cell counts prior to HAART (AD) (P < 0.05) and the amount of KRG and the AD (P < 0.01). From 1998, the HPs had been treated with HAART. Each of the two patients died without and with HAART regimen respectively. At present, 16 HPs have been alive with HAART. Among the 16 HPs, 12 and 4 are on HAART-plus-KRG and HAART only respectively. Eleven HPs including 2 HPs with G-to-A hypermutations had revealed resistance mutations. Ten and two HPs have shown poor adherence and incomplete viral suppres-sion on HAART respectively. Virological failure based on WHO guidelines was not observed on KRG-plus-HAART. Two HPs revealed additional resistance mutations against two classes on KRG-plus-HAART. As a nationwide study, we first report overall features on clinical course of Korean haemophiliacs. Further education on the importance of drug adherence is needed.", "affiliations": "Departments of Microbiology; and Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.", "authors": "Kim|B-R|BR|;Kim|J-E|JE|;Sung|H|H|;Cho|Y-K|YK|", "chemical_list": "D019380:Anti-HIV Agents; D054302:pol Gene Products, Human Immunodeficiency Virus", "country": "England", "delete": false, "doi": "10.1111/hae.12527", "fulltext": null, "fulltext_license": null, "issn_linking": "1351-8216", "issue": "21(1)", "journal": "Haemophilia : the official journal of the World Federation of Hemophilia", "keywords": "Korean red ginseng; a common source of HIV-1; adherence; contaminated clotting factor 9; haemophilia; resistance mutations", "medline_ta": "Haemophilia", "mesh_terms": "D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents; D015496:CD4-Positive T-Lymphocytes; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005500:Follow-Up Studies; D015658:HIV Infections; D015497:HIV-1; D006467:Hemophilia A; D006801:Humans; D055670:Medicine, Korean Traditional; D008969:Molecular Sequence Data; D009154:Mutation; D056910:Republic of Korea; D055815:Young Adult; D054302:pol Gene Products, Human Immunodeficiency Virus", "nlm_unique_id": "9442916", "other_id": null, "pages": "e1-11", "pmc": null, "pmid": "25545303", "pubdate": "2015-01", "publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't", "references": null, "title": "Long-term follow up of HIV-1-infected Korean haemophiliacs, after infection from a common source of virus.", "title_normalized": "long term follow up of hiv 1 infected korean haemophiliacs after infection from a common source of virus" }

[ { "companynumb": "KP-CIPLA LTD.-2015KP00461", "fulfillexpeditecriteria": "1", "occurcountry": "KP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LOPINAVIR\\RITONAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200211", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOPINAVIR/RITONAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ATAZANAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200805", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATAZANAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "ORAL SOLUTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "199411", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INDINAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "199812", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INDINAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RITONAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200805", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITONAVIR." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haemorrhage", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Haematoma", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Gastric ulcer haemorrhage", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Anaemia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Herpes zoster", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 199407" } }, "primarysource": { "literaturereference": "CHO.Y.-K., KIM.B.-R.,KIM.J.-E, KIM.H. LONG-TERM FOLLOW UP OF HIV-1-INFECTED KOREAN HAEMOPHILIACS, AFTER INFECTION FROM A COMMON SOURCE OF VIRUS. HAEMOPHILIA. 2015;21:E1-E11", "literaturereference_normalized": "long term follow up of hiv 1 infected korean haemophiliacs after infection from a common source of virus", "qualification": "3", "reportercountry": "KP" }, "primarysourcecountry": "KP", "receiptdate": "20150123", "receivedate": "20150123", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10732908, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "KP-CIPLA LTD.-2015SA00513", "fulfillexpeditecriteria": "1", "occurcountry": "KP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "RITONAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201301", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITONAVIR." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ATAZANAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200501", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATAZANAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RITONAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200808", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITONAVIR." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200501", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "STAVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "078030", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "DRY SYRUP", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200501", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "STAVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ABACAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201306", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ABACAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ATAZANAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200808", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATAZANAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "UNSPECIFIED INGREDIENT" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HIGHLY ACTIVE ANTIRETROVIRAL THERAPY" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "STAVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "078030", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "DRY SYRUP", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200808", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "STAVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200808", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ATAZANAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201306", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATAZANAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIETARY SUPPLEMENT" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "KOREAN RED GINSENG" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pyelonephritis", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Oesophageal ulcer", "reactionmeddraversionpt": "18.0", "reactionoutcome": null }, { "reactionmeddrapt": "Herpes zoster", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug resistance", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cytomegalovirus infection", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 200501" } }, "primarysource": { "literaturereference": "B R KIM, J E KIM, H SUNG, Y K.CHO. LONG-TERM FOLLOW UP OF HIV-1-INFECTED KOREAN HAEMOPHILIACS, AFTER INFECTION FROM A COMMON SOURCE OF VIRUS. HAEMOPHILIA. 2015;21:1-11", "literaturereference_normalized": "long term follow up of hiv 1 infected korean haemophiliacs after infection from a common source of virus", "qualification": "3", "reportercountry": "KP" }, "primarysourcecountry": "KP", "receiptdate": "20150123", "receivedate": "20150123", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10733216, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "KP-CIPLA LTD.-2015KP00459", "fulfillexpeditecriteria": "1", "occurcountry": "KP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "ORAL SOLUTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "199305", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIDANOSINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "199707", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIDANOSINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "199712", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ABACAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION (EXCEPT SYRUP)", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200807", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ABACAVIR" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Multi-organ failure", "reactionmeddraversionpt": "18.0", "reactionoutcome": "5" }, { "reactionmeddrapt": "Femoral neck fracture", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Oral candidiasis", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Osteoarthritis", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Amputation", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Haematuria", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Weight decreased", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 199106" } }, "primarysource": { "literaturereference": "CHO.Y.-K., KIM.B.-R.,KIM.J.-E, KIM.H. LONG-TERM FOLLOW UP OF HIV-1-INFECTED KOREAN HAEMOPHILIACS, AFTER INFECTION FROM A COMMON SOURCE OF VIRUS. HAEMOPHILIA. 2015;21:E1?E11", "literaturereference_normalized": "long term follow up of hiv 1 infected korean haemophiliacs after infection from a common source of virus", "qualification": "3", "reportercountry": "KP" }, "primarysourcecountry": "KP", "receiptdate": "20150123", "receivedate": "20150123", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10732749, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "KP-CIPLA LTD.-2015KP00511", "fulfillexpeditecriteria": "1", "occurcountry": "KP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LOPINAVIR\\RITONAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201101", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOPINAVIR/RITONAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "077980", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201101", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "077980", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200706", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIETARY SUPPLEMENT" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "199305", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "KOREAN RED GINSENG" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "UNSPECIFIED INGREDIENT" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HIGHLY ACTIVE ANTIRETROVIRAL THERAPY" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200706", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201101", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cerebral infarction", "reactionmeddraversionpt": "18.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "B R KIM, J E KIM, H SUNG, Y K.CHO. LONG-TERM FOLLOW UP OF HIV-1-INFECTED KOREAN HAEMOPHILIACS, AFTER INFECTION FROM A COMMON SOURCE OF VIRUS. HAEMOPHILIA. 2015;21:1-11", "literaturereference_normalized": "long term follow up of hiv 1 infected korean haemophiliacs after infection from a common source of virus", "qualification": "3", "reportercountry": "KP" }, "primarysourcecountry": "KP", "receiptdate": "20150123", "receivedate": "20150123", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10732940, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150721" }, { "companynumb": "KP-CIPLA LTD.-2015KP00327", "fulfillexpeditecriteria": "1", "occurcountry": "KP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "090561", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIETARY SUPPLEMENT" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "KOREAN RED GINSENG" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Death", "reactionmeddraversionpt": "18.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "KIM B, KIM J, SUNG H, CHO Y. LONG-TERM FOLLOW UP OF HIV-1-INFECTED KOREAN HAEMOPHILIACS, AFTER INFECTION FROM A COMMON SOURCE OF VIRUS. HAEMOPHILIA. 2015;21(1):1-11", "literaturereference_normalized": "long term follow up of hiv 1 infected korean haemophiliacs after infection from a common source of virus", "qualification": "3", "reportercountry": "KP" }, "primarysourcecountry": "KP", "receiptdate": "20150119", "receivedate": "20150119", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10718425, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150721" }, { "companynumb": "KP-CIPLA LTD.-2015KP00514", "fulfillexpeditecriteria": "1", "occurcountry": "KP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "NELFINAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200311", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NELFINAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "077980", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201211", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200508", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIETARY SUPPLEMENT" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200305", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "KOREAN RED GINSENG" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ATAZANAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200508", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATAZANAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "UNSPECIFIED INGREDIENT" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200311", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HIGHLY ACTIVE ANTIRETROVIRAL THERAPY" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "077980", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200508", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200311", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201211", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "077980", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200311", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Oral candidiasis", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Splenomegaly", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Lymph node tuberculosis", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 200311" } }, "primarysource": { "literaturereference": "B R KIM, J E KIM, H SUNG, Y K.CHO. LONG-TERM FOLLOW UP OF HIV-1-INFECTED KOREAN HAEMOPHILIACS, AFTER INFECTION FROM A COMMON SOURCE OF VIRUS. HAEMOPHILIA. 2015;21:1-11", "literaturereference_normalized": "long term follow up of hiv 1 infected korean haemophiliacs after infection from a common source of virus", "qualification": "3", "reportercountry": "KP" }, "primarysourcecountry": "KP", "receiptdate": "20150123", "receivedate": "20150123", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10732973, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "KP-CIPLA LTD.-2015KP00460", "fulfillexpeditecriteria": "1", "occurcountry": "KP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "ORAL SOLUTION", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "1999", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "STAVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200105", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "STAVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIETARY SUPPLEMENT" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "640 DAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "KOREAN RED GINSENG" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LOPINAVIR\\RITONAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201006", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOPINAVIR/RITONAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200105", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIDANOSINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "1999", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIDANOSINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ATAZANAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200610", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATAZANAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INDINAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200105", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INDINAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "NELFINAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200204", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NELFINAVIR" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cataract", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cytomegalovirus chorioretinitis", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Herpes zoster", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Weight decreased", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Blindness", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 1998" } }, "primarysource": { "literaturereference": "CHO.Y.-K., KIM.B.-R.,KIM.J.-E, KIM.H. LONG-TERM FOLLOW UP OF HIV-1-INFECTED KOREAN HAEMOPHILIACS, AFTER INFECTION FROM A COMMON SOURCE OF VIRUS. HAEMOPHILIA. 2015;21:E1-E11", "literaturereference_normalized": "long term follow up of hiv 1 infected korean haemophiliacs after infection from a common source of virus", "qualification": "3", "reportercountry": "KP" }, "primarysourcecountry": "KP", "receiptdate": "20150123", "receivedate": "20150123", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10732893, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" } ]

{ "abstract": "BACKGROUND\nData are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma.\n\n\nMETHODS\nBetween April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15).\n\n\nRESULTS\nThe study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide. At a median follow-up of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229 patients who received placebo (58%) had disease progression or had died. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P=0.03). More grade 3 or 4 hematologic adverse events and grade 3 nonhematologic adverse events occurred in patients who received lenalidomide (P<0.001 for both comparisons). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%).\n\n\nCONCLUSIONS\nLenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.).", "affiliations": "Blood and Marrow Transplant Program, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. philip.mccarthy@roswellpark.org", "authors": "McCarthy|Philip L|PL|;Owzar|Kouros|K|;Hofmeister|Craig C|CC|;Hurd|David D|DD|;Hassoun|Hani|H|;Richardson|Paul G|PG|;Giralt|Sergio|S|;Stadtmauer|Edward A|EA|;Weisdorf|Daniel J|DJ|;Vij|Ravi|R|;Moreb|Jan S|JS|;Callander|Natalie Scott|NS|;Van Besien|Koen|K|;Gentile|Teresa|T|;Isola|Luis|L|;Maziarz|Richard T|RT|;Gabriel|Don A|DA|;Bashey|Asad|A|;Landau|Heather|H|;Martin|Thomas|T|;Qazilbash|Muzaffar H|MH|;Levitan|Denise|D|;McClune|Brian|B|;Schlossman|Robert|R|;Hars|Vera|V|;Postiglione|John|J|;Jiang|Chen|C|;Bennett|Elizabeth|E|;Barry|Susan|S|;Bressler|Linda|L|;Kelly|Michael|M|;Seiler|Michele|M|;Rosenbaum|Cara|C|;Hari|Parameswaran|P|;Pasquini|Marcelo C|MC|;Horowitz|Mary M|MM|;Shea|Thomas C|TC|;Devine|Steven M|SM|;Anderson|Kenneth C|KC|;Linker|Charles|C|", "chemical_list": "D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide", "country": "United States", "delete": false, "doi": "10.1056/NEJMoa1114083", "fulltext": null, "fulltext_license": null, "issn_linking": "0028-4793", "issue": "366(19)", "journal": "The New England journal of medicine", "keywords": null, "medline_ta": "N Engl J Med", "mesh_terms": "D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma; D016609:Neoplasms, Second Primary; D033581:Stem Cell Transplantation; D013792:Thalidomide", "nlm_unique_id": "0255562", "other_id": null, "pages": "1770-81", "pmc": null, "pmid": "22571201", "pubdate": "2012-05-10", "publication_types": "D017428:Clinical Trial, Phase III; D016428:Journal Article; D016448:Multicenter Study; D016449:Randomized Controlled Trial; D052061:Research Support, N.I.H., Extramural", "references": "1111463;17646864;17209057;3279997;18669875;5273282;12384400;5270658;22571200;20085933;21962393;21410373;21482708;9753033;7165009;17975015;22571202;22160383;21146205;22021371;11964279;19273705;21795746;21054148;19880501;19826130;18492953;16873668;20308672;11142483;16855634;19861683;20048187", "title": "Lenalidomide after stem-cell transplantation for multiple myeloma.", "title_normalized": "lenalidomide after stem cell transplantation for multiple myeloma" }

[ { "companynumb": "US-CELGENEUS-USA-20191201392", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LENALIDOMIDE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "021880", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULES", "drugdosagetext": null, "drugenddate": "2006", "drugenddateformat": "602", "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "REVLIMID" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "THALIDOMIDE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "020785", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULES", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THALOMID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOXORUBICIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXORUBICIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MELPHALAN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MELPHALAN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "VINCRISTINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VINCRISTINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LENALIDOMIDE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "021880", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CAPSULES", "drugdosagetext": "10 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "PLASMA CELL MYELOMA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "REVLIMID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "GRANULOCYTE COLONY-STIMULATING FACTOR NOS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GRANULOCYTE COLONY STIMULATING FACTOR" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." } ], "patientagegroup": null, "patientonsetage": "67", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "B-cell type acute leukaemia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Basal cell carcinoma", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Malignant melanoma", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Squamous cell carcinoma of skin", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Neuropathy peripheral", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MCCARTHY P. LENALIDOMIDE AFTER STEM?CELL TRANSPLANTATION FOR MULTIPLE MYELOMA. N ENGL J MED. AUTHOR MANUSCRIPT. 2012 MAY 10?366(19):1770?1781.", "literaturereference_normalized": "lenalidomide after stem cell transplantation for multiple myeloma", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200721", "receivedate": "20191209", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17131397, "safetyreportversion": 6, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201102" } ]

{ "abstract": "Stevens-Johnson syndrome (SJS) is an uncommon life-threatening skin disease, generally induced by drugs. Extracutaneous manifestations of the syndrome can occur, and may involve the conjunctiva, buccal mucosa, gastrointestinal and genitourinary tracts. Cholestatic hepatitis has been rarely described in SJS. A 29-year-old woman was admitted with generalized cutaneous eruption. A self-medication with paracetamol had been started three days earlier. Clinical signs and skin biopsy were consistent with SJS. Five days later, the patient developed jaundice. Serial liver function tests showed rising transaminases, bilirubin, alkaline phosphatase and γ-glutamyl transferase. Liver biopsy was performed and was consistent with the diagnosis of drug-induced cholestatic hepatitis. Adequate supportive care was provided to the patient. Skin lesions disappeared within two weeks. Jaundice disappeared progressively, and liver tests returned to normal. Herein, we report the first case of SJS associated with cholestatic hepatitis after ingestion of therapeutic doses of paracetamol.", "affiliations": "Departement de Pharmacologie Clinique, Faculte de Medecine de Sousse, Avenue Mohamed Karoui, 4002 Sousse, B.P.: 126, Tunisia. raoudha_slim3@yahoo.fr.", "authors": "Slim|Raoudha|R|;Fathallah|Neila|N|;Aounallah|Amina|A|;Ksiaa|Mehdi|M|;Sriha|Badreddine|B|;Nouira|Rafiaa|R|;Ben Salem|Chaker|C|", "chemical_list": "D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen", "country": "United Arab Emirates", "delete": false, "doi": "10.2174/1574886309666140827122735", "fulltext": null, "fulltext_license": null, "issn_linking": "1574-8863", "issue": "10(2)", "journal": "Current drug safety", "keywords": null, "medline_ta": "Curr Drug Saf", "mesh_terms": "D000082:Acetaminophen; D000328:Adult; D018712:Analgesics, Non-Narcotic; D056486:Chemical and Drug Induced Liver Injury; D003875:Drug Eruptions; D005260:Female; D006261:Headache; D006801:Humans; D041781:Jaundice, Obstructive; D008111:Liver Function Tests; D012867:Skin; D013262:Stevens-Johnson Syndrome", "nlm_unique_id": "101270895", "other_id": null, "pages": "187-9", "pmc": null, "pmid": "25158788", "pubdate": "2015", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Paracetamol-induced Stevens Johnson syndrome and cholestatic hepatitis.", "title_normalized": "paracetamol induced stevens johnson syndrome and cholestatic hepatitis" }

[ { "companynumb": "TN-SUN PHARMACEUTICAL INDUSTRIES LTD-2015RR-099864", "fulfillexpeditecriteria": "1", "occurcountry": "TN", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "ACETAMINOPHEN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "76200", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEADACHE", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "12", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PARACETAMOL" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Self-medication", "reactionmeddraversionpt": "18.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Stevens-Johnson syndrome", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hepatitis cholestatic", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "SLIM R, FATHALLAH N, AOUNALLAH A, KSIAA M, SRIHA B, NOUIRA R, ET AL. PARACETAMOL-INDUCED STEVENS JOHNSON SYNDROME AND CHOLESTATIC HEPATITIS. CURR-DRUG-SAF. 2015;10 (2):187-189", "literaturereference_normalized": "paracetamol induced stevens johnson syndrome and cholestatic hepatitis", "qualification": "3", "reportercountry": "TN" }, "primarysourcecountry": "TN", "receiptdate": "20150820", "receivedate": "20150707", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11242898, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": null, "transmissiondate": "20151125" } ]

{ "abstract": "Sorafenib and dacarbazine have low single-agent response rates in metastatic sarcomas. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of sorafenib and dacarbazine in select sarcoma subtypes.\n\n\n\nPatients with leiomyosarcoma (LMS), synovial sarcoma (SS), or malignant peripheral nerve sheath tumors (MPNST) with up to two previous lines of therapy and adequate hepatic, renal, and marrow function received 3-week cycles of sorafenib at 400 mg oral twice daily and dacarbazine 1,000 mg/m2 intravenously (later reduced to 850 mg/m2). Patients were evaluated for response every 6 weeks. The primary objective was to determine the disease control rate (DCR) of sorafenib plus dacarbazine in the selected sarcoma subtypes.\n\n\n\nThe study included 37 patients (19 female); median age was 55 years (range 26-87); and histologies included LMS (22), SS (11), and MPNST (4). The DCR was 46% (17/37). Median progression-free survival was 13.4 weeks. The RECIST response rate was 14% (5/37). The Choi response rate was 51% (19/37). Median overall survival was 13.2 months. Of the first 25 patients, 15 (60%) required dacarbazine dose reductions for hematologic toxicity, with one episode of grade 5 neutropenic fever. After reducing the starting dose of dacarbazine to 850 mg/m2, only 3 of the final 12 (25%) patients required dose reduction.\n\n\n\nThis phase II study met its primary endpoint with an 18-week DCR of 46%. The clinical activity of dacarbazine plus sorafenib in patients with these diagnoses is modest.\n\n\n\nMetastatic soft tissue sarcomas are a heterogeneous group of relatively rare malignancies. Most patients are treated with cytotoxic chemotherapy or targeted therapy in the form of tyrosine kinase inhibitors. Response rates are relatively low, and there is a need for better therapies. This clinical trial demonstrates that combining a cytotoxic therapy (dacarbazine) with an antiangiogenic small molecule (sorafenib) is feasible and associated with favorable disease-control rates; however, it also increases the potential for significant toxicity.", "affiliations": "Eisai, Inc., Woodcliff Lake, New Jersey, USA.;Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA dicksonm@mskcc.org.;Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.;Department of Medicine, Columbia University, New York, New York, USA.;Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.;Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.;Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.;Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.;Department of Biostatistics, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.;Department of Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.;Department of Radiology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.;Monter Cancer Center, Lake Success, New York, USA.;Department of Medicine, Columbia University, New York, New York, USA.;Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.", "authors": "D'Adamo|David R|DR|;Dickson|Mark A|MA|;Keohan|Mary L|ML|;Carvajal|Richard D|RD|;Hensley|Martee L|ML|;Hirst|Catherine M|CM|;Ezeoke|Marietta O|MO|;Ahn|Linda|L|;Qin|Li-Xuan|LX|;Antonescu|Cristina R|CR|;Lefkowitz|Robert A|RA|;Maki|Robert G|RG|;Schwartz|Gary K|GK|;Tap|William D|WD|", "chemical_list": "D003606:Dacarbazine; D000077157:Sorafenib", "country": "United States", "delete": false, "doi": "10.1634/theoncologist.2018-0160", "fulltext": null, "fulltext_license": null, "issn_linking": "1083-7159", "issue": "24(6)", "journal": "The oncologist", "keywords": "Angiogenesis; Chemotherapy; Phase II clinical trials; Soft tissue sarcoma", "medline_ta": "Oncologist", "mesh_terms": "D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D003606:Dacarbazine; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D064147:Febrile Neutropenia; D005260:Female; D006801:Humans; D007890:Leiomyosarcoma; D008297:Male; D008875:Middle Aged; D018319:Neurofibrosarcoma; D000077982:Progression-Free Survival; D066066:Response Evaluation Criteria in Solid Tumors; D013584:Sarcoma, Synovial; D012720:Severity of Illness Index; D000077157:Sorafenib", "nlm_unique_id": "9607837", "other_id": null, "pages": "857-863", "pmc": null, "pmid": "30126857", "pubdate": "2019-06", "publication_types": "D017427:Clinical Trial, Phase II; D016428:Journal Article; D052061:Research Support, N.I.H., Extramural; D013485:Research Support, Non-U.S. Gov't", "references": "18445842;10912948;17470866;11905672;20212250;22595799;27291997;4938153;16636341;15870716;17215530;28055103;17634494;8315424;18650514;17167137;15175435;11313175;17442997;15946591;3479329;16496406;18534250;8315425;20821331;19451436;1868027;17470865;10811673;19349552;11872347;17976362;20016927;16192597;26371143;12065559;25713428;18394689;15466206;3585441;12503822", "title": "A Phase II Trial of Sorafenib and Dacarbazine for Leiomyosarcoma, Synovial Sarcoma, and Malignant Peripheral Nerve Sheath Tumors.", "title_normalized": "a phase ii trial of sorafenib and dacarbazine for leiomyosarcoma synovial sarcoma and malignant peripheral nerve sheath tumors" }

[ { "companynumb": "US-PFIZER INC-2017010248", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "SORAFENIB" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG, 2X/DAY (3-WEEK CYCLE)", "drugenddate": null, "drugenddateformat": null, "drugindication": "SYNOVIAL SARCOMA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SORAFENIB" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DACARBAZINE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "075940", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "POWDER FOR INJECTION", "drugdosagetext": "1000 MG/M2, EVERY 3 WEEKS (1-HOUR INTRAVENOUS INFUSION)", "drugenddate": null, "drugenddateformat": null, "drugindication": "SYNOVIAL SARCOMA", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DACARBAZINE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Febrile neutropenia", "reactionmeddraversionpt": "22.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "D^ADAMO, D.. A PHASE II TRIAL OF SORAFENIB AND DACARBAZINE FOR LEIOMYOSARCOMA, SYNOVIAL SARCOMA, AND MALIGNANT PERIPHERAL NERVE SHEATH TUMORS. THE ONCOLOGIST. 2019?24 (6):857-863", "literaturereference_normalized": "a phase ii trial of sorafenib and dacarbazine for leiomyosarcoma synovial sarcoma and malignant peripheral nerve sheath tumors", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20191125", "receivedate": "20170112", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 13111041, "safetyreportversion": 4, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200122" } ]

{ "abstract": "Although imatinib is not considered a predisposing factor for tuberculosis (TB), the present case report describes three patients in whom imatinib treatment for chronic myeloid leukaemia was complicated by TB. This raises the question of whether imatinib increases susceptibility to TB. There are several reports suggesting that imatinib might impair the immune system, leading to a variety of infections, including varicella zoster and hepatitis B. Control of TB in healthy individuals is achieved through acquired immunity, in which antigen-specific T-cells and macrophages arrest growth of Mycobacterium tuberculosis bacilli and maintain control over persistent bacilli. In the chronic stage of the infection, CD8+ T-cells assist macrophages in controlling intracellular mycobacteria. The T-cell receptor orchestrates this process. The fact that tyrosine kinases play an important role in T-cell receptor signal transduction and that imatinib has been shown to affect T-cell receptor signal transduction, presents a mechanism by which imatinib might impair control of Mycobacterium tuberculosis; thereby leaving the host susceptible to reactivation of tuberculosis.", "affiliations": "Department of Pulmonary Diseases, VU University Medical Centre, Amsterdam, The Netherlands. j.m.a.daniels@mca.nl", "authors": "Daniels|J M A|JM|;Vonk-Noordegraaf|A|A|;Janssen|J J W M|JJ|;Postmus|P E|PE|;van Altena|R|R|", "chemical_list": "D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate", "country": "England", "delete": false, "doi": "10.1183/09031936.00025408", "fulltext": null, "fulltext_license": null, "issn_linking": "0903-1936", "issue": "33(3)", "journal": "The European respiratory journal", "keywords": null, "medline_ta": "Eur Respir J", "mesh_terms": "D000328:Adult; D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D001549:Benzamides; D018414:CD8-Positive T-Lymphocytes; D006801:Humans; D000068877:Imatinib Mesylate; D007107:Immune System; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008297:Male; D009169:Mycobacterium tuberculosis; D010879:Piperazines; D011743:Pyrimidines; D015398:Signal Transduction; D016896:Treatment Outcome; D014376:Tuberculosis", "nlm_unique_id": "8803460", "other_id": null, "pages": "670-2", "pmc": null, "pmid": "19251803", "pubdate": "2009-03", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia.", "title_normalized": "tuberculosis complicating imatinib treatment for chronic myeloid leukaemia" }

[ { "companynumb": "NL-MYLANLABS-2020M1027075", "fulfillexpeditecriteria": "1", "occurcountry": "NL", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "204644", "drugbatchnumb": "UNK", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC MYELOID LEUKAEMIA", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMATINIB." } ], "patientagegroup": null, "patientonsetage": "19", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Weight decreased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Tuberculosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pulmonary cavitation", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cough", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "DANIELS JMA, VONK-NOORDEGRAAF A, JANSSEN JJWM, POSTMUS PE AND ALTENA RV.. TUBERCULOSIS COMPLICATING IMATINIB TREATMENT FOR CHRONIC MYELOID LEUKAEMIA.. EUROPEAN RESPIRATORY JOURNAL. 2009?33(3):670-672", "literaturereference_normalized": "tuberculosis complicating imatinib treatment for chronic myeloid leukaemia", "qualification": "3", "reportercountry": "NL" }, "primarysourcecountry": "NL", "receiptdate": "20200317", "receivedate": "20200317", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17550277, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200409" }, { "companynumb": "NL-MYLANLABS-2020M1026477", "fulfillexpeditecriteria": "1", "occurcountry": "NL", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "204644", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC MYELOID LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMATINIB." } ], "patientagegroup": null, "patientonsetage": "26", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tuberculosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Aspartate aminotransferase increased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bone tuberculosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Back pain", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Alanine aminotransferase increased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Red blood cell sedimentation rate increased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "White blood cell count increased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "DANIELS JMA, VONK-NOORDEGRAAF A, JANSSEN JJWM, POSTMUS PE AND ALTENA RV.. TUBERCULOSIS COMPLICATING IMATINIB TREATMENT FOR CHRONIC MYELOID LEUKAEMIA.. EUROPEAN RESPIRATORY JOURNAL. 2009?33(3):670-672", "literaturereference_normalized": "tuberculosis complicating imatinib treatment for chronic myeloid leukaemia", "qualification": "3", "reportercountry": "NL" }, "primarysourcecountry": "NL", "receiptdate": "20200316", "receivedate": "20200316", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17545586, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200409" }, { "companynumb": "PHHY2009NL12125", "fulfillexpeditecriteria": "1", "occurcountry": "NL", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "021588", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC MYELOID LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMATINIB." } ], "patientagegroup": null, "patientonsetage": "26", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tuberculosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "White blood cell count increased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bone tuberculosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Alanine aminotransferase increased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Back pain", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Aspartate aminotransferase increased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Red blood cell sedimentation rate increased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "DANIELS JMA, VONK-NOORDEGRAAF A, JANSSEN JJWM, POSTMUS PE AND ALTENA RV. TUBERCULOSIS COMPLICATING IMATINIB TREATMENT FOR CHRONIC MYELOID LEUKAEMIA. EUROPEAN RESPIRATORY JOURNAL. 2009?33(3):670-672", "literaturereference_normalized": "tuberculosis complicating imatinib treatment for chronic myeloid leukaemia", "qualification": "3", "reportercountry": "NL" }, "primarysourcecountry": "NL", "receiptdate": "20200212", "receivedate": "20090408", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 6963199, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200409" }, { "companynumb": "PHHY2009NL12126", "fulfillexpeditecriteria": "1", "occurcountry": "NL", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "021588", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC MYELOID LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMATINIB." } ], "patientagegroup": null, "patientonsetage": "19", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tuberculosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Haemoglobin decreased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pulmonary cavitation", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cough", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Weight decreased", "reactionmeddraversionpt": "22.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "DANIELS JMA, VONK-NOORDEGRAAF A, JANSSEN JJWM, POSTMUS PE AND ALTENA RV. TUBERCULOSIS COMPLICATING IMATINIB TREATMENT FOR CHRONIC MYELOID LEUKAEMIA. EUROPEAN RESPIRATORY JOURNAL. 2009?33(3):670-672", "literaturereference_normalized": "tuberculosis complicating imatinib treatment for chronic myeloid leukaemia", "qualification": "3", "reportercountry": "NL" }, "primarysourcecountry": "NL", "receiptdate": "20200214", "receivedate": "20090408", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 6963590, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200409" }, { "companynumb": "PHHY2009NL12115", "fulfillexpeditecriteria": "1", "occurcountry": "NL", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYTARABINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC MYELOID LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYTARABINE." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "021588", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC MYELOID LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMATINIB." } ], "patientagegroup": null, "patientonsetage": "38", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fatigue", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Productive cough", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Night sweats", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tuberculosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pulmonary cavitation", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "DANIELS JMA, VONK-NOORDEGRAAF A, JANSSEN JJWM, POSTMUS PE AND VAN ALTENA R. TUBERCULOSIS COMPLICATING IMATINIB TREATMENT FOR CHRONIC MYELOID LEUKAEMIA. EUROPEAN RESPIRATORY JOURNAL. 2009?33(3):670-672", "literaturereference_normalized": "tuberculosis complicating imatinib treatment for chronic myeloid leukaemia", "qualification": "3", "reportercountry": "NL" }, "primarysourcecountry": "NL", "receiptdate": "20200211", "receivedate": "20090409", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 6964750, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200409" }, { "companynumb": "NL-MYLANLABS-2020M1026476", "fulfillexpeditecriteria": "1", "occurcountry": "NL", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYTARABINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK MG/M2", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC MYELOID LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYTARABINE." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "204644", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC MYELOID LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMATINIB." } ], "patientagegroup": null, "patientonsetage": "38", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Productive cough", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Fatigue", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tuberculosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pulmonary cavitation", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Night sweats", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "DANIELS JMA, VONK-NOORDEGRAAF A, JANSSEN JJWM, POSTMUS PE AND VAN ALTENA R. TUBERCULOSIS COMPLICATING IMATINIB TREATMENT FOR CHRONIC MYELOID LEUKAEMIA.. EUROPEAN RESPIRATORY JOURNAL. 2009?33(3):670-672", "literaturereference_normalized": "tuberculosis complicating imatinib treatment for chronic myeloid leukaemia", "qualification": "3", "reportercountry": "NL" }, "primarysourcecountry": "NL", "receiptdate": "20200316", "receivedate": "20200316", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17545585, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200409" }, { "companynumb": "NL-PFIZER INC-2020081780", "fulfillexpeditecriteria": "1", "occurcountry": "NL", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYTARABINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "071868", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200 MG/M2, CYCLIC", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC MYELOID LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYTARABINE." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "IMATINIB MESYLATE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "800 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC MYELOID LEUKAEMIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "800", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMATINIB." } ], "patientagegroup": null, "patientonsetage": "38", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tuberculosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pulmonary cavitation", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "DANIELS, J.. TUBERCULOSIS COMPLICATING IMATINIB TREATMENT FOR CHRONIC MYELOID LEUKAEMIA.. EUROPEAN RESPIRATORY JOURNAL. 2009?33:DOI:10.1183/09031936.00025408", "literaturereference_normalized": "tuberculosis complicating imatinib treatment for chronic myeloid leukaemia", "qualification": "3", "reportercountry": "NL" }, "primarysourcecountry": "NL", "receiptdate": "20200303", "receivedate": "20200227", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17469831, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200409" } ]

{ "abstract": "Management of inflammation after surgery for recalcitrant anterior uveitis is challenging. Herein, we report successful treatment using intracameral injection of recombinant tissue plasminogen activator (rtPA) in two patients with recalcitrant anterior uveitis, due to infective uveitis and Vogt-Koyanagi-Harada disease, respectively. A 40-year-old woman presented with bilateral redness and vision reduction that had persisted 2 weeks. She also had bilateral anterior uveitis, vasculitis, retinitis, and optic disc swelling. Serology was positive for Bartonella henselae and Toxoplasma gondii. She was treated using long-term systemic corticosteroids and appropriate antibiotics. Our second case; a healthy 30-year-old man with bilateral eye redness and reduced vision without pain, and associated with headache and tinnitus for 1 weeks. He showed bilateral granulomatous inflammation with vitritis, choroiditis, retinitis, and hyperemic optic disc. The patient was diagnosed with Vogt-Koyanagi-Harada disease and treated with systemic corticosteroids. Both patients developed secondary cataracts and glaucoma that necessitated surgical intervention. Persistent chronic inflammation led to the formation of a thick fibrin membrane anterior to the intraocular lens (IOL) after phacoemulsification surgery with IOL implantation. This membrane was removed surgically, and intracameral injection of rtPA (25 μg) was carried out. The persistent inflammation had resolved and visual acuity had significantly improved within 1 week of intracameral rtPA injection. There were no reported ocular or systemic side effects. Intracameral rtPA is beneficial in patients with recalcitrant anterior uveitis who have undergone intraocular surgery. In most cases, surgical intervention improves the patients' vision. Intracameral rtPA should be considered in cases of persistent inflammation of varying etiology.", "affiliations": "Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kota Bharu, Malaysia.;Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kota Bharu, Malaysia.;Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kota Bharu, Malaysia.;Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kota Bharu, Malaysia.;Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kota Bharu, Malaysia.;Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kota Bharu, Malaysia.", "authors": "Patrick|Sylves|S|;Hui-Tze|Chan|C|;Wan-Hazabbah|Wan Hitam|WH|;Zunaina|Embong|E|;Azhany|Yaakub|Y|;Liza-Sharmini|Ahmad Tajudin|AT|", "chemical_list": null, "country": "Saudi Arabia", "delete": false, "doi": "10.1016/j.jtumed.2018.03.005", "fulltext": "\n==== Front\nJ Taibah Univ Med SciJ Taibah Univ Med SciJournal of Taibah University Medical Sciences1658-3612Taibah University S1658-3612(18)30030-110.1016/j.jtumed.2018.03.005Case ReportUse of recombinant tissue plasminogen activator for treatment of recalcitrant anterior uveitis: A case series Patrick Sylves MDHui-Tze Chan MBBSWan-Hazabbah Wan Hitam MSurgZunaina Embong MMedAzhany Yaakub MMedLiza-Sharmini Ahmad Tajudin MMedliza@usm.my∗Department of Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kota Bharu, Malaysia∗ Corresponding address: Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kota Bharu, Kelantan, Malaysia. liza@usm.my06 4 2018 10 2018 06 4 2018 13 5 483 487 27 1 2018 6 3 2018 14 3 2018 © 2018 The Authors2018This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Management of inflammation after surgery for recalcitrant anterior uveitis is challenging. Herein, we report successful treatment using intracameral injection of recombinant tissue plasminogen activator (rtPA) in two patients with recalcitrant anterior uveitis, due to infective uveitis and Vogt–Koyanagi–Harada disease, respectively. A 40-year-old woman presented with bilateral redness and vision reduction that had persisted 2 weeks. She also had bilateral anterior uveitis, vasculitis, retinitis, and optic disc swelling. Serology was positive for Bartonella henselae and Toxoplasma gondii. She was treated using long-term systemic corticosteroids and appropriate antibiotics. Our second case; a healthy 30-year-old man with bilateral eye redness and reduced vision without pain, and associated with headache and tinnitus for 1 weeks. He showed bilateral granulomatous inflammation with vitritis, choroiditis, retinitis, and hyperemic optic disc. The patient was diagnosed with Vogt-Koyanagi-Harada disease and treated with systemic corticosteroids. Both patients developed secondary cataracts and glaucoma that necessitated surgical intervention. Persistent chronic inflammation led to the formation of a thick fibrin membrane anterior to the intraocular lens (IOL) after phacoemulsification surgery with IOL implantation. This membrane was removed surgically, and intracameral injection of rtPA (25 μg) was carried out. The persistent inflammation had resolved and visual acuity had significantly improved within 1 week of intracameral rtPA injection. There were no reported ocular or systemic side effects. Intracameral rtPA is beneficial in patients with recalcitrant anterior uveitis who have undergone intraocular surgery. In most cases, surgical intervention improves the patients' vision. Intracameral rtPA should be considered in cases of persistent inflammation of varying etiology.\n\nالملخص\nعلاج التهاب القزحية الأمامية المتكرر بعد العملية الجراحية أمر صعب. نقدم هنا تقريرا عن معالجة ناجحة لحالتين بالحقن التجويفي لمنشط البلازمينوجين النسيجي المركب في حالتين من حالات التهاب القزحية الأمامية المتكرر؛ حالة التهاب القزحية الأمامية المعدي وحالة \" فوت-كويناقي-هرادا\". أُصيبت سيدة في الأربعين من العمر باحمرار في العينين وضعف الرؤية لمدة أسبوعين. كان لديها التهاب القزحية الأمامية، والتهاب الأوعية الدموية، والتهاب الشبكية، وتورم القرص البصري. وكانت اختبارات الأمصال لبكتريا بارتونيلا هنسيلي وتوكسوبلازما جوندياي موجبة. تم علاجها بالكورتيكوستيرويدات العامة على المدى الطويل والمضادات الحيوية المناسبة. كانت حالتنا الثانية رجلا سليما يبلغ من العمر ٣٠ عاما ظهر لديه احمرار غير مؤلم في العينين مع ضعف في الرؤية وصداع وطنين لمدة أسبوعين. كان هناك التهاب حبيبي في العينين مع التهاب السائل الثقيل والكورويد والشبكية مع احمرار القرص البصري. وتم تشخيصه على أنه حالة \" فوت-كويناقي-هرادا\" وتم علاجه بالكورتيكوستيرويدات العامة. نتج لدى الحالتين إعتام ثانوي في عدسة العين والماء الأزرق الذي استدعي التدخل الجراحي. أدى الالتهاب المزمن المستمر إلى تكوين غشاء ليفي سميك أمام العدسة بعد جراحة استحلاب العدسة مع زراعة عدسة جديدة. بعد ذلك أُزيل الغشاء جراحيا وتلى ذلك الحقن التجويفي لمنشط البلازمينوجين النسيجي المركب بجرعة ٢٥ ميكروغرام. كان هناك تشافي للالتهاب المستمر وتحسن كبير في حدة البصر في غضون أسبوع من الحقن. لم تُسجل أي تأثيرات جانبية في العين أو في الجسم. الحقن التجويفي لمنشط البلازمينوجين النسيجي المركب مفيد في المرضى الذين يعانون من التهاب القزحية الأمامية المتكرر بعد العملية الجراحية. في معظم الحالات، يكون التدخل الجراحي مهما لتوفير رؤية يستفيد منها المريض. يجب أن يؤخذ الحقن التجويفي لمنشط البلازمينوجين النسيجي المركب في الاعتبار عند التعامل مع الالتهابات المستمرة من أسباب مختلفة.\n\nالكلمات المفتاحية\nالتهاب البارتونيلا العينيفوت-كويناقي-هرادامنشط البلازمينوجين النسيجي المركبالتهاب القزحية الأمامية المتكررالتهاب الشبكيةKeywords\nOcular bartonellosisrtPARecalcitrant anterior uveitisRetinitisVogt–Koyanagi–Harada\n==== Body\nIntroduction\nCataracts and secondary refractory glaucoma are common complications of persistent chronic uveitis.1 In addition, extensive and severe fibrinous anterior-segment inflammation is common following cataract extraction and glaucoma surgeries in this particular condition. This sequelae is devastating for the patient and frustrating for the ophthalmologist. Topical or systemic steroid treatment can be ineffective and is often associated with unwanted side effects.2 Tissue plasminogen activator is a serine protease that activates the pro-enzyme plasminogen to form the active enzyme plasmin, which degrades fibrin into soluble products.3\n\nMany studies have shown that recombinant tissue plasminogen activator (rtPA) is effective and beneficial in the treatment of certain ocular diseases,4, 5, 6, 7, 8, 9, 10 and several reports have stated that severe anterior chamber fibrinous inflammation responds well to intracameral rtPA injection in steroid-resistant uveitis.6, 7 Intracameral rtPA injection was reported effective to resolve fibrin in two patients with HLA27-positive uveitis7 and post-operative endophthalmitis,8, 10 as well as in patients who have undergone cataract extraction4, 6 and glaucoma surgery.4, 5, 9 Other reports have claimed that intra-arterial or intravenous rtPA injection improves acute visual loss in central retinal artery occlusion11, 12, 13 and cilioretinal artery occlusion,14 and that intravitreal rtPA resolves massive pre-macular hemorrhage15 and sub-macular hemorrhage16 secondary to age-related macular degeneration, as well as total hyphema after penetrating injury.17 Intracameral injection is the main route of administration for treatment of anterior chamber fibrin reaction, although rtPA can also be delivered subconjunctivally.4\n\nTreatment of severe anterior chamber fibrin reaction after cataract or glaucoma surgery is a challenge in patients with pre-existing persistent uveitis. Persistent inflammation may lead to the formation of an anterior chamber fibrin membrane, which can further compromise the vision. In the present study, we evaluated the effect of intracameral rtPA injection on severe post-operative inflammation in two patients with recalcitrant anterior uveitis.\n\nCase reports\nCase 1\nA 40-year-old woman presented with a 2-week history of reduced vision, redness, glare, and discomfort in both eyes. She had no history of close contact with cats or dogs. Her best-corrected visual acuity (BCVA) was 6/7.5 in the right eye and 6/9 in the left eye. She had no relative afferent pupillary defect (RAPD). Examination revealed that both eyes had developed anterior chamber reaction, which was mild in the right eye and severe in the left eye. In both eyes, there were multiple keratic precipitates on the endothelium, as well as mild anterior vitreous cells. Both optic discs were hyperemic and swollen, showing retinitis, vasculitis, and macular edema. The intraocular pressure (IOP) was 13 mmHg in both eyes.\n\nInvestigations were conducted to establish the infectious or inflammatory causes of the patient's uveitis. Her serology was positive for Bartonella henselae IgM and IgG, as well as for Toxoplasma gondii IgG. She was treated for ocular bartonellosis and toxoplasmosis using oral doxycycline (100 mg) twice daily for 6 weeks and oral azithromycin (500 mg) daily for 6 weeks. Oral prednisolone was prescribed in a tapering dosage, with an initial daily dose of 35 mg. Topical prednisolone acetate (1%) and homatropine (2%) were administered 3 times daily. Systemic and topical steroids were used for 2 years to treat persistent inflammation, leading to seclusio pupillae, rubeosis iridis, and secondary cataracts in both eyes.\n\nDespite the treatment, the patient's vision had subsequently deteriorated to “counting fingers” (CF) at 2 feet in the right eye and to light perception in the left eye. Relative afferent pupillary defect (RAPD) was positive on her left eye, with iris neovascularization, and her left IOP ranged between 46 and 62 mmHg. An Ahmed valve was implanted in her left eye, and this procedure was combined with synechiolysis, peripheral iridectomy, and intracameral injection of triamcinolone (4 mg/0.1 mL). Intracameral ranibizumab (0.5 mg/0.05 mL) was injected prior to the procedures. Post-operatively, the patient's IOP was well-controlled: 12–16 mmHg during clinical follow-up.\n\nSubsequently, even though the patient was receiving maximum medication doses, her right eye's IOP started to increase. Therefore, a right-eye lens aspiration was performed, with implantation of a posterior chamber intraocular lens (PCIOL), synechiolysis, and intracameral injection of triamcinolone (4 mg/0.1 mL). After surgery, she developed severe inflammation, with blood clot, fibrin formation, and triamcinolone staining in the anterior chamber obscuring the pupil and intraocular lens (IOL) (Figure 1A). She was given two subconjunctival injections of dexamethasone (0.8 mg/0.2 mL) and mydricaine (1 mg atropine, 012 mg adrenaline and 6 mg procaine hydrochloride), but showed no improvement. She then underwent another procedure where her right anterior chamber was washed out, peripheral iridectomy was done and intracameral injection of dexamethasone was given. However, she still showed no improvement. An intracameral injection of rtPA (25 μg) was administered on day 17 after cataract extraction to treat the recalcitrant inflammation.Figure 1 Case 1: (A) Day 1 after cataract extraction with PCIOL implantation, synechiolysis, and intracameral triamcinolone. Note the dense fibrin membrane, blood clot, and triamcinolone staining in the anterior chamber covering the pupil and IOL (B) After rtPA injection. Note the complete resolution of the fibrin membrane, blood clot, and triamcinolone staining in the anterior chamber.\n\n\n\nThe fibrin membrane, blood clot, and triamcinolone staining had resolved 1 day after this injection, and the inflammation had resolved 3 days after the rtPA injection (Figure 1B). Her right eye best corrected visual acuity (BCVA) improved to 6/12. The tapering doses of oral prednisolone, topical prednisolone acetate (1%), topical homatropine (2%; 3 times daily), and topical moxifloxacin were continued.\n\nCase 2\nA healthy, 30-year-old man presented with reduced vision and redness without pain in both eyes, associated with tinnitus and headaches, that had persisted for 1 week. His BCVA was 6/18 in both eyes. Examination revealed bilateral conjunctival injection, granulomatous keratic precipitates, anterior chamber reaction (3+), and anterior vitreous cells (2+). Posteriorly, inferior exudative retinal detachment was noted, as were choroiditis, vitritis, Dalen–Fuchs nodules, macular edema with striae, and swollen and hyperemic optic discs. However, there was no RAPD. The patient showed mild sensorineural hearing loss in both ears. Otherwise, he had no poliosis, vitiligo, or alopecia. Serology was negative for antinuclear antibody, rheumatoid factor, toxoplasma, syphilis, toxocara, and cytomegalovirus, and the patient's renal function, complete blood count, erythrocyte sedimentation rate, Mantoux test, and chest radiograph were normal.\n\nBased on clinical findings, he was diagnosed with Vogt–Koyanagi–Harada (VKH) disease and treated using intravenous methylprednisolone (250 mg; 4 times daily) for 3 days, followed by tapering doses of oral prednisolone (50 mg daily), topical homatropine (2%; 3 times daily), and prednisolone acetate (1%) for 6 years. Anterior and posterior segment inflammation persisted, leading to bilateral neovascularization of the optic discs and subretinal hemorrhage, with vitreous hemorrhage in the right eye. Bilateral panretinal photocoagulation therapy was performed in both eyes. Bilateral rubeosis iridis, steroid-induced cataracts, and secondary glaucoma had developed, and RAPD was present in the left eye. His vision had deteriorated to “hand movement” in the right eye and CF at 2 feet in the left eye.\n\nFurthermore, he developed systemic side effects of steroids: moon facies, buffalo hump, and abdominal striae. To minimize the side effects of systemic steroid, oral cyclosporine (50 mg 2 times daily) was started. Even though he was receiving maximum medications for elevated IOP, his IOP was persistently high—ranging between 13 and 55 mmHg. A right augmented trabeculectomy with mitomycin C administration (0.04%; 0.4 mg), was performed to control his IOP. Initially, this procedure was successful, but the patient later showed signs of failure that necessitated needling with 5-fluorouracil (10 mg/0.2 mL). Subsequently, seclusio pupillae developed, and his IOP continued to rise, reaching 34–48 mmHg. A Baerveldt valve was then implanted, combined with mitomycin C administration (0.2%; 0.2 mg), phacoemulsification, PCIOL implantation, and synechiolysis. His IOP was reduced to 8–20 mm Hg.\n\nAn Ahmed valve was then implanted in his left eye, combined with mitomycin C (0.04%; 0.4 mg), phacoemulsification, and PCIOL implantation. Due to uncontrolled IOP in the left eye, a second glaucoma drainage device was implanted in the superior temporal region 2 years later. To reduce the complications associated with rubeosis iridis, intravitreal ranibizumab (0.5 mg/0.05 mL) was injected into both eyes 1 week prior to surgical intervention.\n\nInflammation persisted despite the systemic and topical anti-inflammatory drugs (oral prednisolone, oral cyclosporine, and topical prednisolone acetate [1%]), leading to seclusio pupillae and a severe anterior chamber fibrin membrane on the right eye. The fibrin membrane formation slowly progressed to cover the visual axis and IOL, causing deterioration of vision to CF at 2 feet. At this point, the patient was housebound, but still able to care for himself. Four years later, to help improve his vision, right eye synechiolysis, membrane excision, and intracameral rtPA injection (25 μg) were performed after cataract extraction and glaucoma surgery. After surgery, the membrane was completely resolved, and only minimal posterior synechiae remained (Figure 2). His BCVA improved to 6/21 in the right eye and 6/7.5 in the left eye.Figure 2 Case 2: 12 h after rtPA injection. Note the fibrin membrane dissolution, with minimal membrane and posterior synechiae remaining.\n\n\n\nDiscussion\nIt is challenging and frustrating to deal with persistent ocular inflammation—every possible decision has a high risk of complications and a low chance of success. However, with advances in technology and drug development, the management of persistent and recalcitrant ocular inflammation has become more rewarding.\n\nIn the two cases of the present report, we observed significant improvement in visual acuity 1 week after intracameral rtPA injection. In fact, in cases 1 and 2, fibrin had completely resolved on days 3 and 1 after rtPA injection, respectively. Other studies have reported that fibrin completely resolves as early as 30 min to several hours after rtPA injection.4, 7\n\nHowever, intracameral rtPA injection is not recommended to treat anterior segment fibrin clots that have persisted for more than 20 days.18 Moreover, rtPA should be injected 4 days to 3 weeks after surgery to ensure maximal benefit and minimal risk of bleeding from clot lysis.4 However, in case 2, rtPA injection was performed 4 years after surgery for cataract extraction, PCIOL implantation, and glaucoma. To our knowledge, no previous studies have reported intracameral rtPA injection years after anterior chamber surgery. The patient in case 2 benefited from rtPA injection several years after anterior segment surgery in steroid resistant and recalcitrant uveitis.\n\nIn both cases, rtPA injection was carried out to reduce fibrin exudation and improve visual acuity after anterior segment surgery. To date, the dosage of intracameral rtPA injection in uveitis has not been standardized. We selected a dosage of 25 μg of rtPA based on previous studies.5, 8, 10, 17 Both Damji et al. and Riaz et al. reported complete fibrin resolution after intracameral rtPA injection (25 μg) in patients with pseudophakic endophthalmitis who had severe anterior chamber fibrin reaction. A lower concentration of rtPA has been reported to be equally effective. For example, Heiligenhaus et al. reported that anterior chamber fibrin resolved in a patient with uveitis after intracameral injection of 10 μg rtPA. Additionally, intracameral injection of 12.5 μg rtPA resolved a severe anterior chamber fibrin reaction in HLA27-positive uveitis patients.7\n\nThere were no complications related to rtPA injection in either case, although such complications are not uncommon and include anterior chamber bleeding, transient clouding of cornea, anterior chamber flattening, and hypotony.4, 5, 9, 19 Lundy et al. reported that hyphema was more likely to occur after intracameral injection of 25 μg rtPA to treat severe fibrin formation after glaucoma surgery with or without cataract extraction.\n\nTo conclude, rtPA injection is effective as an adjunctive treatment for severe post-operative inflammation in recalcitrant anterior uveitis. This treatment should be considered in the treatment of persistent inflammation of varying etiology.\n\nSource of funding\nNone.\n\nConflict of interest\nThe authors have no conflict of interest to declare.\n\nConsent\nInformed consent was obtained from all patients.\n\nAuthors' contributions\nAll authors contributed to patient management, literature review, and preparation of the manuscript. All authors read and approved the final manuscript. All authors have critically reviewed and approved the final draft and are responsible for the content and similarity index of the manuscript.\n\nPeer review under responsibility of Taibah University.\n==== Refs\nReferences\n1 Menezo V. Lightman S. The development of ccomplications in patients with chronic uveitis Am J Ophthalmol 139 6 2005 988 992 15953427 \n2 Renfro L. Snow J.S. Ocular effects of topical and systemic steroids Dermato Clin 10 3 1992 505 512 \n3 Lijnen H.R. Collen D. 1 Mechanisms of physiological fibrinolysis Bailliere Clin Haematol 8 2 1995 277 290 \n4 Tripathi R.C. Tripathi B.J. Bornstein S. Gabianelli E. Ernest J.T. Use of tissue plasminogen activator for rapid dissolution of fibrin and blood clots in the eye after surgery for glaucoma and cataract in humans Drug Dev Res 27 2 1992 147 159 \n5 Lundy D.C. Sidoti P. Winarko T. Minckler D. Heuer D.K. Intracameral tissue plasmmogen activator after glaucoma surgery: indications, effectiveness, and complications Ophthalmology 103 2 1996 274 282 8594514 \n6 Heiligenhaus A. Steinmetz B. Lapuente R. Krallmann P. Althaus C. Steinkamp W. Recombinant tissue plasminogen activator in cases with fibrin formation after cataract surgery: a prospective randomised multicentre study Br J Ophthalmol 82 7 1998 810 815 9924378 \n7 Skolnick C.A. Fiscella R.G. Tessler H.H. Goldstein D.A. Tissue plasminogen activator to treat impending pupillary block glaucoma in patients with acute fibrinous HLA-B27 positive iridocyclitis Am J Ophthalmol 129 3 2000 363 366 10704553 \n8 Damji K.F. O'Connor M.D. Hill V. Tissue plasminogen activator for treatment of fibrin in endophthalmitis Can J Ophthalmology 36 5 2001 269 271 \n9 Zalta A.H. Sweeney C.P. Zalta A.K. Kaufman A.H. Intracameral tissue plasminogen activator use in a large series of eyes with valved glaucoma drainage implants Arch Ophthalmol 120 11 2002 1487 1493 12427061 \n10 Riaz Y. Mehta J.S. Fernando A. Ferguson V. Recombinant tissue plasminogen activator (r-TPA) in fibrin dissolution due to postoperative endophthalmitis Ann Acad Med Singapore 35 10 2006 723 17102897 \n11 Richard G. Lerche R.-C. Knospe V. Zeumer H. Treatment of retinal arterial occlusion with local fibrinolysis using recombinant tissue plasminogen activator Ophthalmology 106 4 1999 768 773 10201601 \n12 Hattenbach L.-O. Kuhli-Hattenbach C. Scharrer I. Baatz H. Intravenous thrombolysis with low-dose recombinant tissue plasminogen activator in central retinal artery occlusion Am J Ophthalmol 146 5 2008 700–706.e1 \n13 Nowak R.J. Amin H. Robeson K. Schindler J.L. Acute central retinal artery occlusion treated with intravenous recombinant tissue plasminogen activator J Stroke Cerebrovasc Dis 21 8 2012 913. e5-. e8 \n14 McClellan A.J. Flynn H.W. Peterson E.C. Schatz N.J. Reversal of cilioretinal artery occlusion with intra-arterial tissue plasminogen activator Am J Ophthalmol Case Rep 7 Supplement C 2017 138 139 29260099 \n15 Wu T.-T. Kung Y.-H. Lin C.-S. Non-vitrectomizing vitreous surgery and adjuvant intravitreal tissue plasminogen activator for non-recent massive premacular hemorrhage J Chin Med Assoc 74 12 2011 574 578 22196475 \n16 Tsai S.-C. Lin J.-M. Chen H.-Y. Intravitreous recombinant tissue plasminogen activator and gas to treat submacular hemorrhage in age-related macular degeneration Kaohsiung J Med Sci 19 12 2003 608 615 14719558 \n17 Laatikainen L. Mattila J. The use of tissue plasminogen activator in post-traumatic total hyphaema Graefe's Arch Clin Exp Ophthalmol 234 1 1996 67 68 8750854 \n18 Folk J.C. Hershey J.M. Rivers M.B. Lack of effectiveness of tissue plasminogen activator 20 or more days after vitrectomy Arch Ophthalmol 109 5 1991 614- \n19 Rehfeldt K. Höh H. Therapeutic and prophylactic application of TPA (recombinant tissue plasminogen activator) into the anterior chamber of the eye Ophthalmologe 96 9 1999 587 593 10501987\n\n", "fulltext_license": "CC BY-NC-ND", "issn_linking": "1658-3612", "issue": "13(5)", "journal": "Journal of Taibah University Medical Sciences", "keywords": "Ocular bartonellosis; Recalcitrant anterior uveitis; Retinitis; Vogt–Koyanagi–Harada; rtPA", "medline_ta": "J Taibah Univ Med Sci", "mesh_terms": null, "nlm_unique_id": "101621911", "other_id": null, "pages": "483-487", "pmc": null, "pmid": "31435366", "pubdate": "2018-10", "publication_types": "D002363:Case Reports", "references": "10201601;10501987;10704553;11548143;12427061;14719558;15953427;1617809;17102897;18718570;1902660;22196475;22349707;29260099;7549063;8594514;8750854;9924378", "title": "Use of recombinant tissue plasminogen activator for treatment of recalcitrant anterior uveitis: A case series.", "title_normalized": "use of recombinant tissue plasminogen activator for treatment of recalcitrant anterior uveitis a case series" }

[ { "companynumb": "MY-BAUSCH-BL-2018-028086", "fulfillexpeditecriteria": "1", "occurcountry": "MY", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE ACETATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "40070", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOGT-KOYANAGI-HARADA SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE ACETATE 1 PERCENT" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "75250", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "TAPERING DOSES OF PREDNISOLONE", "drugenddate": null, "drugenddateformat": null, "drugindication": "VOGT-KOYANAGI-HARADA SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOGT-KOYANAGI-HARADA SYNDROME", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "6", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "5", "activesubstance": null, "drugadditional": "3", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOGT-KOYANAGI-HARADA SYNDROME", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HOMATROPINE 2 PERCENT" } ], "patientagegroup": null, "patientonsetage": "30", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cushingoid", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Skin striae", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cataract", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Lipohypertrophy", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PATRICK S, HUI-TZE C, WAN-HAZABBAH W, ZUNAINA E, AZHANY Y, LIZA-SHARMINI A. USE OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR FOR TREATMENT OF RECALCITRANT ANTERIOR UVEITIS: A CASE SERIES. JOURNAL OF TAIBAH UNIVERSITY MEDICAL SCIENCES. 2018?13(5):483-487.", "literaturereference_normalized": "use of recombinant tissue plasminogen activator for treatment of recalcitrant anterior uveitis a case series", "qualification": "1", "reportercountry": "MY" }, "primarysourcecountry": "MY", "receiptdate": "20181019", "receivedate": "20181019", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15531538, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" }, { "companynumb": "MY-TEVA-2018-MY-968762", "fulfillexpeditecriteria": "1", "occurcountry": "MY", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "080354", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "35 MILLIGRAM DAILY; IN A TAPERED DOSAGE", "drugenddate": null, "drugenddateformat": null, "drugindication": "IRIDOCYCLITIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "35", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE ACETATE" }, "drugadditional": null, "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "FOR 2 YEARS", "drugenddate": null, "drugenddateformat": null, "drugindication": "IRIDOCYCLITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE ACETATE 1 %" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TRIAMCINOLONE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4 MG/0.1 ML", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TRIAMCINOLONE" }, { "actiondrug": "4", "activesubstance": null, "drugadditional": null, "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IRIDOCYCLITIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HOMATROPINE 2%" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DOXYCYCLINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXYCYCLINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AZITHROMYCIN ANHYDROUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZITHROMYCIN ANHYDROUS." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "MOXIFLOXACIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOXIFLOXACIN." } ], "patientagegroup": null, "patientonsetage": "40", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cataract", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Foreign body in eye", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PATRICK S, HUI-TZE C, WAN-HAZABBAH WH, ZUNAINA E, AZHANY Y, LIZA-SHARMINI AT. USE OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR FOR TREATMENT OF RECALCITRANT ANTERIOR UVEITIS: A CASE SERIES. J-TAIBAH-UNIV-MED-SCI 2018?13(5):483-487.", "literaturereference_normalized": "use of recombinant tissue plasminogen activator for treatment of recalcitrant anterior uveitis a case series", "qualification": "1", "reportercountry": "MY" }, "primarysourcecountry": "MY", "receiptdate": "20181025", "receivedate": "20181025", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15549146, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" }, { "companynumb": "MY-MYLANLABS-2018M1078841", "fulfillexpeditecriteria": "1", "occurcountry": "MY", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "061", "drugauthorizationnumb": "202179", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IRIDOCYCLITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "202179", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "IN A TAPERED DOSAGE", "drugenddate": null, "drugenddateformat": null, "drugindication": "IRIDOCYCLITIS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "35", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DOXYCYCLINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXYCYCLINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MOXIFLOXACIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MOXIFLOXACIN." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "HOMATROPINE\\HOMATROPINE HYDROBROMIDE" }, "drugadditional": null, "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "3 TIMES DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "IRIDOCYCLITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HOMATROPINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TRIAMCINOLONE" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "4 MG/0.1 ML", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TRIAMCINOLONE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZITHROMYCIN ANHYDROUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZITHROMYCIN ANHYDROUS." } ], "patientagegroup": null, "patientonsetage": "40", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cataract", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Foreign body in eye", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PATRICK S, HUI-TZE C, WAN-HAZABBAH WH, ZUNAINA E, AZHANY Y, LIZA-SHARMINI AT. USE OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR FOR TREATMENT OF RECALCITRANT ANTERIOR UVEITIS: A CASE SERIES. J-TAIBAH-UNIV-MED-SCI 2018?13(5):483-487.", "literaturereference_normalized": "use of recombinant tissue plasminogen activator for treatment of recalcitrant anterior uveitis a case series", "qualification": "1", "reportercountry": "MY" }, "primarysourcecountry": "MY", "receiptdate": "20181029", "receivedate": "20181029", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15561922, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" }, { "companynumb": "MY-TEVA-2018-MY-968761", "fulfillexpeditecriteria": "1", "occurcountry": "MY", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "080354", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "VOGT-KOYANAGI-HARADA SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE ACETATE" }, "drugadditional": "3", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOGT-KOYANAGI-HARADA SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE ACETATE 1%" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "VOGT-KOYANAGI-HARADA SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "4", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "5", "activesubstance": null, "drugadditional": "3", "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOGT-KOYANAGI-HARADA SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HOMATROPINE 2%" } ], "patientagegroup": null, "patientonsetage": "30", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Glaucoma", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Lipohypertrophy", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Skin striae", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cushingoid", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cataract", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PATRICK S, HUI-TZE C, WAN-HAZABBAH WH, ZUNAINA E, AZHANY Y, LIZA-SHARMINI AT. USE OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR FOR TREATMENT OF RECALCITRANT ANTERIOR UVEITIS: A CASE SERIES. J-TAIBAH-UNIV-MED-SCI 2018?13(5):483-487.", "literaturereference_normalized": "use of recombinant tissue plasminogen activator for treatment of recalcitrant anterior uveitis a case series", "qualification": "1", "reportercountry": "MY" }, "primarysourcecountry": "MY", "receiptdate": "20181025", "receivedate": "20181025", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15549315, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" }, { "companynumb": "MY-ALLERGAN-1849458US", "fulfillexpeditecriteria": "1", "occurcountry": "MY", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "047", "drugauthorizationnumb": "017100", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": "INFLAMMATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE UNK" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "HOMATROPINE HYDROBROMIDE" }, "drugadditional": null, "drugadministrationroute": "061", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": "INFLAMMATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HOMATROPINE" } ], "patientagegroup": null, "patientonsetage": "40", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Iris neovascularisation", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Visual acuity reduced", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pupillary block", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Intraocular pressure increased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cataract", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PATRICK S, HUITZE C, WANHAZABBAH WH, ZUNAINA E, AZHANY Y, LIZA SHARMINI AT. USE OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR FOR TREATMENT OF RECALCITRANT ANTERIOR UVEITIS: A CASE SERIES. JOURNAL OF TAIBAH UNIVERSITY MEDICAL SCIENCE. 2018?13(5):483?487", "literaturereference_normalized": "use of recombinant tissue plasminogen activator for treatment of recalcitrant anterior uveitis a case series", "qualification": "3", "reportercountry": "MY" }, "primarysourcecountry": "MY", "receiptdate": "20181017", "receivedate": "20181017", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15519771, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201104" } ]

{ "abstract": "Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia in cancer patients. It is most frequently reported in association with small-cell lung cancer, but has been reported in other cancers as well. Here we report the case of a patient with myelodysplastic syndrome and blast crisis who developed concurrent hyponatremia. The patient failed to respond to fluid restriction and administration of hypertonic saline. She was treated with tolvaptan, a vasopressin antagonist licensed for the treatment of adult patients with hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion. We conclude that in myelodysplastic syndrome patients with blast crisis, inappropriate antidiuretic hormone secretion should be considered as a cause of hyponatremia and be treated with tolvaptan.", "affiliations": null, "authors": "Mali|Padmavathi|P|;Muduganti|Sudheer R|SR|;Mujibur|Rahaman|R|;Murali|Narayana|N|", "chemical_list": "D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan", "country": "United States", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "1098-1861", "issue": "114(2)", "journal": "WMJ : official publication of the State Medical Society of Wisconsin", "keywords": null, "medline_ta": "WMJ", "mesh_terms": "D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D001752:Blast Crisis; D005260:Female; D006801:Humans; D007177:Inappropriate ADH Syndrome; D009190:Myelodysplastic Syndromes; D000077602:Tolvaptan", "nlm_unique_id": "9716054", "other_id": null, "pages": "66-8", "pmc": null, "pmid": "26756059", "pubdate": "2015-04", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Tolvaptan for SIADH in Myelodysplastic Syndrome with Blast Crisis.", "title_normalized": "tolvaptan for siadh in myelodysplastic syndrome with blast crisis" }

[ { "companynumb": "US-CELGENE-USA-2015054035", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "AZACITIDINE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "050794", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "MYELODYSPLASTIC SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VIDAZA" } ], "patientagegroup": null, "patientonsetage": "66", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Inappropriate antidiuretic hormone secretion", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MALI P. TOLVAPTAN FOR SIADH IN MYELODYSPLASTIC SYNDROME WITH BLAST CRISIS.. WISCONSIN MEDICAL JOURNAL. 2015 APR 01;114 (2):66-68.", "literaturereference_normalized": "tolvaptan for siadh in myelodysplastic syndrome with blast crisis", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150605", "receivedate": "20150605", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11168193, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150821" } ]

{ "abstract": "BACKGROUND\nConventional treatment of interstitial pregnancies includes systemic methotrexate, direct methotrexate injection, wedge resection, or hysterectomy. We present two cases of interstitial pregnancies that were successfully managed by different minimally invasive surgical techniques. We also report the novel use of hysteroscopic urologic stone retrieval forceps in the transvaginal removal of persistent products of conception after systemic methotrexate for an interstitial pregnancy.\n\n\nMETHODS\nCase 1 was a 28-year-old gravida 1 white woman at 8 weeks gestation; she was diagnosed with a left interstitial pregnancy. After laparoscopic confirmation of the interstitial pregnancy, successful ultrasound-guided suction dilation and curettage was performed. Case 2 was a 33-year-old gravida 3 para 1021 (one term pregnancy, no preterm pregnancies, one ectopic pregnancy and one spontaneous miscarriage, and one living child) Hispanic woman with persistent products of conception after systemic methotrexate for a left interstitial pregnancy. She underwent hysteroscopic-guided removal of the persistent products of conception, which was possible due to novel use of urologic stone retrieval forceps.\n\n\nCONCLUSIONS\nSuccessful minimally invasive treatment of interstitial pregnancies may be possible in certain cases. Collaboration between different specialties continues to be important for improving minimally invasive options.", "affiliations": "Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Colorado Denver School of Medicine, Aurora, CO, USA. natalia.grindler@ucdenver.edu.;University of Colorado Denver School of Medicine, Aurora, CO, USA.;University of Colorado Denver School of Medicine, Aurora, CO, USA.;Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Colorado Denver School of Medicine, Aurora, CO, USA.", "authors": "Grindler|Natalia M|NM|;Ng|June|J|;Tocce|Kristina|K|;Alvero|Ruben|R|", "chemical_list": "D000020:Abortifacient Agents, Nonsteroidal; D008727:Methotrexate", "country": "England", "delete": false, "doi": "10.1186/s13256-016-0892-9", "fulltext": "\n==== Front\nJ Med Case RepJ Med Case RepJournal of Medical Case Reports1752-1947BioMed Central London 89210.1186/s13256-016-0892-9Case ReportConsiderations for management of interstitial ectopic pregnancies: two case reports Grindler Natalia M. natalia.grindler@ucdenver.edu Ng June june.ng@ucdenver.edu Tocce Kristina kristina.tocce@ucdenver.edu Alvero Ruben ralvero@wihri.org Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Colorado Denver School of Medicine, Aurora, CO USA University of Colorado Denver School of Medicine, Aurora, CO USA Division of Family Planning, Department of Obstetrics and Gynecology, University of Colorado Denver School of Medicine, Aurora, CO USA Division of Reproductive Endocrinology & Infertility, Department of Obstetrics and Gynecology, Warren P. Alpert School of Medicine, Brown University, Providence, RI USA 27 4 2016 27 4 2016 2016 10 10614 9 2015 1 4 2016 © Grindler et al. 2016\nOpen AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background\nConventional treatment of interstitial pregnancies includes systemic methotrexate, direct methotrexate injection, wedge resection, or hysterectomy. We present two cases of interstitial pregnancies that were successfully managed by different minimally invasive surgical techniques. We also report the novel use of hysteroscopic urologic stone retrieval forceps in the transvaginal removal of persistent products of conception after systemic methotrexate for an interstitial pregnancy.\n\nCase presentation\nCase 1 was a 28-year-old gravida 1 white woman at 8 weeks gestation; she was diagnosed with a left interstitial pregnancy. After laparoscopic confirmation of the interstitial pregnancy, successful ultrasound-guided suction dilation and curettage was performed. Case 2 was a 33-year-old gravida 3 para 1021 (one term pregnancy, no preterm pregnancies, one ectopic pregnancy and one spontaneous miscarriage, and one living child) Hispanic woman with persistent products of conception after systemic methotrexate for a left interstitial pregnancy. She underwent hysteroscopic-guided removal of the persistent products of conception, which was possible due to novel use of urologic stone retrieval forceps.\n\nConclusions\nSuccessful minimally invasive treatment of interstitial pregnancies may be possible in certain cases. Collaboration between different specialties continues to be important for improving minimally invasive options.\n\nKeywords\nCornual pregnancyInterstitial pregnancyEctopic pregnancyPersistent products of conceptionMinimally invasive surgeryissue-copyright-statement© The Author(s) 2016\n==== Body\nBackground\nA cornual ectopic pregnancy is defined as a gestation that occurs within the endometrium of the horn of a unicornuate or bicornuate uterus, whereas an interstitial pregnancy occurs within the uterus at the junction of the uterus and the proximal part of the fallopian tube [1–3]. Interstitial pregnancy occurs when implantation occurs in the most proximal section of the tube surrounded by the myometrium. This interstitial portion of the fallopian tube is highly vascular; rupture results in excessive intraperitoneal hemorrhage. Although these pregnancies represent approximately 2 to 4 % of all ectopic pregnancies, maternal mortality is high (2 % of cases) due to the risk of uterine rupture and subsequent hemorrhagic shock [1–4]. The routine use of early ultrasonography has enabled the development of minimally invasive surgical techniques before serious complications occur. The diagnosis of an interstitial pregnancy can be made based on the following ultrasound criteria: empty uterine cavity, a chorionic sac separate and at least 1 cm from the lateral edge of the uterine cavity, and a thin (<5 mm) myometrial layer surrounding the gestational sac [1, 5]. Risk factors for an interstitial pregnancy are similar to those for any ectopic pregnancy: pelvic inflammatory disease, previous tubal surgery, previous ectopic pregnancy, assisted reproductive technology, and congenital uterine anomalies. Ipsilateral salpingectomy is the only risk factor that exists exclusively for interstitial pregnancy [2].\n\nConventional treatment for interstitial pregnancies includes systemic methotrexate, cornual wedge resection, or hysterectomy. With the advancement of ultrasound and minimally invasive techniques, other management options now include direct injection of methotrexate into the abnormal pregnancy, combined systemic and direct injection technique [6], and laparoscopic cornual wedge resection. To the best of our knowledge, there have been no cases reported of tubal rupture from persistent products of conception (POC) in an interstitial pregnancy after surgical treatment or methotrexate. However, given the potential risk of uterine rupture with associated high mortality and morbidity, persistent POC pose a potential threat to a woman’s future fertility and overall health. We present two cases of interstitial pregnancies that were successful managed by different minimally invasive surgical techniques.\n\nCase presentation\nCase 1\nA 28-year-old gravida 1 para 0 white woman with a past medical history significant for polycystic ovarian syndrome and a history of laparoscopic gastric bypass surgery, presented to our emergency department with vaginal bleeding. She reported clomiphene citrate use and was 8 weeks 6 days pregnant by last menstrual period. She had a benign pelvic examination. Her beta hCG level was 39,745 mIU/mL. A transvaginal ultrasound revealed an eccentrically located gestational sac with 3 mm of myometrium in the left posterior cornu. A yolk sac and embryo with a crown-rump length (CRL) of 6.2 mm were also seen but no fetal cardiac activity was demonstrated. The diagnoses of probable early pregnancy loss (EPL) and interstitial location of the pregnancy were explained to the patient. As this was a highly desired pregnancy, she declined intervention and elected for expectant out-patient management. Subsequent follow-up ultrasound 48 hours later demonstrated a CRL of 7 mm without cardiac activity and 3 mm of myometrium in the thickness area, posterior to the sac. The diagnosis of EPL of an interstitial pregnancy based on CRL >7 mm without fetal cardiac activity was discussed with her. She was counseled on all available management options including expectant and medical management. She elected to proceed with surgical management and gave consent for the following potential procedures: examination under anesthesia, dilation and curettage (D&C), diagnostic laparoscopy, possible operative laparoscopy, possible exploratory laparotomy, possible cornual wedge resection with salpingectomy, and possible hysterectomy. She was informed that D&C is not the standard treatment modality for interstitial pregnancies. However, after a family planning specialist and a radiologist reviewed her images, it was felt that the inferior aspect of the sac might be accessible with a cannula angled towards the cornua. Since this was an EPL, pre-procedure methotrexate was not offered because there was no evidence indicating that it would facilitate removal.\n\nLaparoscopic confirmation of her interstitial pregnancy was performed first to ensure that no interval interstitial rupture had occurred. Laparoscopy revealed the left cornu of her uterus to be thin and tensely distended with a gestational sac; a large blood vessel was seen overlying the cornu (Fig. 1). Her cervix was then dilated to 7 mm and a 7 mm flexible cannula was placed just inferior to the gestational sac under direct ultrasound guidance. Manual vacuum aspiration was performed and the POC were removed with two passes. Afterwards, her uterus appeared completely normal on laparoscopic visualization (Fig. 1). She tolerated the procedure well and was discharged home on the same day without further complications. Pathology was consistent with POC. Postoperative beta hCG were monitored weekly until <5 mIU/mL.Fig. 1 Laparoscopic intraoperative images of Case 1. a The left cornu of the uterus is thin and tensely distended with a gestational sac. b The left cornu after manual vacuum aspiration of abnormal pregnancy\n\n\n\nCase 2\nA 33-year-old gravida 3 para 1021 (one term pregnancy, no preterm pregnancies, one ectopic pregnancy and one spontaneous miscarriage, and one living child) Hispanic woman with a history of a previously diagnosed cornual ectopic pregnancy in a unicornuate uterus presented for evaluation and treatment of suspected persistent POC in the left cornu of a unicornuate uterus. Her pregnancy history is notable for a term uncomplicated vaginal delivery and prior early first trimester miscarriage managed with expectant management. She had no other significant medical or surgical history. She was diagnosed with a left interstitial pregnancy and treated with systemic methotrexate, receiving a total of four doses. Given her desire to conceive again, she underwent a gynecologic ultrasound, which revealed a persistent gestational sac and fetal pole in the left cornu despite multiple confirmatory hCG values <5. She was asymptomatic but was referred to the reproductive endocrinology service for management of this residual mass given her desire to try to conceive again and the potential to utilize assisted reproductive technology in future cycles. Ultrasound revealed a gestational sac in the left cornu measuring 10×7 mm with generalized reactive muscular echogenicity surrounding the sac and a fetal pole measuring 6.2 mm (Fig. 2). Ultrasound findings were suggestive that these persistent POC would be accessible via suction D&C based on its continuity with the endometrial stripe on ultrasound.Fig. 2 Intraoperative transabdominal ultrasound of Case 2. a Interstitial ectopic pregnancy with a gestational sac in the left cornu and generalized reactive muscular echogenicity surrounding the sac. b) After successful hysteroscopic removal, the decidualized reaction in the left cornu resolves. POC products of conception\n\n\n\nShe was counseled regarding the following options: further expectant management with serial ultrasound monitoring given no known evidence that persistent POC can result in uterine rupture, and surgery. She elected to proceed with definitive surgical treatment given her desire to conceive and the potential catastrophic nature of uterine rupture in her unicornuate uterus. Intraoperative transvaginal and transabdominal ultrasound again confirmed persistent left interstitial pregnancy with POC within surrounding decidualized endometrium. A family planning specialist was consulted during this case. First, suction D&C was attempted. A 7 mm flexible cannula was inserted to the fundus under transvaginal ultrasound guidance. The left cornu was unable to be accessed despite multiple attempts with transabdominal and transvaginal ultrasound guidance. This was also attempted with a 7 mm rigid curved cannula but similarly was unsuccessful.\n\nHysteroscopy was then performed using a 5 mm Karl Storz operative hysteroscope with a 2.9 mm 30° lens, 5mm sheath, and 5-Fr operating port with normal saline as the distending media. Upon entry of the hysteroscope into her uterus, tubal ostium was identified. However, no gross POC were visualized within her uterine cavity. Next, a Novy™ Cornual Cannulation Set (Cook Medical) was passed hysteroscopically into the left cornual region under hysteroscopic and ultrasound guidance (Fig. 3). Although the device was successfully cannulated into the left cornu, no tissue was able to be aspirated (Fig. 4). As an alternative intended to grasp and remove the POC, a Tricep™ extra-strength hooked-prong grasping forceps (Boston Scientific) with a 3.0-Fr sheath and 120-cm working length (urologic stone retrieval basket) was suggested based on prior cornual procedures with a similar device [7]. This device was placed into the left cornu under both hysteroscopic and ultrasound guidance (Fig. 3); it was opened and closed within the cornual region several times. Dense fibrous tissue was grasped and removed with visible POC. This was repeated several times in a similar fashion. Karl Storz 5-Fr hysteroscopic grasping forceps were also used to grasp tissue extruding from this cornu several times (Fig. 5). At the end of the case, ultrasound revealed resolution of the myometrial decidual reaction with removal of persistent POC (Fig. 2). Safety was assured during the case with constant hysteroscopic visualization; transabdominal ultrasonography was also utilized to assure excellent visualization at all times. Laparoscopy was not necessary in this case due to combined hysteroscopic and ultrasonographic visualization during the case. The patient was counseled that the resolution of the persistent POC on ultrasound and hysteroscopy decreased the risk of uterine rupture but she was cautioned regarding the continued potential for rupture. Pathology revealed fragments of necrotic chorionic villi and decidua. She was discharged home the same day and had an uncomplicated postoperative course. Postoperative beta hCG was measured again postoperatively and was <5 mIU/mL.Fig. 3 \na Novy™ Cornual Cannulation Set (Cook Medical) with 5.0-Fr sheath and 0.46 mm guide wire diameter and b Tricep™ extra-strength hooked-prong grasping forceps (Boston Scientific) with a 3.0-Fr sheath and 120-cm working length (urologic stone retrieval basket) utilized for management in Case 2\n\nFig. 4 Hysteroscopic visualization of persistent products of conception from within the cornu after treatment with systemic methotrexate for cornual ectopic pregnancy in Case 2\n\nFig. 5 Persistent products of conception being removed from the cornu with the use of urologic stone retrieval forceps in Case 2\n\n\n\nDiscussion\nCornual and interstitial pregnancies are rare types of ectopic pregnancies, but remain a significant cause of maternal morbidity and mortality. In our first case, collaboration between a radiologist and a family planning specialist resulted in the successful resolution of an interstitial pregnancy with the use of ultrasound-guided suction D&C. A flexible cannula was chosen in order to minimize the risk of cornual perforation. With this instrument, the cornu did not need to be directly instrumented (the cannula was placed just inferior to the sac) and the manual vacuum aspiration suction minimized potential trauma to the cornu because as the device fills with tissue, the force of the suction decreases.\n\nOur second case resulted in collaboration between family planning and reproductive endocrinology specialists and led to the successful resolution of persistent cornual POC. Hysteroscopic-guided curettage using urologic instruments was utilized in this case. The presence of the cornual abnormality, which could be detected both by ultrasound and hysteroscopically in our second case, dictated the need to remove the tissue for histologic evaluation. Her undetectable hCG was probably due to the necrotic nature of the chorionic villi which was confirmed histologically. The cornu was normalized by the conclusion of the case and the patient currently has an ongoing normal pregnancy. In both cases, interstitial pregnancies were successfully managed with minimally invasive techniques that were fertility-preserving surgical techniques, which resulted in minimal blood loss, preserved reproductive organs, and a probable return to normal reproductive function. Advanced minimally invasive techniques and innovative approaches to management of the unruptured interstitial pregnancy in our patients resulted in optimal immediate postoperative outcomes.\n\nThere is no general consensus on the best surgical procedure for interstitial ectopic pregnancy. Medical treatment with methotrexate has been associated with a failure rate ranging from 9 to 65 % [3, 8–10] and the best medical treatment regimen for interstitial pregnancy remains unknown. Increasingly more conservative approaches are being used due to the proliferation of minimally invasive gynecological surgery and advanced surgical techniques. Our criteria for offering minimally invasive surgical techniques include the following: hemodynamic stability and no evidence of uterine rupture. Although successful hysteroscopic management of interstitial pregnancies has previously been reported [11], we believe that our novel utilization of urologic forceps has the potential to be applied to similar and related cases. Use of a 8F pediatric catheter has been reported for transcervical suction of POC in interstitial pregnancies while under laparoscopic visualization; however, at least two cases utilizing this technique have resulted in cornual perforation [12]. Similarly, use of hysteroscopic polyp forceps under ultrasound guidance resulted in incomplete extraction and postoperative methotrexate was required [13]. Other minimally invasive techniques described for management of interstitial pregnancies include laparoscopic-guided transcervical evacuation [14], laparoscopic-guided use of a resectoscope [15], ipsilateral uterine artery ligation at the time of cornual repair [16, 17], and the use of end loop and encircling sutures at the cornua [16, 18–20]. Our cases highlight the importance of collaboration between different medical specialties in these challenging rare clinical cases as well as the importance of attempting novel techniques in appropriately selected patients when the alternative would result in unnecessary additional risk for the patient.\n\nAs is the case for all novel minimally invasive techniques, the surgeon should be ready to perform cornual resection with salpingectomy or hysterectomy if uterine perforation occurs. The risk of uterine rupture during subsequent pregnancies in patients who have been previously treated for an interstitial pregnancy has not been clearly established [3]. Although the exact risk of uterine rupture in subsequent pregnancy is unknown, women should be counseled carefully about this possibility as uterine rupture has occurred in patients with previous treatments for interstitial pregnancies [21, 22]. These cases highlight that interstitial pregnancies can be managed with minimally invasive procedures in properly selected patients.\n\nConclusions\nIn this case report, we present two cases of interstitial pregnancies that were successfully managed with minimally invasive techniques, including the novel use of hysteroscopic urologic stone retrieval forceps to remove retained cornual tissue. The approaches utilized in these cases were the result of collaboration between subspecialties, with the goal of preserving fertility that was strongly desired by these patients. Subsequent pregnancies should be closely monitored because of the risks of recurrent ectopic pregnancy and theoretical uterine rupture. Whenever possible, non-invasive management of interstitial pregnancies should be attempted. Success leads to better immediate and possible future outcomes that are important for the reproductive health of our patients.\n\nConsent\nWritten informed consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consents is available for review by the Editor-in-Chief of this journal.\n\nAbbreviations\nCRLcrown-rump length\n\nD&Cdilation and curettage\n\nEPLearly pregnancy loss\n\nPOCproducts of conception\n\nCompeting interests\n\nThe authors declare that they have no competing interests.\n\nAuthors’ contributions\n\nNG, KT, and RA were involved in the surgical management and treatment for these cases. NG, JN, and KT were major contributors in writing the manuscript. All authors read and approved the final manuscript.\n\nAcknowledgements\nNo funding was utilized for support of this case report.\n==== Refs\nReferences\n1. Moawad NS Mahajan ST Moniz MH Taylor SE Hurd WW Current diagnosis and treatment of interstitial pregnancy Am J Obstet Gynecol 2010 202 1 15 29 10.1016/j.ajog.2009.07.054 20096253 \n2. Tulandi T Monton L Conservative surgical management of interstitial pregnancy Fertil Steril 1990 53 3 581 2407570 \n3. Tulandi T Al-Jaroudi D Interstitial pregnancy: results generated from the Society of Reproductive Surgeons Registry Obstet Gynecol 2004 103 1 47 50 10.1097/01.AOG.0000109218.24211.79 14704243 \n4. Fabre-Gray A Read M Wardle P James M Recurrent cornual pregnancy, successfully treated with methotrexate, following a ruptured pregnancy in the contralateral cornu J Obstet Gynaecol 2014 34 1 85 10.3109/01443615.2013.819844 24359059 \n5. Timor-Tritsch IE Monteagudo A Matera C Veit CR Sonographic evolution of cornual pregnancies treated without surgery Obstet Gynecol 1992 79 6 1044 9 1579304 \n6. Swank ML Harken TR Porto M Management of interstitial ectopic pregnancies with a combined intra-amniotic and systemic approach Obstet Gynecol 2013 122 2 Pt 2 461 4 10.1097/AOG.0b013e31828d58ee 23884260 \n7. Goldthwaite LM Edwards L Tocce K Early hysteroscopic removal of intratubal microinserts with urologic stone retrieval forceps Obstet Gynecol 2014 124 2 Pt 2 Suppl 1 441 4 10.1097/AOG.0000000000000338 25004312 \n8. Buster JE Heard MJ Current issues in medical management of ectopic pregnancy Curr Opin Obstet Gynecol 2000 12 6 525 7 10.1097/00001703-200012000-00012 11128417 \n9. Hiersch L Krissi H Ashwal E From A Wiznitzer A Peled Y Effectiveness of medical treatment with methotrexate for interstitial pregnancy Aust N Z J Obstet Gynaecol 2014 54 6 576 80 10.1111/ajo.12251 25338827 \n10. Warda H Mamik MM Ashraf M Abuzeid MI Interstitial ectopic pregnancy: conservative surgical management JSLS 2014 18 2 197 203 10.4293/108680813X13753907292836 24960482 \n11. Nezhat CH Dun EC Laparoscopically-assisted, hysteroscopic removal of an interstitial pregnancy with a fertility-preserving technique J Minim Invasive Gynecol 2014 21 6 1091 4 10.1016/j.jmig.2014.04.007 24768982 \n12. Cai Z Wang F Cao H Xia Q Chen X Cai Y The value of laparoscopy alone or combined with hysteroscopy in the treatment of interstitial pregnancy: analysis of 22 cases Arch Gynecol Obstet 2012 285 3 727 32 10.1007/s00404-011-2060-1 21874409 \n13. Ahn JW Lee SJ Lee SH Kang SP Won HS Ultrasound-guided transcervical forceps extraction of unruptured interstitial pregnancy BJOG 2013 120 10 1285 8 10.1111/1471-0528.12265 23683343 \n14. Fritz RB Rosenblum N Gaither K Sherman A McCalla A Successful laparoscopically assisted transcervical suction evacuation of interstitial pregnancy following failed methotrexate injection in a community hospital setting Case Rep Obstetr Gynecol. 2014 2014 695293 \n15. Minelli L Landi S Trivella G Fiaccavento A Barbieri F Cornual pregnancy successfully treated by suction curettage and operative hysteroscopy BJOG 2003 110 12 1132 4 10.1111/j.1471-0528.2003.03088.x 14664889 \n16. Radwan Faraj MS Review: management of cornual (interstitial) pregnancy Obstetr Gynaecol. 2007 9 249 55 10.1576/toag.9.4.249.27355 \n17. Khawaja N Walsh T Gill B Uterine artery ligation for the management of ruptured cornual ectopic pregnancy Eur J Obstet Gynecol Reprod Biol 2005 118 2 269 10.1016/j.ejogrb.2004.05.006 15653221 \n18. Tulandi T Vilos G Gomel V Laparoscopic treatment of interstitial pregnancy Obstet Gynecol 1995 85 3 465 7 10.1016/0029-7844(94)00423-B 7862394 \n19. Moon HS Choi YJ Park YH Kim SG New simple endoscopic operations for interstitial pregnancies Am J Obstet Gynecol 2000 182 1 Pt 1 114 21 10.1016/S0002-9378(00)70499-6 10649165 \n20. Shendy M, Atalla R. Modern management of cornual ectopic pregnancy. In: Kamrava M, editor. Ectopic pregnancy – modern diagnosis and management. Croatia: InTech; 2011. p. 238–48.\n21. Budnick SG Jacobs SL Nulsen JC Metzger DA Conservative management of interstitial pregnancy Obstet Gynecol Surv 1993 48 10 694 8 10.1097/00006254-199310000-00025 8247463 \n22. Weissman A Fishman A Uterine rupture following conservative surgery for interstitial pregnancy Eur J Obstet Gynecol Reprod Biol 1992 44 3 237 9 10.1016/0028-2243(92)90105-8 1607064\n\n", "fulltext_license": "CC BY", "issn_linking": "1752-1947", "issue": "10(1)", "journal": "Journal of medical case reports", "keywords": "Cornual pregnancy; Ectopic pregnancy; Interstitial pregnancy; Minimally invasive surgery; Persistent products of conception", "medline_ta": "J Med Case Rep", "mesh_terms": "D000020:Abortifacient Agents, Nonsteroidal; D000027:Abortion, Incomplete; D000328:Adult; D004107:Dilatation and Curettage; D005260:Female; D006801:Humans; D015907:Hysteroscopy; D010535:Laparoscopy; D008727:Methotrexate; D011247:Pregnancy; D065173:Pregnancy, Cornual", "nlm_unique_id": "101293382", "other_id": null, "pages": "106", "pmc": null, "pmid": "27118381", "pubdate": "2016-04-27", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "2407570;8247463;15653221;23884260;1579304;21874409;11128417;10649165;25004312;23683343;24649387;25338827;20096253;24768982;1607064;24359059;24960482;14704243;7862394;14664889", "title": "Considerations for management of interstitial ectopic pregnancies: two case reports.", "title_normalized": "considerations for management of interstitial ectopic pregnancies two case reports" }

[ { "companynumb": "US-ANTARES PHARMA, INC.-2016-LIT-ME-0280", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "204824", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ECTOPIC PREGNANCY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." } ], "patientagegroup": null, "patientonsetage": "33", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "19.1", "reactionoutcome": null } ], "summary": null }, "primarysource": { "literaturereference": "GRINDLER ET AL.. CONSIDERATIONS FOR MANAGEMENT OF INTERSTITIAL ECTOPIC PREGNANCIES: TWO CASE REPORTS.. JOURNAL OF MEDICAL CASE REPORTS. 2016 JAN 01;.", "literaturereference_normalized": "considerations for management of interstitial ectopic pregnancies two case reports", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20160804", "receivedate": "20160804", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12621871, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20161109" } ]

{ "abstract": "Two female patients aged 70 and 72 with video-urodynamics-confirmed detrusor overactivity and detrusor underactivity (DO-DU) were treated. Patients were refractory to medical therapies and had previously failed intravesical botulinum toxin type A (BoNT-A) at other centers secondary to urinary retention and difficulty with self-catheterization. Placement of an Interstim II device (Medtronic, Minneapolis, Minnesota) for sacral neuromodulation (SNM) as alternative third-line treatment partially improved overactive bladder (OAB) symptoms while significantly improving voiding symptoms. Postvoid residual (PVR) of patients improved from a median of 118 mL (110-125 mL) to 20 mL (18-26 mL) and 213 mL (195-230 mL) to 70 mL (60-73 mL), respectively. Addition of medical therapies post SNM failed to modify OAB symptoms further and a rechallenge with dose-reduced BoNT-A was undertaken.OAB symptoms were significantly improved by addition of BoNT-A, while urinary retention was avoided (median PVR post BoNT-A 38 mL [34-40 mL] and 185 mL [150-205 mL], respectively). Reduction in incontinence pad use as well as resolution of nighttime incontinence in both patients and daytime incontinence in one patient was achieved. DO-DU patients treated by SNM who have improved bladder emptying (PVR <100 mL) but incomplete resolution of OAB symptoms should be trialed on adjunct medical therapies to improve OAB symptoms. If OAB symptoms are still inadequately controlled, consideration of a rechallenge with BoNT-A, particularly with dose reduction, appears to be efficacious and avoids symptomatic retention in this challenging cohort.", "affiliations": "Department of Urology, Austin Health, Heidelberg, Victoria, Australia.;Department of Urology, Austin Health, Heidelberg, Victoria, Australia.;Department of Urology, Austin Health, Heidelberg, Victoria, Australia.;Department of Urology, Austin Health, Heidelberg, Victoria, Australia.", "authors": "Timm|Brennan|B|https://orcid.org/0000-0001-6195-3364;Jayarajan|Jyotsna|J|;Chan|Garson|G|https://orcid.org/0000-0002-2241-6635;Bolton|Damien|D|", "chemical_list": "D019274:Botulinum Toxins, Type A", "country": "Australia", "delete": false, "doi": "10.1111/luts.12332", "fulltext": null, "fulltext_license": null, "issn_linking": "1757-5664", "issue": "13(1)", "journal": "Lower urinary tract symptoms", "keywords": "BoNT-A; Botox; DO-DU; OAB; UUI; acute urinary retention; overactive bladder", "medline_ta": "Low Urin Tract Symptoms", "mesh_terms": "D000368:Aged; D019274:Botulinum Toxins, Type A; D005260:Female; D006801:Humans; D012447:Sacrum; D004561:Transcutaneous Electric Nerve Stimulation; D053201:Urinary Bladder, Overactive; D053202:Urinary Incontinence, Urge; D016055:Urinary Retention", "nlm_unique_id": "101506777", "other_id": null, "pages": "194-197", "pmc": null, "pmid": "32548938", "pubdate": "2021-01", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Botox rechallenge-An additional tool in the management of an incompletely emptying bladder and inadequate overactive symptom control following sacral neuromodulation.", "title_normalized": "botox rechallenge an additional tool in the management of an incompletely emptying bladder and inadequate overactive symptom control following sacral neuromodulation" }

[ { "companynumb": "AU-IPSEN BIOPHARMACEUTICALS, INC.-2020-12035", "fulfillexpeditecriteria": "1", "occurcountry": "AU", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BOTULINUM TOXIN TYPE A" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "OFF LABEL USE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BOTULINUM TOXIN TYPE A" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "BOTULINUM TOXIN TYPE A" }, "drugadditional": null, "drugadministrationroute": "043", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "POWDER FOR SOLUTION FOR INJECTION", "drugdosagetext": "INITIALLY WITH 100 UNITS AND SUBSEQUENTLY WITH DOSE REDUCTION TO 55 UNITS.", "drugenddate": null, "drugenddateformat": null, "drugindication": "URINARY INCONTINENCE", "drugintervaldosagedefinition": "811", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "025", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BOTULINUM TOXIN TYPE A" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Urinary retention", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug effective for unapproved indication", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "TIMM B, JAYARAJAN J, CHAN G, BOLTON D. BOTOX RECHALLENGE?AN ADDITIONAL TOOL IN THE MANAGEMENT OF AN INCOMPLETELY EMPTYING BLADDER AND INADEQUATE OVERACTIVE SYMPTOM CONTROL FOLLOWING SACRAL NEUROMODULATION. LOWER URINARY TRACT SYMPTOMS. 2020?1?4. DOI:HTTPS://DOI.ORG/10.1111/LUTS.12332", "literaturereference_normalized": "botox rechallenge an additional tool in the management of an incompletely emptying bladder and inadequate overactive symptom control following sacral neuromodulation", "qualification": "3", "reportercountry": "AU" }, "primarysourcecountry": "AU", "receiptdate": "20200715", "receivedate": "20200713", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18018040, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" } ]

{ "abstract": "OBJECTIVE\nPregabalin is a novel GABA-analogue approved for the treatment of partial onset seizures, neuropathic pain, and general anxiety disorder. Pregabalin has been classified as a Schedule V drug with a low risk of inflicting abuse or addiction. However, some publications have indicated that pregabalin may have a potential for abuse among patients with past or current opiate addiction. Thus, we hypothesized that pregabalin might be abused by patients who were undergoing an opiate replacement therapy and never had an indication for taking pregabalin on medical grounds.\n\n\nMETHODS\nUrine specimens from 124 patients with opiate dependency syndrome and from 111 patients with other addiction disorders (alcohol, benzodiazepines, cannabis, amphetamines) were screened for pregabalin by means of a mass spectrometer analysis.\n\n\nRESULTS\nWe found 12.1 % of all urine specimens from patients with opiate addiction to be positive for pregabalin. None of the patients concerned had a medical indication for using pregabalin. In the control group, 2.7 % of the patients were tested positively for pregabalin, due to their taking it regularly for chronic pain or general anxiety.\n\n\nCONCLUSIONS\nOur data suggest that pregabalin is liable to be abused among individuals with opiate dependency syndrome Thus, vigilance and caution are called for when patients with a past or current opiate dependency are exposed to treatment with pregabalin.", "affiliations": "Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, J5/68159, Mannheim, Germany, martin.grosshans@zi-mannheim.de.", "authors": "Grosshans|Martin|M|;Lemenager|Tagrid|T|;Vollmert|Christian|C|;Kaemmerer|Nina|N|;Schreiner|Rupert|R|;Mutschler|Jochen|J|;Wagner|Xenija|X|;Kiefer|Falk|F|;Hermann|Derik|D|", "chemical_list": "D000700:Analgesics; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid", "country": "Germany", "delete": false, "doi": "10.1007/s00228-013-1578-5", "fulltext": null, "fulltext_license": null, "issn_linking": "0031-6970", "issue": "69(12)", "journal": "European journal of clinical pharmacology", "keywords": null, "medline_ta": "Eur J Clin Pharmacol", "mesh_terms": "D000328:Adult; D000700:Analgesics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D000069583:Pregabalin; D019966:Substance-Related Disorders; D055815:Young Adult; D005680:gamma-Aminobutyric Acid", "nlm_unique_id": "1256165", "other_id": null, "pages": "2021-5", "pmc": null, "pmid": "23989299", "pubdate": "2013-12", "publication_types": "D016428:Journal Article", "references": "20595436;21740692;20078487;20147618;20972557;19588419;17610384;21197312;16172090;21334859;21068226;20373479;20563568;22689280;17379045;15303247;12452551;16503325;20531222;21423307;16050051;19346279;15315512;22085697", "title": "Pregabalin abuse among opiate addicted patients.", "title_normalized": "pregabalin abuse among opiate addicted patients" }

[ { "companynumb": "DE-PFIZER INC-2015045644", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M.. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771594, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045641", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M.. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771577, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045636", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M.. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771547, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045643", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M.. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771576, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045640", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771536, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045649", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS, M.. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771532, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045645", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M.. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771592, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045638", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS, M.. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771580, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045642", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771590, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045639", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771535, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045610", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10770685, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045646", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS, M.. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771595, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045637", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771551, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045648", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M.. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771531, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "DE-PFIZER INC-2015045647", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "021446", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug abuse", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GROSSHANS M. PREGABALIN ABUSE AMONG OPIATE ADDICTED PATIENTS. EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. 2013;69 (12):2021-2025", "literaturereference_normalized": "pregabalin abuse among opiate addicted patients", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20150206", "receivedate": "20150206", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10771533, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" } ]

{ "abstract": "Bacillary angiomatosis (BA) is a disorder of neovascular proliferation involving skin and other organs of immunosuppressed patients caused by Bartonella species. BA has been recognized in both immunocompetent and immunodeficient patients, mostly in human immunodeficiency virus (HIV)-infected persons, much more rare in those with other immunodeficiencies, including organ transplantation. Diagnosis is based on serologic analysis, culture and molecular biology [detection of Bartonella species deoxyribonucleic acid (DNA) in tissue biopsy extracts by real-time polymerase chain reaction (PCR)]. All immunosuppressed patients with BA should be treated with antibiotics because of potentially life-threatening course of the disease. We report the first case of cutaneous bacillary angiomatosis due to Bartonella quintana in renal transplant recipient. This presentation demonstrates that BA should be considered a differential diagnosis in immunocompromised patients presenting with fever and cutaneous angioma-like lesions.", "affiliations": "Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czech Republic.", "authors": "Orsag|Jiri|J|;Flodr|Patrik|P|;Melter|Oto|O|;Tkadlec|Jan|J|;Sternbersky|Jan|J|;Hruby|Miroslav|M|;Klicova|Anna|A|;Zamboch|Kamil|K|;Krejci|Karel|K|;Zadrazil|Josef|J|", "chemical_list": "D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D004247:DNA", "country": "England", "delete": false, "doi": "10.1111/tri.12539", "fulltext": null, "fulltext_license": null, "issn_linking": "0934-0874", "issue": "28(5)", "journal": "Transplant international : official journal of the European Society for Organ Transplantation", "keywords": "Bartonella quintana; bacillary angiomatosis; immunosuppression; renal transplantation", "medline_ta": "Transpl Int", "mesh_terms": "D000293:Adolescent; D000328:Adult; D016917:Angiomatosis, Bacillary; D000900:Anti-Bacterial Agents; D018413:Bartonella quintana; D001706:Biopsy; D002648:Child; D004247:DNA; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents; D007676:Kidney Failure, Chronic; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult", "nlm_unique_id": "8908516", "other_id": null, "pages": "626-31", "pmc": null, "pmid": "25652715", "pubdate": "2015-05", "publication_types": "D002363:Case Reports; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't", "references": null, "title": "Cutaneous bacillary angiomatosis due to Bartonella quintana in a renal transplant recipient.", "title_normalized": "cutaneous bacillary angiomatosis due to bartonella quintana in a renal transplant recipient" }

[ { "companynumb": "CZ-ALKEM LABORATORIES LIMITED-CZ-ALKEM-2020-01783", "fulfillexpeditecriteria": "1", "occurcountry": "CZ", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "CYCLOSPORINE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOSPORIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "091249", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Bacillary angiomatosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Haemophagocytic lymphohistiocytosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "ORSAG J, FLODR P, MELTER O, TKADLEC J ET AL. CUTANEOUS BACILLARY ANGIOMATOSIS DUE TO BARTONELLA QUINTANA IN A RENAL TRANSPLANT RECIPIENT. TRANSPLANT INTERNATIONAL. 2015?28:626-631", "literaturereference_normalized": "cutaneous bacillary angiomatosis due to bartonella quintana in a renal transplant recipient", "qualification": "1", "reportercountry": "CZ" }, "primarysourcecountry": "CZ", "receiptdate": "20200514", "receivedate": "20200514", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17780187, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "US-ALKEM LABORATORIES LIMITED-US-ALKEM-2020-01790", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CYCLOSPORINE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "125 MILLIGRAM, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "12", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "125", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOSPORINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "091249", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "500 MILLIGRAM, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "12", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." } ], "patientagegroup": null, "patientonsetage": "8", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Post transplant lymphoproliferative disorder", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bacillary angiomatosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cat scratch disease", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "ORSAG J, FLODR P, MELTER O, TKADLEC J, ET.AL. CUTANEOUS BACILLARY ANGIOMATOSIS DUE TO BARTONELLA QUINTANA IN A RENAL TRANSPLANT RECIPIENT. TRANSPLANT INTERNATIONAL. 2015?UNK:626?631", "literaturereference_normalized": "cutaneous bacillary angiomatosis due to bartonella quintana in a renal transplant recipient", "qualification": "3", "reportercountry": "CZ" }, "primarysourcecountry": "US", "receiptdate": "20201229", "receivedate": "20201229", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18673077, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20210114" } ]

{ "abstract": "Stiff person syndrome is a neuroimmunological disorder characterized by progressive muscular rigidity and spasms that affect axial/limb muscles, resulting in severe pain and functional limitations. When refractory to conservative treatments, intrathecal baclofen is a viable option to treat the increased tone. Intrathecal baclofen has been shown to accelerate underlying neuromuscular scoliosis in the pediatric population with cerebral palsy. This adverse effect has never been reported in adults with stiff person syndrome. We report a case of an adult with stiff person syndrome and underlying scoliosis who experienced accelerated progression of scoliosis after initiation of intrathecal baclofen, subsequently requiring neurosurgical intervention.", "affiliations": "From the Department of Rehabilitation and Regenerative Medicine, NewYork-Presbyterian Hospital-University Hospital of Columbia and Cornell, New York, New York.;From the Department of Rehabilitation and Regenerative Medicine, NewYork-Presbyterian Hospital-University Hospital of Columbia and Cornell, New York, New York.;Weill Cornell Medical College, New York, New York.;Department of Physical Medicine & Rehabilitation, Center for Comprehensive Spine Care, Weill Cornell Medicine, New York, New York.", "authors": "Oh|Daniel Chun-Suk|DC|;Rakesh|Neal|N|;LaGrant|Brian|B|;Sein|Michael|M|", "chemical_list": "D001418:Baclofen", "country": "United States", "delete": false, "doi": "10.1213/XAA.0000000000001204", "fulltext": null, "fulltext_license": null, "issn_linking": "2575-3126", "issue": "14(6)", "journal": "A&A practice", "keywords": null, "medline_ta": "A A Pract", "mesh_terms": "D000328:Adult; D001418:Baclofen; D002648:Child; D006801:Humans; D012600:Scoliosis; D016750:Stiff-Person Syndrome", "nlm_unique_id": "101714112", "other_id": null, "pages": "e01204", "pmc": null, "pmid": "32759618", "pubdate": "2020-04", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Advanced Progression of Scoliosis After Intrathecal Baclofen in an Adult With Stiff Person Syndrome: A Case Report.", "title_normalized": "advanced progression of scoliosis after intrathecal baclofen in an adult with stiff person syndrome a case report" }

[ { "companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2020R1-271873", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "3", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": "77862", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "475.1 MICROGRAM, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "475.1", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "3", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": null, "drugadministrationroute": "037", "drugauthorizationnumb": "77862", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MICROGRAM, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "MUSCLE SPASMS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "3", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "77862", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM,EVERY 6 HOURS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." } ], "patientagegroup": null, "patientonsetage": "59", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Disease progression", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "OH DCS, RAKESH N, LAGRANT B, SEIN M. ADVANCED PROGRESSION OF SCOLIOSIS AFTER INTRATHECAL BACLOFEN IN AN ADULT WITH STIFF PERSON SYNDROME A CASE REPORT. A A PRACT. 2020?14(6):E01204", "literaturereference_normalized": "advanced progression of scoliosis after intrathecal baclofen in an adult with stiff person syndrome a case report", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201221", "receivedate": "20201221", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18643526, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" }, { "companynumb": "US-DRREDDYS-USA/USA/20/0130151", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "DIAZEPAM" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "6", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIAZEPAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TIZANIDINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "076286", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "6", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TIZANIDINE HYDROCHLORIDE." }, { "actiondrug": null, "activesubstance": null, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMMUNOGLOBULIN" } ], "patientagegroup": "6", "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "OH D, RAKESH N, LAGRANT B, SEIN M. ADVANCED PROGRESSION OF SCOLIOSIS AFTER INTRATHECAL BACLOFEN IN AN ADULT WITH STIFF PERSON SYNDROME: A CASE REPORT. A AND A PRACTICE. 2020 JAN?14(6):E01204-E01204. DOI:10.1213/XAA.0000000000001204", "literaturereference_normalized": "advanced progression of scoliosis after intrathecal baclofen in an adult with stiff person syndrome a case report", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201216", "receivedate": "20201216", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18621866, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" }, { "companynumb": "US-OXFORD PHARMACEUTICALS, LLC-2020OXF00070", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "DIAZEPAM" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MG, EVERY 6 HOURS AS NEEDED", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "4", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIAZEPAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TIZANIDINE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "6 MG, EVERY 8 HOURS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "3", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "6", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TIZANIDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "3", "drugadministrationroute": "037", "drugauthorizationnumb": "077088", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "100 ?G PER DAY VIA IMPLANTED PUMP, TITRATED TO 475.1 ?G OVER 5 YEARS", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG, EVERY 6 HOURS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "4", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." } ], "patientagegroup": null, "patientonsetage": "59", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Scoliosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "OH DC-S, RAKESH N, LAGRANT B, SEIN M. ADVANCED PROGRESSION OF SCOLIOSIS AFTER INTRATHECAL BACLOFEN IN AN ADULT WITH STIFF PERSON SYNDROME: A CASE REPORT. A A PRACT. 2020", "literaturereference_normalized": "advanced progression of scoliosis after intrathecal baclofen in an adult with stiff person syndrome a case report", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200608", "receivedate": "20200608", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17871009, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "US-AMNEAL PHARMACEUTICALS-2020-AMRX-01545", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "3", "drugadministrationroute": "037", "drugauthorizationnumb": "077971", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." } ], "patientagegroup": null, "patientonsetage": "59", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Scoliosis", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Condition aggravated", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "OH D.CS, RAKESH N, LAGRANT B, SEIN M. ADVANCED PROGRESSION OF SCOLIOSIS AFTER INTRATHECAL BACLOFEN IN AN ADULT WITH STIFF PERSON SYNDROME: A CASE REPORT. PM R. 2019?11:2 (S23)", "literaturereference_normalized": "advanced progression of scoliosis after intrathecal baclofen in an adult with stiff person syndrome a case report", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200609", "receivedate": "20200601", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17846529, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "US-MYLANLABS-2020M1103265", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "077121", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "10 MILLIGRAM, Q6H", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "6", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "3", "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "475.1 MICROGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "475.1", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "GABAPENTIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NEURALGIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GABAPENTIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NEURALGIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." }, { "actiondrug": "5", "activesubstance": null, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMMUNE GLOBULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "3", "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "100 MICROGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "TIZANIDINE" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "6 MILLIGRAM, Q8H", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "6", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TIZANIDINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DIAZEPAM" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "5 MILLIGRAM, Q6H", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "6", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIAZEPAM." } ], "patientagegroup": null, "patientonsetage": "6", "patientonsetageunit": "800", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Epistaxis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Disease progression", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Scoliosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "OH DC-S, RAKESH N, LAGRANT B, SEIN M. ADVANCED PROGRESSION OF SCOLIOSIS AFTER INTRATHECAL BACLOFEN IN AN ADULT WITH STIFF PERSON SYNDROME: A CASE REPORT. A-A-PRACT 2020?14(6):E01204.", "literaturereference_normalized": "advanced progression of scoliosis after intrathecal baclofen in an adult with stiff person syndrome a case report", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201217", "receivedate": "20201217", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18629772, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" }, { "companynumb": "US-CADILA HEALTHCARE LIMITED-US-ZYDUS-059471", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "3", "drugadministrationroute": "037", "drugauthorizationnumb": "211659", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "475.1 MICROGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "475.1", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIAZEPAM" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MILLIGRAM, QID", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIAZEPAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TIZANIDINE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "6 MILLIGRAM, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "6", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TIZANIDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "211659", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MILLIGRAM, QID", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "3", "drugadministrationroute": "037", "drugauthorizationnumb": "211659", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MICROGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Epistaxis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Disease progression", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Scoliosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "OH DC-S, RAKESH N, LAGRANT B, SEIN M.. ADVANCED PROGRESSION OF SCOLIOSIS AFTER INTRATHECAL BACLOFEN IN AN ADULT WITH STIFF PERSON SYNDROME: A CASE REPORT. A + A PRACTICE. 2020?14(6):E01204", "literaturereference_normalized": "advanced progression of scoliosis after intrathecal baclofen in an adult with stiff person syndrome a case report", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201228", "receivedate": "20201228", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18668145, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" }, { "companynumb": "US-TEVA-2020-US-1860964", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "TIZANIDINE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "18 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "6", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TIZANIDINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "3", "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MICROGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IMMUNE GLOBULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IMMUNE GLOBULIN (IMMUNOGLOBULINS NOS)" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREGABALIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NEURALGIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREGABALIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "72234", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "6", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "BACLOFEN" }, "drugadditional": "3", "drugadministrationroute": "037", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "475.1 MICROGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "475.1", "drugstructuredosageunit": "004", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BACLOFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "GABAPENTIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NEURALGIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GABAPENTIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "085600", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIAZEPAM" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "70152", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "6", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIAZEPAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "080356", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "STIFF PERSON SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." } ], "patientagegroup": "5", "patientonsetage": "6", "patientonsetageunit": "800", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Epistaxis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fatigue", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Scoliosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Headache", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "OH DC?S, RAKESH N, LAGRANT B, SEIN M. ADVANCED PROGRESSION OF SCOLIOSIS AFTER INTRATHECAL BACLOFEN IN AN ADULT WITH STIFF PERSON SYNDROME: A CASE REPORT. A?A?PRACT 2020?14(6):E01204.", "literaturereference_normalized": "advanced progression of scoliosis after intrathecal baclofen in an adult with stiff person syndrome a case report", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210126", "receivedate": "20201223", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18658591, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210419" } ]

{ "abstract": "BACKGROUND\nThe purpose of this study was to evaluate the clinical impact of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in terms of the response rate, progression-free/overall survival (PFS/OS) and safety profile in patients with heavily pretreated recurrent epithelial ovarian cancer.\n\n\nMETHODS\nClinical data were reviewed in 29 patients who received FOLFOX-4 as more than third-line chemotherapy, consisting of 85 mg/m2 of oxaliplatin, 200 mg/m2 of leucovorin, and bolus 400 mg/m2 on day 1 of 5-fluorouracil, followed by a 22-h infusion of 600 mg/m2 of 5-fluorouracil for 2 consecutive days every 3 weeks. We also compared the efficacy and toxicity of FOLFOX-4 with that of topotecan, a standard treatment, given at a dosage of 1.5 mg/m2 every three weeks in 26 patients.\n\n\nRESULTS\nThe median age of enrolled patients was 60 years (range 33 to 85). A median of 4 cycles (range 1-17) of FOLFOX-4 were administered. Complete response and partial response were observed in one (3.5%) and 5 (17.2.2%) patients, respectively, while stable disease was reported in 8 (27.6%) patients. Among all patients, grade 3-4 anemia, neutropenia, and thrombocytopenia were observed in 0 (0%), 5 (17.2%), and 3 (10.3%) cases, respectively. Grade 3-4 fatigue was recorded in one (3.4%) patient and diarrhea in 2 (6.9%). Median PFS and OS were 2.8 months [95% confidence interval (CI) 1.7-4.9] and 6.2 months (95% CI 2.4-14.6), respectively. No significant differences in terms of efficacy and toxicity were observed between patients receiving FOLFOX-4 and those treated with topotecan.\n\n\nCONCLUSIONS\nThe FOLFOX-4 regimen would seem to obtain similar survival rates to those of standard therapy with topotecan in platinum-resistant ovarian cancer. Further randomized trials are warranted to confirm our findings.", "affiliations": "Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy. cinzia.conteduca@libero.it.;Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.;Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.;Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.;Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.;Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.;Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.;Medical Oncology Department, Campus Bio-Medico University, Via Alvaro del Portillo 200, 00128, Rome, Italy.;Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.;Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.;Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.;Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Morgagni-Pierantoni Hospital, Forlì, Italy.;Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, 41125, Modena, Italy.;Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.;Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, 41125, Modena, Italy.;Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014, Meldola, FC, Italy.", "authors": "Conteduca|Vincenza|V|http://orcid.org/0000-0002-6921-714X;Gurioli|Giorgia|G|;Rossi|Lorena|L|;Scarpi|Emanuela|E|;Lolli|Cristian|C|;Schepisi|Giuseppe|G|;Farolfi|Alberto|A|;De Lisi|Delia|D|;Gallà|Valentina|V|;Burgio|Salvatore Luca|SL|;Menna|Cecilia|C|;Amadori|Andrea|A|;Losi|Lorena|L|;Amadori|Dino|D|;Costi|Maria Paola|MP|;De Giorgi|Ugo|U|", "chemical_list": "D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil", "country": "England", "delete": false, "doi": "10.1186/s12885-018-5180-1", "fulltext": "\n==== Front\nBMC CancerBMC CancerBMC Cancer1471-2407BioMed Central London 518010.1186/s12885-018-5180-1Research ArticleOxaliplatin plus leucovorin and 5-fluorouracil (FOLFOX-4) as a salvage chemotherapy in heavily-pretreated platinum-resistant ovarian cancer http://orcid.org/0000-0002-6921-714XConteduca Vincenza +39-0543-739100cinzia.conteduca@libero.it 1Gurioli Giorgia giorgia.gurioli@irst.emr.it 2Rossi Lorena lorena.rossi@irst.emr.it 1Scarpi Emanuela emanuela.scarpi@irst.emr.it 3Lolli Cristian cristian.lolli@irst.emr.it 1Schepisi Giuseppe giuseppe.schepisi@irst.emr.it 1Farolfi Alberto alberto.farolfi@irst.emr.it 1De Lisi Delia delisidelia@gmail.com 4Gallà Valentina valentina.galla@irst.emr.it 1Burgio Salvatore Luca salvatore.burgio@irst.emr.it 1Menna Cecilia cecilia.menna@irst.emr.it 1Amadori Andrea dott.amadori@gmail.com 5Losi Lorena lorena.losi@unimore.it 6Amadori Dino dino.amadori@irst.emr.it 1Costi Maria Paola mariapaola.costi@unimore.it 6De Giorgi Ugo ugo.degiorgi@irst.emr.it 11 0000 0004 1755 9177grid.419563.cMedical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Via Piero Maroncelli 40, 47014 Meldola, FC Italy 2 0000 0004 1755 9177grid.419563.cBiosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 3 0000 0004 1755 9177grid.419563.cUnit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 4 0000 0004 1757 5329grid.9657.dMedical Oncology Department, Campus Bio-Medico University, Via Alvaro del Portillo 200, 00128 Rome, Italy 5 0000 0004 1759 989Xgrid.415079.eDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, Morgagni-Pierantoni Hospital, Forlì, Italy 6 0000000121697570grid.7548.eDepartment of Life Sciences, University of Modena and Reggio Emilia, Via Campi 183, 41125 Modena, Italy 19 12 2018 19 12 2018 2018 18 126714 9 2018 4 12 2018 © The Author(s). 2018Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background\nThe purpose of this study was to evaluate the clinical impact of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in terms of the response rate, progression-free/overall survival (PFS/OS) and safety profile in patients with heavily pretreated recurrent epithelial ovarian cancer.\n\nMethods\nClinical data were reviewed in 29 patients who received FOLFOX-4 as more than third-line chemotherapy, consisting of 85 mg/m2 of oxaliplatin, 200 mg/m2 of leucovorin, and bolus 400 mg/m2 on day 1 of 5-fluorouracil, followed by a 22-h infusion of 600 mg/m2 of 5-fluorouracil for 2 consecutive days every 3 weeks. We also compared the efficacy and toxicity of FOLFOX-4 with that of topotecan, a standard treatment, given at a dosage of 1.5 mg/m2 every three weeks in 26 patients.\n\nResults\nThe median age of enrolled patients was 60 years (range 33 to 85). A median of 4 cycles (range 1–17) of FOLFOX-4 were administered. Complete response and partial response were observed in one (3.5%) and 5 (17.2.2%) patients, respectively, while stable disease was reported in 8 (27.6%) patients. Among all patients, grade 3–4 anemia, neutropenia, and thrombocytopenia were observed in 0 (0%), 5 (17.2%), and 3 (10.3%) cases, respectively. Grade 3–4 fatigue was recorded in one (3.4%) patient and diarrhea in 2 (6.9%). Median PFS and OS were 2.8 months [95% confidence interval (CI) 1.7–4.9] and 6.2 months (95% CI 2.4–14.6), respectively. No significant differences in terms of efficacy and toxicity were observed between patients receiving FOLFOX-4 and those treated with topotecan.\n\nConclusions\nThe FOLFOX-4 regimen would seem to obtain similar survival rates to those of standard therapy with topotecan in platinum-resistant ovarian cancer. Further randomized trials are warranted to confirm our findings.\n\nKeywords\nFOLFOX-4FluorouracilTopotecanOvarian cancerPlatinum resistanceSurvivalissue-copyright-statement© The Author(s) 2018\n==== Body\nBackground\nOvarian cancer remains a highly lethal malignancy, representing the sixth leading cause of cancer death in women and the most lethal gynecologic malignancy [1, 2]. The prognosis for advanced ovarian cancer has improved over the last 10 years, especially thanks mainly to the introduction of more personalized therapeutic strategies. However, despite the high response rate to the standard carboplatin-paclitaxel first-line combination, most patients develop recurrent disease, with a median survival ranging from 12 to 24 months. Patients who progress on cisplatin or carboplatin or who relapse within 6 months of the end of treatment show the poorest outcome [2]. Single-agent therapies for platinum-refractory/resistant patients include oral etoposide, taxanes, topotecan, gemcitabine, vinorelbine, liposomal doxorubicin, and oxaliplatin, with response rates of around 15–20% and an overall survival (OS) of less than 12 months [3]. Research is now aiming to improve chemotherapy, identify novel, effective and well-tolerated agents, and overcome platinum resistance.\n\nCisplatin and carboplatin are the most common platinum compounds used to treat ovarian cancer. Oxaliplatin, a diaminocyclohexane platinum compound, has a different spectrum of activity and toxicity to that of other platinum agents and does not usually show cross-resistance with cisplatin and carboplatin in ovarian cancer [4, 5]. In previous phase II studies, oxaliplatin at a dose of 130 mg/m2 every 3 weeks was administered to patients with cisplatin- or carboplatin-refractory/resistant and taxane-pretreated ovarian cancer, obtaining response rates of 4.3–29.0% and a median OS of 9.5–15 months [6–9]. The combination of 5-fluorouracil with leucovorin given as intravenous bolus or continuous infusion has also been used to treat platinum-resistant/recurrent ovarian cancer but has shown limited clinical activity [10–14].\n\nSome in vitro studies indicate a potential synergy between oxaliplatin and 5-fluorouracil/leucovorin [15]. The combination of these drugs (called FOLFOX) represents a standard chemotherapeutic regimen in the management of some advanced tumours [16–18]. Preliminary data on the use of this treatment in recurrent ovarian cancer have not been entirely satisfactory/have not been encouraging [19–22]. In the present study we evaluated the efficacy, in terms of clinical outcome, and toxicity of FOLFOX-4 in platinum-resistant ovarian cancer. In addition, through an exploratory analysis, we compared our results with data from patients treated with topotecan, a drug usually administered alone as salvage chemotherapy in platinum-resistant disease.\n\nMethods\nStudy population\nWe retrospectively evaluated 29 patients treated with the FOLFOX-4 regimen from February 2008 to April 2016 as the primary cohort, and 26 patients treated with topotecan between August 2010 and December 2014 as the secondary cohort. Eligibility criteria of both cohorts were histological confirmation of epithelial ovarian cancer, previous treatment with cisplatin or carboplatin plus paclitaxel regimens, and disease recurrence during treatment with or within 6 months of the end of the cisplatin or carboplatin-based chemotherapy. Additional eligibility criteria included Eastern Cooperative Oncology Group (ECOG) performance status 0–2, and adequate cardiac, renal, hepatic and bone marrow function. Metastatic disease was documented by bone scan, computed tomography or magnetic resonance imaging. The retrospective study was approved by the Institutional Review Board of Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS and was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. The need for written informed consent from participants was waived because of the retrospective nature of the research.\n\nPatients were evaluated for safety and dosing compliance every 2 weeks for the first 3 months of chemotherapy, and then monthly thereafter until treatment discontinuation. Renal, liver and bone marrow function were assessed at every cycle, while cancer antigen 125 (CA-125) and radiographic evaluation were left to the discretion of the treating physician, but were usually performed after at least three months’ treatment.\n\nTreatment and evaluation\nTreatment with FOLFOX-4 consisted of 85 mg/m2 of oxaliplatin as a 2-h infusion on day 1, 200 mg/m2 of leucovorin as a 2-h infusion on day 1, and bolus 400 mg/m2 of 5-fluorouracil on day 1, followed by a 22-h infusion of 600 mg/m2 of 5-fluorouracil for two consecutive days every three weeks. Topotecan was administered at a dosage of 1.5 mg/m2 by intravenous infusion daily for 5 consecutive days, starting on day 1 of a 21-day course. Both therapeutic regimens were administered continuously until there was evidence of either progressive disease (PD) or unacceptable toxicity. Prophylactic granulocyte-colony stimulating factor was only permitted for patients who developed grade 3–4 neutropenia or febrile neutropenia.\n\nTumor response was evaluated every three cycles by repeating baseline assessments using imaging studies (computed tomography and/or magnetic resonance imaging) according to the Response Evaluation Criteria in Solid Tumors (RECIST) for patients with measurable disease [23]. CA-125 was evaluated in recurrent disease using CA-125 response criteria developed by the Gynecologic Cancer InterGroup [24]. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4 [25].\n\nStatistical analysis\nAll data were analyzed by descriptive statistics. Relationships between patient characteristics were testing using the Chi-square test for categorical variables and the median test for continuous variables. The Kaplan-Meier method was used to estimate PFS and OS, with two-sided 95% confidence intervals (95%CI). PFS was defined as the time from the start of FOLFOX-4 or topotecan until disease progression or last tumor evaluation or death from any cause. OS was defined as the time from the start of FOLFOX-4 or topotecan until death from any cause or last follow-up. Survival curves were compared using the log-rank test. Due to exploratory intent, no multiple testing correction was performed. All statistical analyses were carried out with SAS statistical software, version 9.4 (SAS Institute, Cary, NC, USA). A two-sided P-value < 0.05 was deemed statistically significant for all the analyses.\n\nResults\nPatient characteristics\nThe median age was significantly different in the FOLFOX-4 and topotecan populations (60 years [range 33–85] and 66 years [range 51–80]), respectively (P = 0.032). FOLFOX-4-treated patients showed a higher incidence of abdominal and extra-abdominal metastases (18 [62.1%] vs. 6 [23.1%]) (P = 0.004). All patients had previously received a median of 4 (range 1–17) and 3 (range 1–8) cycles of FOLFOX-4 and topotecan, respectively (P = 0.038). Fourteen (48.3%) and 6 (23.1%) patients had received more than 4 treatments before FOLFOX-4 and topotecan, respectively (P = 0.055), whose 2 (range, 1–4) including a platinum-based treatment in both FOLFOX-4 and topotecan groups. Among FOLFOX-4 patients receiving a prior platinum-based treatment, we reported a recurrent and refractory disease in 19 (65.5%) and 10 (34.5%) patients, respectively, whilst we observed a recurrent and refractory cancer in 17 (64.4%) and 9 (35.6%), respectively, in the topotecan-treated patients. In the FOLFOX-4 group, a prior treatment with topotecan was reported in 4 (13.8%) patients, and only one (3.8%) patient received a prior therapy with FOLFOX-4 in the topotecan group. Among pre-treatment laboratory parameters, the incidence of neutrophil-to-lymphocyte ratio (NLR) ≥ 3 was significantly higher in patients treated with FOLFOX-4 than in those receiving topotecan (15 [53.6%] vs. 7 [28.0%]) (P = 0.013). Patient characteristics are summarized in Table 1.Table 1 Patient Characteristics\n\n\tFOLFOX-4 (n = 29)\tTopotecan (n = 26)\t\nP\n\t\n\tN (%)\tN (%)\t\t\nMedian age, years (range)\t60 (33–85)\t66 (51–80)\t0.032\t\nHistology\t\n Serous\t22 (75.9)\t22 (84.6)\t\t\n Non-serous\t7 (24.1)\t4 (15.4)\t0.422\t\nFIGO stage at presentation\t\n I-II\t3 (14.3)\t2 (12.5)\t\t\n III\t16 (76.2)\t11 (68.7)\t\t\n IV\t2 (9.5)\t3 (18.8)\t0.529\t\n Unknown/missing\t8\t10\t\t\nGrade\t\n I\t5 (20.8)\t7 (29.2)\t\t\n II\t5 (20.8)\t4 (16.7)\t\t\n III\t14 (58.4)\t13 (54.1)\t0.612\t\n Unknown/missing\t5\t2\t\t\nECOG Perfomance status\t\n 0–1\t27 (93.1)\t25 (96.1)\t\t\n 2\t2 (6.9)\t1 (3.9)\t0.622\t\nSites of metastasis\t\n Only abdominal\t11 (37.9)\t20 (76.9)\t\t\n Abdominal + extra-abdominal\t18 (62.1)\t6 (23.1)\t0.004\t\nNumber of involved sites\t\n 1\t4 (13.8)\t5 (19.2)\t\t\n 2\t10 (34.5)\t10 (38.5)\t\t\n  ≥ 3\t15 (51.7)\t11 (42.3)\t0.459\t\nMedian interval from initial diagnosis, months (range)\t47 (11.5–248)\t40.4 (9.7–1301)\t0.129\t\nLines of previous treatments\t\n  ≤ 4\t15 (51.7)\t20 (76.9)\t\t\n  > 4\t14 (48.3)\t6 (23.1)\t0.055\t\nNumber of treatment cycles\t\n Median value (range)\t4 (1–17)\t3 (1–8)\t0.038\t\nBaseline NLR\t\n  < 3\t13 (46.4)\t20 (80.0)\t\t\n  ≥ 3\t15 (53.6)\t5 (20.0)\t0.013\t\n Unknown/missing\t1\t1\t\t\nBaseline PLR\t\n  < 210\t13 (46.4)\t18 (72.0)\t\t\n  ≥ 210\t15 (53.6)\t7 (28.0)\t0.062\t\nUnknown/missing\t1\t1\t\t\nMedian baseline Hb, g/dL (range)\t11.1 (8.3–15.0)\t12.1 (8.9–14.3)\t0.058\t\nMedian baseline Ca125, ng/mL (range)\t289.9 (13.3–11,344.0)\t100.2 (12.6–10,805.0)\t0.259\t\nMedian baseline BMI, kg/m2 (range)\t23.88 (15.24–32.04)\t23.16 (19.53–30.30)\t0.345\t\nAbbreviation. BMI body mass index, ECOG Eastern Cooperative Oncology Group, FIGO International Federation of Gynecology and Obstetrics, FOLFOX-4 oxaliplatin, leucovorin, and 5-fluorouracil, Hb hemoglobin, NL ,neutrophil-to-lymphocyte ratio, PLR platelet-to-lymphocyte ratio\n\n\n\nTreatment outcomes\nAll patients treated with FOLFOX-4 and topotecan chemotherapy had measurable disease and were evaluable for tumor response by RECIST criteria (Table 2). Of the 29 patients treated with FOLFOX-4, 1 (3.5%) showed a complete response (CR), 5 (17.2%) a partial response (PR) and 8 (27.6%) stable disease (SD). Of the 26 topotecan patients, 1 (3.8%) had a CR, 1 (3.8%) a PR and 6 (23.1%) SD. Objective response was assessed by Rustin et al.’s [25] CA-125 criteria using the baseline CA-125 value as reference. Five patients treated with FOLFOX-4 and 8 with topotecan were not evaluable by Rustin’s CA-125 criteria. A CA-125 response was observed in 11 (44.0%) FOLFOX-4 patients and 5 (26.3%) topotecan patients (Table 2). The decrease in CA-125 levels was consistent with and not influenced by ascitic drainage. However, an objective radiological response (CR or PR) was not associated with CA-125 response. Median follow-up was 45 months (range 1–45) for patients treated with FOLFOX-4 and 57 months (range 1–57) for those receiving topotecan. The FOLFOX-4 group showed a median PFS and OS of 2.8 months (range 1.7–4.9) and 6.2 months (range 2.4–14.6), respectively. Topotecan patients had a median PFS and OS of 2.8 months (range 1.8–4.9) and 10.4 months (range 4.9–19.5), respectively (Table 2). A comparison of survival curves between the 2 treatment groups did not reveal a significant difference in PFS (Fig. 1) and OS (Fig. 2).Table 2 Treatment outcome\n\n\tFOLFOX-4 (n = 29)\tTopotecan (n = 26)\t\nMedian follow-up, months (range)\t45 (1–45)\t57 (1–57)\t\nMedian PFS, months (95% CI)\t2.8 (1.7–4.9)\t2.8 (1.8–4.9)\t\nMedian OS, months (95% CI)\t6.2 (2.4–14.6)\t10.4 (4.9–19.5)\t\nTumor response, n (%)\t\n CR\t1 (3.5)\t1 (3.8)\t\n PR\t5 (17.2)\t1 (3.8)\t\n SD\t8 (27.6)\t6 (23.1)\t\n PD\t15 (51.7)\t18 (69.3)\t\nCa125 response*, n (%)\t11 (44.0)\t5 (26.3)\t\nNumber of patients receiving new treatment after progression, n (%)\t16 (57.1)\t17 (65.4)\t\n*According to Rustin’s criteria\n\nAbbreviations. CR complete response, FOLFOX-4 oxaliplatin, leucovorin, and 5-fluorouracil, n number, PFS progression-free survival, PD progressive disease, PR partial response, OS overall survival, SD stable disease\n\nFig. 1 Progression-free survival (PFS) from start of FOLFOX-4 and topotecan treatments\n\nFig. 2 Overall survival (OS) from start of FOLFOX-4 and topotecan treatments\n\n\n\nUnivariate analysis did not identify any significant factors (including site of metastasis, previous treatment lines, baseline NLR and platelet-to-lymphocyte ratio [PLR]) that predicted PFS (Table 3) and OS (Table 4) within each treatment group and between patients treated with FOLFOX-4 and topotecan, with the exception of NLR, a significant predictor of OS in FOLFOX-4 (P = 0.013).Table 3 Univariate subgroups analysis of progression-free survival\n\n\tFOLFOX-4\tTOPOTECAN\t\t\nNo. patients\tNo. events\tMedian PFS (95% CI)\tNo. patients\tNo. events\tMedian PFS (95% CI)\t\nP\n\t\nSite of metastasis\t\n Only abdominal\t11\t10\t2.8 (0.6–5.6)\t20\t20\t2.7 (1.1–3.6)\t0.617\t\n Abdominal+extra-abdominal\t18\t18\t2.8 (1.7–7.0)\t6\t6\t5.0 (0.9–10.7)\t0.941\t\n P\t\t\t0.544\t\t\t0.211\t\t\nLines of previous treatments\t\n  ≤ 4\t15\t15\t2.6 (0.6–4.6)\t20\t20\t3.2 (1.6–5.4)\t0.948\t\n  > 4\t14\t13\t2.8 (1.7–8.4)\t6\t6\t2.2 (0.7–4.9)\t0.124\t\n P\t\t\t0.401\t\t\t0.054\t\t\nBaseline NLR\t\n  < 3\t13\t12\t3.0 (2.4–18.5)\t20\t20\t2.9 (1.6–5.1)\t0.142\t\n  ≥ 3\t15\t15\t1.9 (0.7–4.6)\t5\t5\t2.5 (1.0–6.6)\t0.690\t\n P\t\t\t0.075\t\t\t0.388\t\t\nBaseline PLR\t\n  < 210\t13\t12\t2.9 (0.7–18.5)\t18\t18\t2.9 (1.6–5.1)\t0.235\t\n  ≥ 210\t15\t15\t2.5 (0.9–4.6)\t7\t7\t2.5 (0.9–3.5)\t0.539\t\n P\t\t\t0.177\t\t\t0.154\t\t\nAbbreviation. FOLFOX-4 oxaliplatin, leucovorin, and 5-fluorouracil, CI confidence interval, NLR neutrophil-to-lymphocyte ratio, PFS progression-free survival, PLR platelet-to-lymphocyte ratio\n\nTable 4 Univariate subgroups analysis of overall survival\n\n\tFOLFOX-4\tTOPOTECAN\t\t\n\tNo. patients\tNo. events\tMedian PFS (95% CI)\tNo. patients\tNo. events\tMedian PFS (95% CI)\t\nP\n\t\nSite of metastasis\t\n  Only abdominal\t11\t11\t5.0 (1.3–14.6)\t20\t18\t10.4 (2.9–25.0)\t0.166\t\n  Abdominal+extra-abdominal\t18\t17\t8.2 (2.4–16.7)\t6\t6\t12.7 (2.7–23.4)\t0.919\t\n P\t\t\t0.771\t\t\t0.492\t\t\nLines of previous treatments\t\n  ≤ 4\t15\t15\t10.2 (1.3–16.7)\t20\t18\t10.5 (2.7–25.0)\t0.057\t\n  > 4\t14\t13\t5.5 (2.4–14.6)\t6\t6\t10.4 (2.9–16.2)\t0.789\t\n P\t\t\t0.753\t\t\t0.206\t\t\nBaseline NLR\t\n  < 3\t13\t12\t14.6 (3.8–22.9)\t20\t18\t10.4 (4.9–23.4)\t0.870\t\n  ≥ 3\t15\t15\t5.4 (1.2–10.2)\t5\t5\t2.9 (1.5–15.0)\t0.858\t\n P\t\t\t\n0.013\n\t\t\t\n0.051\n\t\t\nBaseline PLR\t\n  < 210\t13\t12\t13.0 (1.8–18.9)\t18\t16\t10.5 (4.9–23.3)\t0.514\t\n  ≥ 210\t15\t15\t5.6 (1.3–14.1)\t7\t7\t10.0 (1.5–15.0)\t0.660\t\n P\t\t\t0.275\t\t\t0.061\t\t\nAbbreviations. FOLFOX-4 oxaliplatin, leucovorin, and 5-fluorouracil; number; CI confidence interval, NLR neutrophils-to-lymphocyte ratio, OS overall survival, PLR platelet-to-lymphocyte ratio\n\n\n\nAt the time of analysis, 1 (3.4%) patient in the FOLFOX-4 group and 2 (7.7%) in the topotecan group were still alive. After progression on FOLFOX-4 or topotecan, 16 (57.1%) and 17 (65.4%) patients, respectively, underwent new treatments (Table 2).\n\nSafety and tolerability\nThe incidence of grade 3–4 toxicity, in particular myelotoxicity, was similar in patients treated with FOLFOX-4 and topotecan (Table 5). Ten (34.5%) and 2 (7.7%) patients reduced FOLFOX-4 and topotecan dosage due to chemotherapy-related adverse events, respectively. However, only 2 (6.9%) undergoing FOLFOX-4 and 3 (11.5%) receiving topotecan discontinued treatment because of unacceptable toxicity.Table 5 Toxicity in FOLFOX-4 and Topotecan cohorts\n\n\tFOLFOX-4 (n = 29)\tTopotecan (n = 26)\t\n\tGrade 3 n(%)\tGrade 4 n(%)\tGrade 3 n (%)\tGrade 4 n(%)\t\nAnemia\t–\t–\t2 (7.7)\t1 (3.8)\t\nNeutropenia\t3 (10.3)\t2 (6.9)\t–\t–\t\nThrombocytopenia\t1 (3.4)\t2 (6.9)\t2 (7.7)\t1 (3.8)\t\nFatigue\t1 (3.4)\t–\t1 (3.8)\t–\t\nNeurotoxicity\t–\t1 (3.4)\t–\t–\t\nHepatotoxicity\t–\t–\t1 (3.8)\t–\t\nDiarrhea\t2 (6.9)\t–\t–\t–\t\nAbbreviations. FOLFOX-4 oxaliplatin, leucovorin, and 5-fluorouracil, N number\n\n\n\nDiscussion\nDespite relatively high response rates to first-line platinum-based therapies for epithelial ovarian cancer, the majority of patients relapse and a number of treatment-related deaths have also been reported. New-generation chemotherapeutic drugs and biological agents, especially those targeting angiogenesis [26] and the nuclear enzyme poly-(ADP-ribose) polymerase (PARP) [27, 28], have recently been introduced into clinical practice, increasing the number of therapies available for relapsed or refractory disease. Consequently, patients with advanced ovarian cancer often undergo multiple chemotherapy courses in an effort to achieve long-term remission and maintain an acceptable quality of life. The main risk from using an increasing number of therapeutic agents is cumulative toxicity, especially myelotoxicity, which may influence subsequent treatments. Hence the need for new, effective and less toxic therapies in patients with recurrent and persistent disease after failure of chemotherapy.\n\nIn the present retrospective monoinstitutional study, we analyzed the results obtained in a population of ovarian cancer patients treated with FOLFOX-4 or standard topotecan monotherapy in terms of clinical impact on outcome and toxicity. The choice of therapy and dosing schedule was at the discretion of the treating physician, as was the possibility of initial dose reduction due to older age and poor performance status. Efficacy and safety were comparable in both regimens, with hematological toxicity the most frequent reason for dose reduction. Treatment discontinuation due to toxicity was rare. Despite dose limiting cumulative neurotoxicity of oxaliplatin-based therapy, only one case presented a grade 4 neurotoxicity, although grade 2 neurotoxicities had a negative impact on the quality of life in a few cases heavily pretreated with taxane- and platinum-based therapies.\n\nIn terms of response, our findings were comparable to those of other studies [19–22] on patients with measurable disease. Major limitations of this study were a small number of patients, the retrospective design, and the presence of mismatch of the cohorts related to a lack of randomization. We observed that NLR was the only prognostic factor in our patient cohort, as reported in a recent meta-analysis [29]. However, due to exploratory intent, no multiple testing correction was performed. Although adjustments for multiple comparisons can help control the study-wide false-positive rate, for exploratory analyses it is more important to judge P values cautiously than to try to formally determine their true significance level. Precise adjustment of P values and confidence intervals is often impractical in the context of exploratory research but can be useful for hypothesis-driven research.\n\nDespite all these several limitations of this study, we showed similar treatment outcomes (PFS, OS, and CA-125 response) between FOLFOX-4 and topotecan group. Specifically, there were fewer cases of PD (15 [51.7%] vs.18 [69.3%]) and a similar number of SD (8 [27.6%] vs. 6 [23.1%]) in FOLFOX-4 compared to topotecan patients. FOLFOX-4 could thus represent a potential alternative to standard chemotherapy, with a similar toxicity profile, in this patient setting. However, more recent studies [30] suggested different dose regimes of topotecan characterized by reduced number of side effects and thus this could alter the comparison of toxicities between FOLFOX-4 and topotecan profiles in our study.\n\nThe present study did not bring to light any clinical prognostic factors for PFS and OS in either treatment group, probably because of the small sample size and the lack of adequate patient selection. In addition, currently, there are no biomarkers able to improve the selection of patients candidates to FOLFOX-4 combination. Potential predictive biomarkers could derive from the analysis of homologous recombination deficiencies such as BRCA1/2 alterations, especially because they are of particular interest for platinum-based regimens. Therefore, future clinical trials in this disease setting could be supported by genomic and proteomic studies to identify prognostic factors associated with response to fluorouracil. The advances made in genetic and molecular biology could provide a valuable insight into the alterations underlying these types of ovarian cancer, and the relationship between the mechanism of action of fluorouracil and the subsequent downstream molecular pathways activated during tumorigenesis and disease progression.\n\nConclusion\nThe retrospective nature of our study and the small sample size do not allow for definitive conclusions to be drawn. However, our results provide further evidence that the FOLFOX-4 regimen may be as effective as standard monotherapies and could be proposed as an appropriate salvage treatment in refractory or resistant ovarian cancer. However, it should be appropriate to consider these heavily-pretreated patients as an ideal group for clinical trials; particularly given the success or emerging data of some newer classes of targeted therapies such as PARP inhibitors, antivascular drugs, dual antibody like molecules, antibody drug conjugates and so randomized multicenter trials comparing the FOLFOX-4 regimen, alone or, particularly, in combination with targeted therapy, are warranted to improve the standard of care in patients with heavily-pretreated disease.\n\nAbbreviations\n95%CI95% confidence interval\n\nCA-125cancer antigen 125\n\nCRcomplete response\n\nCTCAECommon Terminology Criteria for Adverse Events\n\nECOGEastern Cooperative Oncology Group\n\nFOLFOX-4oxaliplatin plus leucovorin and 5-fluorouracil\n\nNLRneutrophil-to-lymphocyte ratio\n\nOSoverall survival\n\nPARPpoly(ADP-ribose) polymerase\n\nPDprogressive disease\n\nPFSprogression-free survival\n\nPLRplatelet-to-lymphocyte ratio\n\nRECISTResponse Evaluation Criteria in Solid Tumors\n\nSDstable disease\n\nAcknowledgements\nThe authors wish to thank Gráinne Tierney for editorial assistance.\n\nFunding\nNo funding was received for this study.\n\nAvailability of data and materials\nThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\n\nAuthors’ contributions\nVC and UDG was involved in the conception of the study, acquisition and analysis of the data, and wrote the first draft of the manuscript. VC, GG, LR, CL, GS, AF, DDL, SLB and CM were responsible for data acquisition. UDG and DA were involved in the conception and design of the study. CV, ES and UDG contributed to data analysis and interpretation of data. VC, ES, VG, AA, LL, MPC and UDG critically revised the manuscript for important intellectual content. VC and ES participated in analyzing the results and drafting the manuscript. All authors read and approved the final manuscript.\n\nEthics approval and consent to participate\nThis study was reviewed and approved by the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS Institutional Review Board Ethics Committee (REC 5485/2018). It was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki, and all the patients provided written informed consent.\n\nConsent for publication\nNot applicable.\n\nCompeting interests\nVC and UDG have received speaker honoraria or travel support from Astellas, Janssen-Cilag, Bayer, Ipsen and Sanofi-Aventis. The other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.\n\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n1. Jemal A Bray F Center MM Ferlay J Ward E Forman D Cancer statistics, 2011 CA Cancer J Clin 2011 61 69 90 10.3322/caac.20107 21296855 \n2. Hennessy BT, Coleman RL, Markman M. Ovarian cancer. Lancet 2009;17;374(9698):1371–1382.\n3. Pignata S Cecere S Du Bois A Harter P Heitz F Treatment of recurrent ovarian cancer Ann Oncol 2017 8 Suppl 8 viii51 viii56 10.1093/annonc/mdx441 \n4. Raymond E Chaney SG Taamma A Cvitkovic E Oxaliplatin: a review of preclinical and clinical studies Ann Oncol 1998 9 1053 1071 10.1023/A:1008213732429 9834817 \n5. Rixe O Ortuzar W Alvarez M Parker R Reed E Paull K Oxaliplatin, tetraplatin, cisplatin, and carboplatin: spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute's anticancer drug screen panel Biochem Pharmacol 1996 52 1855 1865 10.1016/S0006-2952(97)81490-6 8951344 \n6. Chollet P Bensmaine MA Brienza S Deloche C Curé H Caillet H Single agent activity of oxaliplatin in heavily pretreated advanced epithelial ovarian cancer Ann Oncol 1996 7 1065 1070 10.1093/oxfordjournals.annonc.a010500 9037366 \n7. Soulie P Bensmaine A Garrino C Chollet P Brain E Fereres M Oxaliplatin/cisplatin (l-OHP/CDDP) combination in heavily pretreated ovarian cancer Eur J Cancer 1997 33 1400 1406 10.1016/S0959-8049(97)00122-6 9337681 \n8. Piccart MJ Green JA Lacave AJ Oxaliplatin or paclitaxel in patients with platinum-pretreated advanced ovarian cancer: a randomized phase II study of the European Organization for Research and Treatment of Cancer gynecology group J Clin Oncol 2000 18 1193 1202 10.1200/JCO.2000.18.6.1193 10715288 \n9. Fracasso PM Blessing JA Morgan MA Sood AK Hoffman JS Phase II study of oxaliplatin in platinum-resistant and refractory ovarian cancer: a gynecologic group study J Clin Oncol 2003 21 2856 2859 10.1200/JCO.2003.03.077 12885801 \n10. Prefontaine M Donovan JT Powell JL Buley L Treatment of refractory ovarian cancer with 5-fluorouracil and leucovorin Gynecol Oncol 1996 61 249 252 10.1006/gyno.1996.0134 8626142 \n11. Morgan RJ Jr Speyer J Doroshow JH Margolin K Raschko J Sorich J Modulation of 5-fluorouracil with high-dose leucovorin calcium: activity in ovarian cancer and correlation with CA-125 levels Gynecol Oncol 1995 58 79 85 10.1006/gyno.1995.1187 7789895 \n12. Look KY Muss HB Blessing JA Morris M A phase II trial of 5-fluorouracil and high-dose leucovorin in recurrent epithelial ovarian carcinoma A Gynecologic Oncology Group Study Am J Clin Oncol 1995 18 9 22 \n13. Kamphuis JT Huider MC Ras GJ Verhagen CA Kateman I Vreeswijk JH High-dose 5-fluorouracil and leucovorin as second-line chemotherapy in patients with platinum resistant epithelial ovarian cancer Cancer Chemother Pharmacol 1995 37 190 192 10.1007/BF00685649 7497592 \n14. Long HJ 3rd Nelimark RA Su JQ Garneau SC Levitt R Goldberg RM Phase II evaluation of 5-fluorouracil and low-dose leucovorin in cisplatin-refractory advanced ovarian carcinoma Gynecol Oncol 1994 54 180 183 10.1006/gyno.1994.1190 8063243 \n15. Raymond E Buquet-Fagot C Djelloul S Mester J Cvitkovic E Allain P Antitumor activity of oxaliplatin in combination with 5-fluorouracil and the thymidylate synthase inhibitor AG337 in human colon, breast and ovarian cancers Anti-Cancer Drugs 1997 8 876 885 10.1097/00001813-199710000-00009 9402315 \n16. Goldberg RM Sargent DJ Morton RF Fuchs CS Ramanathan RK Williamson SK A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer J Clin Oncol 2004 22 23 30 10.1200/JCO.2004.09.046 14665611 \n17. Pectasides D Pectasides M Farmakis D Bountouroglou N Nikolaou M Koumpou M Oxaliplatin plus high-dose leucovorin and 5- fluorouracil in pretreated advanced breast cancer: a phase II study Ann Oncol 2003 14 537 542 10.1093/annonc/mdg172 12649097 \n18. Kim YS Hong J Sym SJ Park SH Park J Cho EK Oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX-4) combination chemotherapy as a salvage treatment in advanced gastric cancer Cancer Res Treat 2010 42 24 29 10.4143/crt.2010.42.1.24 20369048 \n19. Sundar S Symonds RP Decatris MP Kumar DM Osman A Vasanthan S Phase II trial of oxaliplatin and 5-fluorouracil/leucovorin combination in epithelial ovarian carcinoma relapsing within 2 years of platinum-based therapy Gynecol Oncol 2004 94 502 508 10.1016/j.ygyno.2004.04.020 15297195 \n20. Pectasides D Pectasides M Farmakis D Gaglia A Koumarianou A Nikolaou M Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: a phase II study Gynecol Oncol 2004 95 165 172 10.1016/j.ygyno.2004.06.029 15385127 \n21. Rosa DD Awada A Mano MS Selleslags J Lebrun F Gil T Oxaliplatin/5fluorouracil-based chemotherapy was active and well tolerated in heavily pretreated patients with ovarian carcinoma Arch Gynecol Obstet 2008 278 457 462 10.1007/s00404-008-0592-9 18273626 \n22. Lee HJ Kim HS Park NH Chung HH Kim JW Song YS Feasibility of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in heavily pretreated patients with recurrent epithelial ovarian cancer Cancer Res Treat 2013 45 40 47 10.4143/crt.2013.45.1.40 23613669 \n23. Eisenhauer EA Therasse P Bogaerts J Schwartz LH Sargent D Ford R New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer 2009 452 228 224 10.1016/j.ejca.2008.10.026 \n24. Rustin GJ Vergote I Eisenhauer E Pujade-Lauraine E Quinn M Thigpen T Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the gynecological Cancer Intergroup (GCIG) Int J Gynecol Cancer 2011 21 419 423 10.1097/IGC.0b013e3182070f17 21270624 \n25. Cancer Therapy Evaluation Program. Common terminology criteria for adverse events, version 3.0 [Internet]. Bethesda: National Cancer Institute; 2003 [cited 2012 Nov 1]. Available from: http://ctep.cancer.gov/forms/CTCAEv4.pdf\n26. Conteduca V Kopf B Burgio SL Bianchi E Amadori D De Giorgi U The emerging role of anti-angiogenic therapy in ovarian cancer (review) Int J Oncol 2014 44 1417 1424 10.3892/ijo.2014.2334 24626312 \n27. Cancer Genome Atlas Research Network Integrated genomic analyses of ovarian carcinoma Nature 2011 474 609 615 10.1038/nature10166 21720365 \n28. Hoeijmakers JH DNA damage, aging, and cancer N Engl J Med 2009 361 1475 1485 10.1056/NEJMra0804615 19812404 \n29. Zhu Y Zhou S Liu Y Zhai L Sun X Prognostic value of systemic inflammatory markers in ovarian Cancer: a PRISMA-compliant meta-analysis and systematic review BMC Cancer 2018 18 1 443 10.1186/s12885-018-4318-5 29669528 \n30. Peng LH Chen XY Wu TX Topotecan for ovarian cancer Cochrane Database Syst Rev 2008 2 CD005589\n\n", "fulltext_license": "CC BY", "issn_linking": "1471-2407", "issue": "18(1)", "journal": "BMC cancer", "keywords": "FOLFOX-4; Fluorouracil; Ovarian cancer; Platinum resistance; Survival; Topotecan", "medline_ta": "BMC Cancer", "mesh_terms": "D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D019008:Drug Resistance, Neoplasm; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005472:Fluorouracil; D006801:Humans; D002955:Leucovorin; D008875:Middle Aged; D009944:Organoplatinum Compounds; D010051:Ovarian Neoplasms; D000077982:Progression-Free Survival; D016879:Salvage Therapy", "nlm_unique_id": "100967800", "other_id": null, "pages": "1267", "pmc": null, "pmid": "30567527", "pubdate": "2018-12-19", "publication_types": "D016428:Journal Article", "references": "10715288;12649097;12885801;14665611;15297195;15385127;18273626;18425923;19097774;19793610;19812404;20369048;21270624;21296855;21720365;23613669;24626312;29232464;29669528;7497592;7789895;7847253;8063243;8626142;8951344;9037366;9337681;9402315;9834817", "title": "Oxaliplatin plus leucovorin and 5-fluorouracil (FOLFOX-4) as a salvage chemotherapy in heavily-pretreated platinum-resistant ovarian cancer.", "title_normalized": "oxaliplatin plus leucovorin and 5 fluorouracil folfox 4 as a salvage chemotherapy in heavily pretreated platinum resistant ovarian cancer" }

[ { "companynumb": "IT-TEVA-2019-IT-1007509", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": "022160", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 HOUR INFUSION ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "85", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEUCOVORIN" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": "71198", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 HOUR INFUSION ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FOLINIC ACID" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": "40333", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "BOLUS ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": "40333", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "22 HOUR INFUSION FOR TWO CONSECUTIVE DAYS; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neurotoxicity", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CONTEDUCA V, GURIOLI G, ROSSI L, SCARPI E, LOLLI C, SCHEPISI G, ET AL. OXALIPLATIN PLUS LEUCOVORIN AND 5-FLUOROURACIL (FOLFOX-4) AS A SALVAGE CHEMOTHERAPY IN HEAVILY-PRETREATED PLATINUM-RESISTANT OVARIAN CANCER. BMC-CAN 2018?18:1267.", "literaturereference_normalized": "oxaliplatin plus leucovorin and 5 fluorouracil folfox 4 as a salvage chemotherapy in heavily pretreated platinum resistant ovarian cancer", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20190207", "receivedate": "20190207", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15934897, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190417" }, { "companynumb": "IT-SUN PHARMACEUTICAL INDUSTRIES LTD-2019RR-198213", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "202922", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "85 MILLIGRAM/SQ. METER, AS A 2-H INFUSION ON DAY 1", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "85", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEUCOVORIN" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": "1200 MILLIGRAM/SQ. METER AS A 2-H INFUSION ON DAY 1", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUCOVORIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MILLIGRAM/SQ. METER 22-H INFUSION FOR TWO CONSECUTIVE DAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "5-FLUOROURACIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "040", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MILLIGRAM/SQ. METER ON DAY ONE", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "5-FLUOROURACIL" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Nephropathy toxic", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CONTEDUCA V, GURIOLI G, ROSSI L, SCARPI E, LOLLI C, SCHEPISI G, ET AL. OXALIPLATIN PLUS LEUCOVORIN AND 5-FLUOROURACIL (FOLFOX-4) AS A SALVAGE CHEMOTHERAPY IN HEAVILY-PRETREATED PLATINUM-RESISTANT OVARIAN CANCER. BMC CAN. 2018?19 DEC? 18(1):1267", "literaturereference_normalized": "oxaliplatin plus leucovorin and 5 fluorouracil folfox 4 as a salvage chemotherapy in heavily pretreated platinum resistant ovarian cancer", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20190205", "receivedate": "20190205", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15916967, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190417" }, { "companynumb": "IT-MYLANLABS-2019M1007528", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEUCOVORIN" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "2 HOUR INFUSION ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FOLINIC ACID" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "2 HOUR INFUSION ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "85", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": "202668", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "BOLUS ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": "202668", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "22 HOUR INFUSION FOR TWO CONSECUTIVE DAYS; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fatigue", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CONTEDUCA V, GURIOLI G, ROSSI L, SCARPI E, LOLLI C, SCHEPISI G, ET AL. OXALIPLATIN PLUS LEUCOVORIN AND 5-FLUOROURACIL (FOLFOX-4) AS A SALVAGE CHEMOTHERAPY IN HEAVILY-PRETREATED PLATINUM-RESISTANT OVARIAN CANCER. BMC-CAN 2018?18:1267.", "literaturereference_normalized": "oxaliplatin plus leucovorin and 5 fluorouracil folfox 4 as a salvage chemotherapy in heavily pretreated platinum resistant ovarian cancer", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20190129", "receivedate": "20190129", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15885256, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190417" }, { "companynumb": "IT-TEVA-2019-IT-1007510", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "40333", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "22 HOUR INFUSION FOR TWO CONSECUTIVE DAYS; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "022160", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 HOUR INFUSION ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "85", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEUCOVORIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "71198", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 HOUR INFUSION ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FOLINIC ACID" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "40333", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "BOLUS ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fatigue", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CONTEDUCA V, GURIOLI G, ROSSI L, SCARPI E, LOLLI C, SCHEPISI G, ET AL. OXALIPLATIN PLUS LEUCOVORIN AND 5-FLUOROURACIL (FOLFOX-4) AS A SALVAGE CHEMOTHERAPY IN HEAVILY-PRETREATED PLATINUM-RESISTANT OVARIAN CANCER. BMC-CAN 2018?18:1267.", "literaturereference_normalized": "oxaliplatin plus leucovorin and 5 fluorouracil folfox 4 as a salvage chemotherapy in heavily pretreated platinum resistant ovarian cancer", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20190207", "receivedate": "20190207", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15934886, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190417" }, { "companynumb": "IT-PFIZER INC-2018530840", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEUCOVORIN CALCIUM" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200 MG/M2, EVERY 3 WEEKS, (2-H INFUSION ON DAY 1)", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN CANCER", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEUCOVORIN CALCIUM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "078813", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "85 MG/M2, EVERY 3 WEEKS, (2-H INFUSION ON DAY 1)", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN CANCER", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "85", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "600 MG/M2, EVERY 3 WEEKS, (22-H INFUSION, FOR TWO CONSECUTIVE DAYS)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "5-FLUOROURACIL [FLUOROURACIL]" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "040", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400 MG/M2, EVERY 3 WEEKS, (ON DAY 1)", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN CANCER", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "5-FLUOROURACIL [FLUOROURACIL]" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neurotoxicity", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CONTEDUCA, V.. OXALIPLATIN PLUS LEUCOVORIN AND 5-FLUOROURACIL (FOLFOX-4) AS A SALVAGE CHEMOTHERAPY IN HEAVILY-PRETREATED PLATINUM-RESISTANT OVARIAN CANCER. BMC CANCER. 2018?18 (1):10.1186/S12885-018-5180-1", "literaturereference_normalized": "oxaliplatin plus leucovorin and 5 fluorouracil folfox 4 as a salvage chemotherapy in heavily pretreated platinum resistant ovarian cancer", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20181231", "receivedate": "20181231", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15776560, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" }, { "companynumb": "IT-MYLANLABS-2019M1007518", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LEUCOVORIN" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": "203800", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "2 HOUR INFUSION ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FOLINIC ACID" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "BOLUS ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "400", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "2 HOUR INFUSION ON DAY 1; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN EPITHELIAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "85", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "22 HOUR INFUSION FOR TWO CONSECUTIVE DAYS; EVERY THREE WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Neurotoxicity", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "CONTEDUCA V, GURIOLI G, ROSSI L, SCARPI E, LOLLI C, SCHEPISI G, ET AL. OXALIPLATIN PLUS LEUCOVORIN AND 5-FLUOROURACIL (FOLFOX-4) AS A SALVAGE CHEMOTHERAPY IN HEAVILY-PRETREATED PLATINUM-RESISTANT OVARIAN CANCER. BMC-CAN 2018?18:1267.", "literaturereference_normalized": "oxaliplatin plus leucovorin and 5 fluorouracil folfox 4 as a salvage chemotherapy in heavily pretreated platinum resistant ovarian cancer", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20190129", "receivedate": "20190129", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15885241, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190417" } ]

{ "abstract": "Current therapeutic options for patients with extracranial head and neck arteriovenous malformations are limited. Surgical intervention, such as sclerotherapy or resection, often result in rapid recurrence and progression of disease.\n\n\n\nTo assess the efficacy and tolerability of sirolimus as an adjuvant therapy for endovascular embolization in the management of complicated extracranial head and neck arteriovenous malformations.\n\n\n\nThis case series examined 6 patients with extracranial head and neck arteriovenous malformations treated from January 1, 2013, to December 31, 2017, at a multidisciplinary vascular anomalies clinic within Stanford Hospital and Clinics.\n\n\n\nInitiation of sirolimus at least 1 month prior to endovascular embolization, targeting a trough level of 10 to 15 ng/mL throughout the course of the endovascular embolization series and continued for at least 1 month after the series.\n\n\n\nClinical manifestations; disease progression and overall response to treatment were assessed via clinical evaluation and radiographic imaging.\n\n\n\nAll 6 patients (4 male and 2 female patients; mean age, 24.5 years [range, 9-44 years]) responded favorably to the combination of sirolimus therapy followed by endovascular embolization, and 4 patients exhibited a near-complete response. The median duration of follow-up was 19 months (range, 6-40 months). One patient discontinued sirolimus soon after embolization and experienced regrowth of the arteriovenous malformation after 1 year. Sirolimus was resumed, which has stabilized his disease for more than 2 years. Mild adverse effects were noted in 4 patients. The combination therapy was well tolerated in all patients. One patient developed skin ulceration after embolization and required surgical debridement. Another patient developed pulmonary microthrombi after embolization with cyanoacrylate glue that resolved with a brief course of anti-inflammatory therapy.\n\n\n\nAlthough further prospective trials are needed, this report suggests the benefit of a mammalian target of rapamycin inhibitor as an adjuvant therapy for surgical embolization of complex, extracranial head and neck arteriovenous malformations. The optimal dosing and therapeutic duration of sirolimus treatment before and after embolization remain to be determined.", "affiliations": "Stanford School of Medicine, Stanford, California.;Department of Radiology, Stanford University School of Medicine, Palo Alto, California.;Department of Dermatology, West Virginia University, Morgantown.;Department of Dermatology, Baylor College of Medicine, Houston, Texas.;Department of Hematology, Stanford University School of Medicine, Palo Alto, California.;Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Palo Alto, California.;Department of Otolaryngology, Stanford University School of Medicine, Palo Alto, California.;Department of Dermatology, Stanford University School of Medicine, Palo Alto, California.;Department of Dermatology, Stanford University School of Medicine, Palo Alto, California.", "authors": "Chelliah|Malcolm Pyles|MP|;Do|Huy M|HM|;Zinn|Zachary|Z|;Patel|Viraat|V|;Jeng|Michael|M|;Khosla|Rohit K|RK|;Truong|Mai-Thy|MT|;Marqueling|Ann|A|;Teng|Joyce M C|JMC|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1001/jamadermatol.2018.3039", "fulltext": null, "fulltext_license": null, "issn_linking": "2168-6068", "issue": "154(11)", "journal": "JAMA dermatology", "keywords": null, "medline_ta": "JAMA Dermatol", "mesh_terms": "D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001165:Arteriovenous Malformations; D002648:Child; D004621:Embolization, Therapeutic; D005260:Female; D006257:Head; D006801:Humans; D008297:Male; D009333:Neck; D015911:Sclerotherapy; D055815:Young Adult", "nlm_unique_id": "101589530", "other_id": null, "pages": "1316-1319", "pmc": null, "pmid": "30326494", "pubdate": "2018-11-01", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "21445948;11821896;27723921;11844242;26783326;28190454;16904613;26049824;15854255;24038909;18370913;20335868", "title": "Management of Complex Arteriovenous Malformations Using a Novel Combination Therapeutic Algorithm.", "title_normalized": "management of complex arteriovenous malformations using a novel combination therapeutic algorithm" }

[ { "companynumb": "US-DRREDDYS-USA/USA/18/0106250", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "SIROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "201578", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ARTERIOVENOUS MALFORMATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SIROLIMUS." } ], "patientagegroup": null, "patientonsetage": "32", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Oral mucosa erosion", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "TENG J, DO H, ZINN Z, PATEL V, JENG M, KHOSLA R, TRUONG M, MARQUELING A, CHELLIAH M. MANAGEMENT OF COMPLEX ARTERIOVENOUS MALFORMATIONS USING A NOVEL COMBINATION THERAPEUTIC ALGORITHM. JAMA DERMATOLOGY. 2018?154(11):1316-1319.", "literaturereference_normalized": "management of complex arteriovenous malformations using a novel combination therapeutic algorithm", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181231", "receivedate": "20181231", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15776204, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190205" }, { "companynumb": "US-PFIZER INC-2018406544", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "SIROLIMUS" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "021110", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK (AFTER EMBOLIZATION)", "drugenddate": null, "drugenddateformat": null, "drugindication": "EAR MALFORMATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SIROLIMUS." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "SIROLIMUS" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "021110", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK (1 MONTH BEFORE THEIR FIRST EMBOLIC PROCEDURE, WITH A TARGET TROUGH LEVEL OF 10 TO 15NG/ML)", "drugenddate": null, "drugenddateformat": null, "drugindication": "ARTERIOVENOUS MALFORMATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SIROLIMUS." } ], "patientagegroup": null, "patientonsetage": "44", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Skin ulcer", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "CHELLIAH, M.. MANAGEMENT OF COMPLEX ARTERIOVENOUS MALFORMATIONS USING A NOVEL COMBINATION THERAPEUTIC ALGORITHM. JAMA DERMATOLOGY. 2018?154(11):1316-1319", "literaturereference_normalized": "management of complex arteriovenous malformations using a novel combination therapeutic algorithm", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20191007", "receivedate": "20181012", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15494209, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200122" }, { "companynumb": "US-DRREDDYS-USA/USA/18/0106249", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "SIROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "201578", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ARTERIOVENOUS MALFORMATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SIROLIMUS." } ], "patientagegroup": null, "patientonsetage": "33", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Oral mucosa erosion", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "TENG J, DO H, ZINN Z, PATEL V, JENG M, KHOSLA R, TRUONG M, MARQUELING A, CHELLIAH M. MANAGEMENT OF COMPLEX ARTERIOVENOUS MALFORMATIONS USING A NOVEL COMBINATION THERAPEUTIC ALGORITHM. JAMA DERMATOLOGY. 2018 SEP 19?154(11):1316-1319.", "literaturereference_normalized": "management of complex arteriovenous malformations using a novel combination therapeutic algorithm", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181231", "receivedate": "20181231", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15776192, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190205" }, { "companynumb": "US-DRREDDYS-USA/USA/18/0106247", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "SIROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "201578", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ARTERIOVENOUS MALFORMATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SIROLIMUS." } ], "patientagegroup": null, "patientonsetage": "16", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Oral mucosa erosion", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pulmonary embolism", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "TENG J, DO H, ZINN Z, PATEL V, JENG M, CHELLIAH M, KHOSLA R, TRUONG M, MARQUELING A. MANAGEMENT OF COMPLEX ARTERIOVENOUS MALFORMATIONS USING A NOVEL COMBINATION THERAPEUTIC ALGORITHM. JAMA DERMATOLOGY. 2018 SEP 19?154(11):1316-1319.", "literaturereference_normalized": "management of complex arteriovenous malformations using a novel combination therapeutic algorithm", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181221", "receivedate": "20181221", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15748122, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" }, { "companynumb": "US-DRREDDYS-USA/USA/18/0106229", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "SIROLIMUS" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "201578", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ARTERIOVENOUS MALFORMATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SIROLIMUS." } ], "patientagegroup": null, "patientonsetage": "44", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Skin ulcer", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Oral mucosa erosion", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Skin infection", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "TENG J, DO H, ZINN Z, PATEL V, JENG M, KHOSLA R, TRUONG M, MARQUELING A, CHELLIAH M. MANAGEMENT OF COMPLEX ARTERIOVENOUS MALFORMATIONS USING A NOVEL COMBINATION THERAPEUTIC ALGORITHM. JAMA DERMATOLOGY. 2018?154(11):1316-1319.", "literaturereference_normalized": "management of complex arteriovenous malformations using a novel combination therapeutic algorithm", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181231", "receivedate": "20181231", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15776190, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190205" }, { "companynumb": "US-DRREDDYS-USA/USA/18/0106251", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "SIROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "201578", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ARTERIOVENOUS MALFORMATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SIROLIMUS." } ], "patientagegroup": null, "patientonsetage": "13", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pruritus", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "TENG J, DO H, ZINN Z, PATEL V, JENG M, KHOSLA R, TRUONG M, MARQUELING A, CHELLIAH M. MANAGEMENT OF COMPLEX ARTERIOVENOUS MALFORMATIONS USING A NOVEL COMBINATION THERAPEUTIC ALGORITHM. JAMA DERMATOLOGY. 2018?154(11):1316-1319.", "literaturereference_normalized": "management of complex arteriovenous malformations using a novel combination therapeutic algorithm", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181231", "receivedate": "20181231", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15776321, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190205" }, { "companynumb": "US-DRREDDYS-USA/USA/18/0106248", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "SIROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "201578", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ARTERIOVENOUS MALFORMATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SIROLIMUS." } ], "patientagegroup": null, "patientonsetage": "9", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Oral mucosa erosion", "reactionmeddraversionpt": "21.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "TENG J, DO H, ZINN Z, PATEL V, JENG M, KHOSLA R, TRUONG M, MARQUELING A, CHELLIAH M. MANAGEMENT OF COMPLEX ARTERIOVENOUS MALFORMATIONS USING A NOVEL COMBINATION THERAPEUTIC ALGORITHM. JAMA DERMATOLOGY. 2018?154(11):1316-1319.", "literaturereference_normalized": "management of complex arteriovenous malformations using a novel combination therapeutic algorithm", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181231", "receivedate": "20181231", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15776191, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190205" } ]

{ "abstract": "Systemic lupus erythematosus (SLE)-associated haemophagocytic lymphohistiocytosis (HLH) is called acute lupus haemophagocytic syndrome (ALHS), which is relatively rare but life-threatening. We present the case of a 43-year-old woman diagnosed with SLE with panniculitis, pleuritis, and autoimmune hepatitis. She was treated with high-dose glucocorticoids. Although disease activity temporarily improved, she developed fever, elevation of liver enzymes, hyperferritinemia, severe inflammatory response, and thrombocytopenia a month after starting glucocorticoids. Bone marrow biopsy was performed and haemophagocytosis was observed. She was diagnosed with ALHS on day 49. Since she developed ALHS during administration of glucocorticoids, her ALHS was determined to be refractory to glucocorticoid monotherapy; therefore, additional immunosuppressive agents were needed. She was treated with methylprednisolone pulse, plasma exchange and cyclosporine A (CyA). However, CyA was discontinued on day 54 because CyA-induced hypertensive encephalopathy was suspected. Subsequently, rituximab (RTX) was introduced to treat refractory ALHS on day 56; the disease activity subsequently reduced. After four courses of RTX, her ferritin levels and platelet counts were within the normal range and the glucocorticoid dose could be tapered to betamethasone 2.0 mg/day on day 132. No subsequent recurrence of SLE and ALHS was observed until day 132. RTX might therefore be an effective therapeutic option for refractory ALHS.", "affiliations": "Department of Rheumatology, Yokohama Rosai Hospital, Yokohama, Japan.;Department of Rheumatology, Yokohama Rosai Hospital, Yokohama, Japan.;Department of Rheumatology, Yokohama Rosai Hospital, Yokohama, Japan.;Department of Rheumatology, Yokohama Rosai Hospital, Yokohama, Japan.;Department of Rheumatology, Yokohama Rosai Hospital, Yokohama, Japan.", "authors": "Tomofuji|Yoshihiko|Y|;Ishikawa|Yuichi|Y|0000-0002-9594-5845;Hattori|Koto|K|;Fujiwara|Michio|M|;Kita|Yasuhiko|Y|", "chemical_list": "D018501:Antirheumatic Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D000069283:Rituximab", "country": "England", "delete": false, "doi": "10.1080/24725625.2019.1705529", "fulltext": null, "fulltext_license": null, "issn_linking": "2472-5625", "issue": "4(2)", "journal": "Modern rheumatology case reports", "keywords": "B cells; Systemic lupus erythematosus; acute lupus haemophagocytic syndrome; haemophagocytic lymphohistiocytosis; rituximab", "medline_ta": "Mod Rheumatol Case Rep", "mesh_terms": "D000328:Adult; D018501:Antirheumatic Agents; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D007166:Immunosuppressive Agents; D008180:Lupus Erythematosus, Systemic; D051359:Lymphohistiocytosis, Hemophagocytic; D058990:Molecular Targeted Therapy; D000069283:Rituximab; D063189:Symptom Assessment; D016896:Treatment Outcome", "nlm_unique_id": "101761026", "other_id": null, "pages": "222-228", "pmc": null, "pmid": "33087000", "pubdate": "2020-07", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Successful treatment of refractory acute lupus haemophagocytic syndrome using rituximab: a case report.", "title_normalized": "successful treatment of refractory acute lupus haemophagocytic syndrome using rituximab a case report" }

[ { "companynumb": "JP-SUN PHARMACEUTICAL INDUSTRIES LTD-2020R1-254078", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOSPORINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "210913", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CICLOSPORIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." } ], "patientagegroup": null, "patientonsetage": "43", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haemophagocytic lymphohistiocytosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypertensive encephalopathy", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "TOMOFUJI Y, ISHIKAWA Y, HATTORI K, FUJIWARA M, KITA Y. SUCCESSFUL TREATMENT OF REFRACTORY ACUTE LUPUS HAEMOPHAGOCYTIC SYNDROME USING RITUXIMAB: A CASE REPORT. MOD RHEUMATOL CASE REP. 2020?4(2):222?228", "literaturereference_normalized": "successful treatment of refractory acute lupus haemophagocytic syndrome using rituximab a case report", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20200727", "receivedate": "20200727", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18078733, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" } ]

{ "abstract": "Cutaneous adverse events are common with the use of immunotherapy. Although only 5% of patients develop severe reactions, about half will develop mild to moderate cutaneous adverse events. Vitiligo has been seen in melanomas treated with checkpoint inhibitors (CPI). We describe the first known case of Vitiligoid irAE (immune-related adverse event) in a non-melanoma solid cancer treated with pembrolizumab.", "affiliations": "Division of Internal Medicine, Department of Hematology/Oncology, Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX, USA.", "authors": "Bulbul|Ajaz|A|0000-0002-2728-8468", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1093/omcr/omz016", "fulltext": "\n==== Front\nOxf Med Case ReportsOxf Med Case ReportsomcrOxford Medical Case Reports2053-8855Oxford University Press 10.1093/omcr/omz016omz016Case ReportVitiligoid hypopigmentation associated with pembrolizumab in metastatic head and neck cancer http://orcid.org/0000-0002-2728-8468Bulbul Ajaz 121 Division of Internal Medicine, Department of Hematology/Oncology, Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX, USA2 Department of Internal Medicine, Department of Hematology/Oncology, University of New Mexico, NM, USACorrespondence address. Department of Internal Medicine, Department of Hematology/Oncology, University of New Mexico, 101 S Canal St, Carlsbad, NM 88220, USA. Tel: +1-505-504-8731; E-mail: ajazbulbul@gmail.com3 2019 29 3 2019 29 3 2019 2019 3 omz01630 1 2019 04 2 2019 12 2 2019 © The Author(s) 2019. Published by Oxford University Press.2019This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comAbstract\nCutaneous adverse events are common with the use of immunotherapy. Although only 5% of patients develop severe reactions, about half will develop mild to moderate cutaneous adverse events. Vitiligo has been seen in melanomas treated with checkpoint inhibitors (CPI). We describe the first known case of Vitiligoid irAE (immune-related adverse event) in a non-melanoma solid cancer treated with pembrolizumab.\n\nVitiligopembrolizumabhypopigmentationirAE\n==== Body\nCASE REPORT\nA 32-year-old man with stage IVA T2N2M0 squamous cell cancer of the tonsil (p16 positive) was initially treated with induction Docetaxel Carboplatin and 5FU followed by carboplatin and XRT to 70 Gy achieved a complete response in August 2015. In January 2017, he had a metastatic recurrence with a 1.7 × 1.3 cm right upper lobe lesion and 2.3 × 1.4 cm right paratracheal lesion. PD-L1 IHC showed high (90%) expression. The patient received pembrolizumab between February 2017 and February 2018 achieving an early complete response within 2 months of his treatment with no eventful grade three toxicities except for immune-mediated hypothyroidism which was managed with levothyroxine. His medical history was negative for any skin disorders or skin cancers.\n\nFive months after stopping his treatment he noticed two solitary hypopigmented vitiliginous patches (Fig. 1) and a small cluster of hyperpigmented lesions (Fig. 2) one on his left preauricular area and the other on the right angle of his mouth. No preceding erythema was noted. The lesions were non-pruritic. His most recent imaging in July 2018 continues to show no evidence of disease. A skin punch biopsy of the hypopigmented lesions was sent for pathological analysis (Figs 3–5). Morphological description of (hematoxylin–eosin) HE findings showed mild epidermal acanthosis, parakeratosis, and some interface dermatitis with few dyskeratotic cells and underlying lymphocytic infiltrate with scattered dermal melanophages. Immunohistochemical (IHC) Fontana stain, negative SOX10 stain identifies no argentaffin granules and melanin or melanoma making this consistent with a vitiligo lesion morphologically appearing to be immunotherapy related.\n\nFigure 1: Clinical photograph of the angle of the mouth with hypopigmented patch.\n\nFigure 2: Clinical photograph of hyperpigmented macules preceding hypopigmentation lower extremity with hypopigmented lesions.\n\nFigure 3: Skin biopsy (hematoxylin–eosin stain, original magnification ×20). Mild epidermal acanthosis, focal parakeratosis and interface dermatitis lymphocytic infiltrate with scattered dermal melanophages.\n\nFigure 4: IHC Fontana stain identifies no argentaffin granules and melanin.\n\nFigure 5: Negative SOX10 stain (melanoma marker).\n\nDISCUSSION\nCutaneous adverse events are common with the use of immunotherapy. Although only 5% of patients develop severe reactions, about half will develop mild to moderate cutaneous adverse events [1]. Vitiligoid irAE (immune-related adverse event) in a non-melanoma solid cancer has not been commonly described in literature when treated with pembrolizumab.\n\nThe development of vitiligo represents a well-recognized adverse event in patients with melanoma treated with anti-CTLA-4 and anti-programmed death (PD-1)/programmed death ligand (PD-L1) antibodies. Depigmentation may result from induction of antimelanoma immunity through a cytotoxic T-cell-mediated response with a cross-reaction against different epitopes or antigens expressed by both melanoma cells and normal melanocytes (e.g. MART-1, GP100, TRP1-2, tyrosinase) [2, 3].\n\nThe overall incidence of newly developed vitiligo with PD-1 inhibitors varies between 8 and 25% [2]. The relative risk of all-grade vitiligo with anti-PD-1 and anti-CTLA-4 (meta-analysis) is 16.3% [4]. Vitiligoid lesions, however, occur more frequently with anti-PD-1 agents than with other immunotherapies (overall incidence of 3.4%) previously used in melanoma, including anti-CTLA-4 [5].\n\nVitiligo has not been described to date in other types of solid cancers treated with PD-1/PD-L1 antibodies [6], but a potential underestimation because of a lack of systematic examination of the entire skin surface cannot be ruled out.\n\nVitiligo usually develops after several months of treatment and does not appear to be dose related [7]. It can be preceded by erythematous inflammatory lesions and may appear to look like Pityriasis rosea [2]. Lesions are mainly generalized and bilateral, but focal or segmental presentations can also be seen as vitiligoid lesions localized around skin metastases [7]. Associated hair repigmentation or depigmentation can be also observed [8].\n\nIn pooled analysis, patients who presented with vitiligo during immunotherapy were found to have a higher frequency and severity of irAEs than those without vitiligo [2, 9]. Although vitiligo can precede the radiologic objective responses, the occurrence of vitiligo cannot be considered an early sign of response to immunotherapy. This perhaps could be an important indicator of antimelanoma immunity and associated improved survival. Whether this relates to solid cancers as well we are not sure [3]. It has been hypothesized that PD-1 inhibitors induce vitiligo-like depigmentation in melanoma patients via the antimelanoma immune response, which may also target healthy melanocytes owing to overlapping antigen expression [10].\n\nPD-1 inhibitors are associated with a variety of cutaneous irAEs, including pruritus, maculopapular eruptions, eczema, lichenoid dermatoses, psoriasiform eruptions, vitiligo, sarcoidosis and severe reactions such as Stevens–Johnson syndrome/toxic epidermal necrolysis [9].\n\nThe pathogenesis perhaps involves an aberrant targeting of antigens into the dermis/epidermis by reactivated CD4+/CD8+ T cells, generate an inflammatory process after cross-reaction with normal skin. However, the specific self-antigens driving T-cell infiltration into the skin have not been identified [7]. Vitiligo can be observed in other tumor types beyond melanoma when receiving immunotherapy and may be a sign of potent immune activation.\n\nACKNOWLEDGEMENTS\nCloyce Stetson (Slides), Brent Paulger (diagnostic biopsy).\n\nConsent\nConsent was obtained.\n\nCONFLICT OF INTEREST STATEMENT\nDr Bulbul has served advisory boards for AstraZeneca and Pfizer.\n==== Refs\nREFERENCES\n1 \nHwang SJE , Carlos G , Wakade D , Byth K , Kong BY , Chou S , et al \nCutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: a single-institution cohort . J Am Acad Dermatol 2016 ;74 :455 –461.e1 .26793994 \n2 \nHua C , Boussemart L , Mateus C , Routier E , Boutros C , Cazenave H , et al \nAssociation of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab . JAMA Dermatol 2016 ;152 :45 –51 .26501224 \n3 \nLo JA , Fisher DE , Flaherty KT \nPrognostic significance of cutaneous adverse events associated with pembrolizumab therapy . JAMA Oncol 2015 ;1 :1340 –1 .26270186 \n4 \nAbdel-Rahman O , ElHalawani H , Fouad M \nRisk of cutaneous toxicities in patients with solid tumors treated with immune checkpoint inhibitors: a meta-analysis . Future Oncol 2015 ;11 :2471 –84 .26274495 \n5 \nRobert C , Long GV , Brady B , Dutriaux C , Maio M , Mortier L , et al \nNivolumab in previously untreated melanoma without BRAF mutation . N Engl J Med 2015 ;372 :320 –30 .25399552 \n6 \nMcDermott DF , Sosman JA , Sznol M , Massard C , Gordon MS , Hamid O , et al \nAtezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study . J Clin Oncol 2016 ;34 :833 –42 .26755520 \n7 \nSibaud V , Meyer N , Lamant L , Vigarios E , Mazieres J , Delord JP \nDermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies . Curr Opin Oncol 2016 ;28 :254 –63 .27136138 \n8 \nHofmann L , Forschner A , Loquai C , Goldinger SM , Zimmer L , Ugurel S , et al \nCutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy . Eur J Cancer 2016 ;60 :190 –209 .27085692 \n9 \nNakamura Y , Tanaka R , Asami Y , Teramoto Y , Imamura T , Sato S , et al \nCorrelation between vitiligo occurrence and clinical benefit in advanced melanoma patients treated with nivolumab: a multi-institutional retrospective study . J Dermatol 2017 ;44 :117 –22 .27510892 \n10 \nHoughton AN , Eisinger M , Albino AP , Cairncross JG , Old LJ \nSurface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets . J Exp Med 1982 ;156 :1755 –66 .7175440\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "2053-8855", "issue": "2019(3)", "journal": "Oxford medical case reports", "keywords": "Vitiligo; hypopigmentation; irAE; pembrolizumab", "medline_ta": "Oxf Med Case Reports", "mesh_terms": null, "nlm_unique_id": "101642070", "other_id": null, "pages": "omz016", "pmc": null, "pmid": "30949354", "pubdate": "2019-03", "publication_types": "D002363:Case Reports", "references": "25399552;26270186;26274495;26501224;26755520;26793994;27085692;27136138;27510892;7175440", "title": "Vitiligoid hypopigmentation associated with pembrolizumab in metastatic head and neck cancer.", "title_normalized": "vitiligoid hypopigmentation associated with pembrolizumab in metastatic head and neck cancer" }

[ { "companynumb": "US-009507513-2005USA008122", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PEMBROLIZUMAB" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "125514", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "POWDER FOR INJECTION", "drugdosagetext": "UNK", "drugenddate": "201802", "drugenddateformat": "610", "drugindication": "HEAD AND NECK CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201702", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "KEYTRUDA" } ], "patientagegroup": null, "patientonsetage": "32", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Vitiligo", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Immune-mediated hypothyroidism", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 201807" } }, "primarysource": { "literaturereference": "BULBUL A. VITILIGOID HYPOPIGMENTATION ASSOCIATED WITH PEMBROLIZUMAB IN METASTATIC HEAD AND NECK CANCER. OXFORD MEDICAL CASE REPORTS. 2019?3:132-4", "literaturereference_normalized": "vitiligoid hypopigmentation associated with pembrolizumab in metastatic head and neck cancer", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200529", "receivedate": "20200529", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17840284, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" }, { "companynumb": "NVSC2020US173057", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DOCETAXEL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "201525", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "TONSIL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOCETAXEL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "TONSIL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "5 FLUOROURACIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "76959", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "TONSIL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." } ], "patientagegroup": null, "patientonsetage": "32", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Tonsil cancer metastatic", "reactionmeddraversionpt": "23.0", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 201701" } }, "primarysource": { "literaturereference": "BULBUL A. VITILIGOID HYPOPIGMENTATION ASSOCIATED WITH PEMBROLIZUMAB IN METASTATIC HEAD AND NECK CANCER. OXFORD MEDICAL CASE REPORTS. 2019?3:132-4", "literaturereference_normalized": "vitiligoid hypopigmentation associated with pembrolizumab in metastatic head and neck cancer", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200620", "receivedate": "20200620", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17920376, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200714" } ]

{ "abstract": "Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome, is a serious, sometimes lethal, immunological reaction to drug metabolites involving multiple organ systems. Some of the common causative agents of DRESS include allopurinol, minocycline, sulfasalazine, azathioprine, antiepileptic drugs, and hydroxychloroquine. DRESS is often misdiagnosed and challenging to clinically manage due to the disease's myriad presentations, acute complications, and long-term sequela after initial resolution. We present the case of a 39-year-old female patient that developed type 1 diabetes as a sequela of DRESS. The patient originally presented to the emergency department with three days of fevers and a pruritic erythematous maculopapular rash that began two weeks prior. She had recently started an antibiotic course and had also been on a long-term antiepileptic drug regimen. Following a thorough clinical examination, the patient was diagnosed with DRESS and treated accordingly. Over the next four months, she went on to have multiple hospitalizations with several admissions to the medical intensive care unit. She had numerous complications including significant facial edema, seizures, bacterial pneumonia, sepsis, hypovolemic shock, acute respiratory distress syndrome, diabetic ketoacidosis, nonalcoholic steatohepatitis, liver failure, and recurring DRESS rashes despite treatment with high-dose intravenous steroids and immunosuppressants. During this time, the patient developed a rare form of uncontrolled type 1 diabetes mellitus not explained by autoantibody production or continued high-dose steroid use. Fulminant type 1 diabetes mellitus is a sequela of DRESS that is poorly understood and rarely reported. When it occurs, it significantly and negatively affects patient prognosis and requires careful monitoring to assure proper glycemic control.", "affiliations": "School of Medicine, Renaissance School of Medicine at Stony Brook University, 101 Nicolls Road, Health Sciences Center, Level 4, Stony Brook, NY 11794, USA.;Department of Internal Medicine, Endocrinology & Metabolism, Renaissance School of Medicine at Stony Brook University, 101 Nicolls Road, Health Sciences Center, Level 4, Stony Brook, NY 11794, USA.;Departments of Dermatology and Pathology, Renaissance School of Medicine at Stony Brook University, 101 Nicolls Road, Health Sciences Center, Level 4, Stony Brook, NY 11794, USA.;Department of Internal Medicine, Endocrinology & Metabolism, Renaissance School of Medicine at Stony Brook University, 101 Nicolls Road, Health Sciences Center, Level 4, Stony Brook, NY 11794, USA.;Department of Internal Medicine, Endocrinology & Metabolism, Renaissance School of Medicine at Stony Brook University, 101 Nicolls Road, Health Sciences Center, Level 4, Stony Brook, NY 11794, USA.", "authors": "Perez|Pedro|P|https://orcid.org/0000-0002-6987-0157;Sze|Wilson|W|;Lozeau|Daniel|D|;Avichal|Dipa|D|;Miller|Joshua|J|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1155/2020/9018147", "fulltext": "\n==== Front\nCase Rep Endocrinol\nCase Rep Endocrinol\nCRIE\nCase Reports in Endocrinology\n2090-6501 2090-651X Hindawi \n\n10.1155/2020/9018147\nCase Report\nDevelopment of Fulminant Type 1 Diabetes Mellitus in a Patient with DRESS Syndrome\nhttps://orcid.org/0000-0002-6987-0157Perez Pedro pedro.perez@stonybrookmedicine.edu\n1\n Sze Wilson \n2\n Lozeau Daniel \n3\n Avichal Dipa \n2\n Miller Joshua \n2\n \n1School of Medicine, Renaissance School of Medicine at Stony Brook University, 101 Nicolls Road, Health Sciences Center, Level 4, Stony Brook, NY 11794, USA\n\n2Department of Internal Medicine, Endocrinology & Metabolism, Renaissance School of Medicine at Stony Brook University, 101 Nicolls Road, Health Sciences Center, Level 4, Stony Brook, NY 11794, USA\n\n3Departments of Dermatology and Pathology, Renaissance School of Medicine at Stony Brook University, 101 Nicolls Road, Health Sciences Center, Level 4, Stony Brook, NY 11794, USA\nAcademic Editor: Osamu Isozaki\n\n\n2020 \n30 8 2020 \n2020 901814718 3 2020 13 8 2020 21 8 2020 Copyright © 2020 Pedro Perez et al.2020This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome, is a serious, sometimes lethal, immunological reaction to drug metabolites involving multiple organ systems. Some of the common causative agents of DRESS include allopurinol, minocycline, sulfasalazine, azathioprine, antiepileptic drugs, and hydroxychloroquine. DRESS is often misdiagnosed and challenging to clinically manage due to the disease's myriad presentations, acute complications, and long-term sequela after initial resolution. We present the case of a 39-year-old female patient that developed type 1 diabetes as a sequela of DRESS. The patient originally presented to the emergency department with three days of fevers and a pruritic erythematous maculopapular rash that began two weeks prior. She had recently started an antibiotic course and had also been on a long-term antiepileptic drug regimen. Following a thorough clinical examination, the patient was diagnosed with DRESS and treated accordingly. Over the next four months, she went on to have multiple hospitalizations with several admissions to the medical intensive care unit. She had numerous complications including significant facial edema, seizures, bacterial pneumonia, sepsis, hypovolemic shock, acute respiratory distress syndrome, diabetic ketoacidosis, nonalcoholic steatohepatitis, liver failure, and recurring DRESS rashes despite treatment with high-dose intravenous steroids and immunosuppressants. During this time, the patient developed a rare form of uncontrolled type 1 diabetes mellitus not explained by autoantibody production or continued high-dose steroid use. Fulminant type 1 diabetes mellitus is a sequela of DRESS that is poorly understood and rarely reported. When it occurs, it significantly and negatively affects patient prognosis and requires careful monitoring to assure proper glycemic control.\n==== Body\n1. Introduction\nDrug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome (DIHS), is a serious, sometimes lethal, immunological reaction to drug metabolites involving multiple organ systems [1]. DRESS falls within a spectrum of skin and mucous membrane drug reactions termed severe cutaneous adverse reactions (SCARs), which contains other pathologies such as Steven–Johnson syndrome and acute generalized exanthematous pustulosis (AGEP). DRESS is typically characterized by fevers, facial edema, erupting skin rash, eosinophilia, atypical lymphocytosis, and lymphadenopathy [2]. The liver is often the primary visceral organ affected; however, other organs, such as the spleen, can also be involved [3]. There are reported autoimmune sequelae of DRESS such as systemic lupus erythematosus, thyroiditis, and diabetes mellitus (DM) [4–7]. Diagnosis of these sequelae is often delayed due to the variable nature of DRESS presentation. Having a clearer understanding of the clinical facets of DRESS will be beneficial in providing rapid identification and treatment, while consequently improving outcomes. In this case report, we present a patient with DRESS that developed a rare form of uncontrolled type 1 DM not explained by autoantibody production or continued high-dose steroid use.\n\n2. Case Presentation\nA 39-year-old African American female with a medical history of chronic focal epilepsy presented to Stony Brook University Hospital emergency department with three days of fevers (>38°C) and mildly pruritic erythematous maculopapular rash. The rash began two weeks prior in the left arm and gradually spread bilaterally to the trunk, face, oropharynx, periocular space, and legs (Figure 1). As there was initial suspicion for a drug-related rash, the patient's medication history was reviewed. She had been recently started on an antibiotic course of amoxicillin by her primary doctor for unilateral neck lymphadenopathy and exudative pharyngitis. Additionally, she had been on a long-term carbamazepine therapy for epilepsy. One year ago, the patient's antiepileptic medication regimen was changed as she wanted to become pregnant. She had been slowly tapering off carbamazepine and was started on lamotrigine. At the time of presentation, she was taking both carbamazepine and lamotrigine.\n\nThe patient's initial laboratory studies showed an elevated neutrophil count (10.47 K/ul), mild eosinophilia (6–8%), and transaminitis (AST : 48 IU/L; ALT : 42 IU/L). Initial evaluation by the dermatology service suggested a differential diagnosis of AGEP secondary to amoxicillin versus DIHS secondary to lamotrigine or carbamazepine use. A computed tomography (CT) scan revealed no clear etiology of infection, blood cultures were negative, skin cultures from pustules only grew normal skin flora, and skin biopsy revealed nonspecific findings most consistent with AGEP (Figure 2). CT abdominal scan showed multiple wedge-shaped lesions within the spleen suspicious for focal areas of infarction and ischemia. This discovery in conjunction with the rest of the patient's presentation yielded a diagnosis of DRESS [8]. Over the next four months, this patient would have multiple hospitalizations with several admissions to the medical intensive care unit (MICU). The patient had numerous complications including significant facial edema, seizures, bacterial pneumonia, sepsis, hypovolemic shock, acute respiratory distress syndrome (ARDS) requiring intubation, diabetic ketoacidosis (DKA), nonalcoholic steatohepatitis, liver failure requiring transfer to a liver transplant center (transplant was ultimately not needed), and recurring DRESS rashes despite treatment with high-dose intravenous steroids and immunosuppressants (e.g., cyclosporine). Of interest to this case report, the patient developed persistently uncontrolled hyperglycemia complicated by DKA in the setting of sepsis.\n\nApproximately, a month following onset of the rash, the patient's serum glucose was found to be over 500 mg/dL with a hemoglobin A1C of 7.1% without a prior history of diabetes mellitus (DM). The patient was started on insulin therapy for probable steroid-induced diabetes mellitus (SIDM), as she was requiring a high-dose steroid regimen for DRESS. The patient's SIDM was complicated by DKA during a sepsis episode precipitated by a bacterial pneumonia. She remained in the MICU for several weeks where she was managed with respiratory support, antibiotics, insulin, and steroids. She was eventually discharged from the hospital following improvement of her respiratory status, sepsis, liver failure, DRESS rash, and serum glucose levels. The steroids were tapered off during outpatient follow-up, and her SIDM briefly improved. However, despite continuing a steroid taper, she had significant fluctuating fasting glucose levels and her insulin regimen was titrated. The patient continued to have persistently elevated serum glucose levels (>300 mg/dL) requiring insulin therapy despite cessation of steroids. She required multiple daily insulin injections and wore a continuous glucose monitoring device (CGM). Glutamic acid decarboxylase (GAD) antibodies and islet cell cytoplasmic autoantibodies (ICAs) were tested for correlation with autoimmune subtype of type 1 DM; however, they were found to be negative. The patient's new onset uncontrolled type 1 DM was originally diagnosed as SIDM, which normally improves following reduction or cessation of steroids. However, given her worsening glycemic control in the context of tapering and short-term cessation of steroids, the patient was diagnosed as having a rare but previously documented type of fulminant type 1 DM as a sequela of DRESS [4].\n\n3. Discussion\nDRESS syndrome is a clinically significant skin phenomenon with systemic involvement within the SCARs phylogeny of cutaneous immune responses to drug exposure. DRESS can be lethal with a mortality rate approaching 10% and is believed to occur with an incidence ranging from 1 : 1000 to 1 : 10,000 drug exposure, although exact incidence is unknown and may vary by population [2–4]. DRESS, which is ultimately a clinical diagnosis, can often be misdiagnosed as well as mismanaged due to its varying presentations, unique and difficult manifestations, and hosts of sequelae. The patient presented here developed fulminant type I DM as a sequela of DRESS and required increasing doses of insulin and a CGM device. If this patient's DM continues to progress, they may require an insulin pump, thus highlighting the serious nature of this DRESS sequela.\n\nThe patient's early presentation was classic of DRESS syndrome, with lymphadenopathy, facial edema, erupting morbilliform rash, fevers, and liver and spleen involvement. It is worth noting that she initially had mild transaminitis, which quickly progressed to significant transaminitis and near liver failure; thus, the original liver enzyme values are not necessarily prognostic of disease progression. Nevertheless, liver involvement is highly correlated with DRESS and found to occur as high as 87% of DRESS patients [3]. Moreover, this patient had splenic infarcts, a finding previously appreciated in the literature in DRESS patients [8]. There are multiple published criteria that are used for diagnosing DRESS. Among these, RegiSCAR and particularly Bocquet's criteria have been found to be diagnostically superior [9]. The seven characteristics (three of seven characteristics must be met) of the RegiSCAR criteria are skin eruption, fever (>38°C), lymphadenopathy at two or more sites, involvement of one internal organ, lymphocytosis or lymphopenia, blood eosinophilia (>10% or 700/µL), and thrombocytopenia (<120 × 103/µL). Alternatively, simpler Bocquet's criteria require skin eruption, blood eosinophilia (>1.5 × 103/µL), and internal organ involvement. Under these guidelines, this patient definitively meets four of the seven RegiSCAR characteristics and closely approaches one of the remaining three (mild eosinophilia below criteria threshold). Likewise, the patient meets two of the three characteristics of Bocquet's criteria with eosinophil levels below the suggested threshold. The patient's eosinophil levels were not closely monitored after admission, thus raising the possibility that the levels may have increased later during disease progression.\n\nIt is not fully clear what agent induced DRESS syndrome in this case presentation. The patient had been on long-term carbamazepine treatment for epilepsy, had begun lamotrigine a few months prior, and just initiated a course of amoxicillin. β-lactams are more frequently associated with AGEP; however, they are also known to cause DRESS flare-ups in patients with DRESS induced by a different drug type [10, 11]. Anticonvulsants are well-recognized for inducing DRESS, particularly lamotrigine and carbamazepine [2, 3]. However, this patient had been on carbamazepine for over ten years and had been tapering it over the last year. This makes carbamazepine an unlikely trigger of DRESS in this scenario. The patient's DRESS rash had been ongoing for about two weeks before presentation. She began taking amoxicillin a few days before needing to come to the hospital. As DRESS normally takes 2–12 weeks to develop after drug exposure, it seems plausible that lamotrigine may have originated the DRESS syndrome, and this was exacerbated by amoxicillin use.\n\nThe patient's hyperglycemia was first noted in outpatient setting about a month following the original DRESS rash. As the patient had been on an intensive steroid and immunosuppressant treatment regimen for DRESS, the globally elevated hyperglycemia was believed to be SIDM. SIDM is an expected outcome of long-term medical glucocorticoid use. The prognosis for SIDM is generally positive; once the steroid dosing is reduced, insulin requirements decrease, and normal endocrine function is reestablished [12]. While in the hospital, the patient continued to receive insulin to control her serum glucose level. However, once the DRESS syndrome improved and she was tapered from steroids, her serum glucose levels paradoxically continued to increase. This persisted for months and required close endocrinology outpatient follow-up. Past studies have reported thyroiditis, systemic lupus erythematosus, autoimmune hemolytic anemia, vitiligo, alopecia, and type 1 DM as autoimmune sequelae of DRESS [5, 6, 13, 14]. Previously reported case reports of type 1 DM as sequela of DRESS were characterized by sudden onset typically between 2 weeks−10 months post-DRESS, lack of GAD or ICA antibodies, low or absent C-peptide levels, and significant death of pancreatic β-cells. However, there has also been at least one report of GAD-positive post-DRESS type 1 DM [7]. The rapid onset and lack of pancreatic autoantibodies are more consistent with this patient's presentation; this subtype has been previously termed nonautoimmune fulminant type 1 DM.\n\nNonautoimmune fulminant type 1 DM as a development from DRESS is uncommon and has been scarcely reported. A previous study by Chen et al. found 1 in 43 patients with fulminant type 1 DM 1-2 months post-DRESS [6]. A similar study by Kano et al. observed 5 in 145 patients having type 1 DM in a similar time frame after DRESS resolution [13]. Finally, Chiou et al. reported 2 in 30 patients with type 1 DM post-DRESS [15]. Interestingly, it was previously found that the MHC I serotype, HLA-B62, was found in a greater frequency in fulminant type 1 DM associated with DRESS syndrome [16]. In a follow-up study, we would like to test the MHC serotype present in this patient. The mechanisms underlying the development of fulminant type 1 DM as a sequela of DRESS are complicated and not well understood. There seems to be an association with reactivation of herpes virus HHV-6, as well as a loss of suppressive function by T-regulatory cells, a type of immunosuppressant T-cell.\n\nFulminant type 1 DM as a sequela of DRESS is a poorly understood and rarely reported clinical phenomenon. When it occurs, it significantly and negatively affects the prognosis and requires a constant, careful, and financially costly management of these patients to assure proper glycemic control. Earlier identification of this chronic complication of DRESS will aid clinicians in more efficient treatment that will improve patient outcomes. Clearly, more work is needed to further elucidate the physiology underlying this unique pathology.\n\nConflicts of Interest\nThe authors declare that they have no conflicts of interest.\n\nFigure 1 Patient's forearms four weeks following the original erupting rash. Pictured here are follicular erythematous papules with scattered postinflammatory hyperpigmented macules becoming confluent in areas with desquamation. This pattern persisted bilaterally in the trunk and upper and lower extremities.\n\nFigure 2 Low-power microscopy images of the patient's skin biopsy (40x and 100x) show interface dermatitis with focal spongiotic dermatitis. On the high-power image, (400x) there is vacuolar interface dermatitis (lymphocytes tagging along the dermoepidermal junction) and rare necrotic keratinocytes within the epidermis. The histopathologic changes are nonspecific but can be observed in drug eruption reactions.\n==== Refs\n1 Cho Y. T. Yang C. W. Chu C. Y. Drug reaction with eosinophilia and systemic symptoms (DRESS): an interplay among drugs, viruses, and immune system International Journal of Molecular Sciences 2017 18 10.3390/ijms18061243 2-s2.0-85020775600 \n2 Husain Z. Reddy B. Y. Schwartz R. A. DRESS syndrome: Part I. clinical perspectives Journal of the American Academy of Dermatology 2013 68 693 e1 14 10.1016/j.jaad.2013.01.033 2-s2.0-84876383583 23602182 \n3 Lin I.-C. Yang H.-C. Strong C. Liver injury in patients with DRESS: a clinical study of 72 cases Journal of the American Academy of Dermatology 2015 72 6 984 991 10.1016/j.jaad.2015.02.1130 2-s2.0-84929654524 25801338 \n4 Kano Y. Ishida T. Hirahara K. Shiohara T. Visceral involvements and long-term sequelae in drug-induced hypersensitivity syndrome Medical Clinics of North America 2010 94 4 743 759 10.1016/j.mcna.2010.03.004 2-s2.0-77953597045 20609861 \n5 Aota N. Hirahara K. Kano Y. Fukuoka T. Yamada A. Shiohara T. Systemic lupus erythematosus presenting with Kikuchi-Fujimoto’s disease as a long-term sequela of drug-induced hypersensitivity syndrome Dermatology 2009 218 3 275 277 10.1159/000187619 2-s2.0-62049085338 19088463 \n6 Chen Y.-C. Chang C.-Y. Cho Y.-T. Chiu H.-C. Chu C.-Y. Long-term sequelae of drug reaction with eosinophilia and systemic symptoms: a retrospective cohort study from Taiwan Journal of the American Academy of Dermatology 2013 68 3 459 465 10.1016/j.jaad.2012.08.009 2-s2.0-84873704492 22959230 \n7 Chiang A. Shiu J. Elsensohn A. N. Chapman L. W. De Feraudy S. Smith J. Classic autoimmune type 1 diabetes mellitus after a case of drug reaction with eosinophilia and systemic symptoms (DRESS) JAAD Case Reports 2018 4 4 295 297 10.1016/j.jdcr.2017.10.003 2-s2.0-85044591054 29693052 \n8 LaHood N. Sokol K. DRESS syndrome associated with splenic thrombosis Annals of Allergy, Asthma & Immunology 2017 119 5 463 464 10.1016/j.anai.2017.08.288 2-s2.0-85038226375 \n9 Kim D.-H. Koh Y.-I. Comparison of diagnostic criteria and determination of prognostic factors for drug reaction with eosinophilia and systemic symptoms syndrome Allergy, Asthma & Immunology Research 2014 6 3 216 221 10.4168/aair.2014.6.3.216 2-s2.0-84899640400 \n10 Mardivirin L. Valeyrie-Allanore L. Branlant-Redon E. Amoxicillin-induced flare in patients with DRESS (Drug reaction with eosinophilia and systemic symptoms): report of seven cases and demonstration of a direct effect of amoxicillin on human herpesvirus 6 replication in vitro European Journal of Dermatology 2010 20 1 068 073 10.1684/ejd.2010.0821 2-s2.0-76749119336 \n11 De A. Das S. Sarda A. Pal D. Biswas P. Acute generalised exanthematous pustulosis: an update Indian Journal of Dermatology 2018 63 1 22 29 10.4103/ijd.ijd_581_17 2-s2.0-85042259205 29527022 \n12 Tamez-Pérez H. E. Quintanilla-Flores D. L. Rodriguez-Gutierrez R. Gonzalez-Gonzalez J. G. Tamez-Pena A. L. Steroid hyperglycemia: prevalence, early detection and therapeutic recommendations: a narrative review World Journal of Diabetes 2015 6 8 1073 1081 10.4239/wjd.v6.i8.1073 26240704 \n13 Kano Y. Tohyama M. Aihara M. Sequelae in 145 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms: survey conducted by the Asian research committee on severe cutaneous adverse reactions (ASCAR) The Journal of Dermatology 2015 42 3 276 282 10.1111/1346-8138.12770 2-s2.0-84924140432 25623158 \n14 Iskandarli M. Ozturk G. Alopecia areata and vitiligo as a long-term sequelae of drug reaction with eosinophilia and systemic symptoms syndrome Indian Journal of Dermatology 2016 61 2 p. 238 10.4103/0019-5154.177781 2-s2.0-84961125753 \n15 Chiou C.-C. Yang L.-C. Hung S.-I. Clinicopathlogical features and prognosis of drug rash with eosinophilia and systemic symptoms: a study of 30 cases in Taiwan Journal of the European Academy of Dermatology and Venereology 2008 22 9 1044 1049 10.1111/j.1468-3083.2008.02585.x 2-s2.0-49649122483 18627428 \n16 Onuma H. Tohyama M. Imagawa A. High frequency of HLA B62 in fulminant type 1 diabetes with the drug-induced hypersensitivity syndrome The Journal of Clinical Endocrinology & Metabolism 2012 97 12 E2277 E2281 10.1210/jc.2012-2054 2-s2.0-84870755128 23071161\n\n", "fulltext_license": "CC BY", "issn_linking": "2090-651X", "issue": "2020()", "journal": "Case reports in endocrinology", "keywords": null, "medline_ta": "Case Rep Endocrinol", "mesh_terms": null, "nlm_unique_id": "101576457", "other_id": null, "pages": "9018147", "pmc": null, "pmid": "32908723", "pubdate": "2020", "publication_types": "D002363:Case Reports", "references": "27057057;24843796;26240704;20609861;18627428;25623158;23602182;29150073;19822481;28598363;29693052;29527022;22959230;23071161;19088463;25801338", "title": "Development of Fulminant Type 1 Diabetes Mellitus in a Patient with DRESS Syndrome.", "title_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome" }

[ { "companynumb": "US-ALEMBIC PHARMACUETICALS LIMITED-2020SCAL000491", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "090607", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PARTIAL SEIZURES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PHARYNGITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHADENOPATHY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "090607", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SLOWLY TAPERING OFF CARBAMAZEPINE", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fulminant type 1 diabetes mellitus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hyperglycaemia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Transaminases increased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Pneumonia bacterial", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Face oedema", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Non-alcoholic steatohepatitis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Blood glucose increased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Lymphadenopathy", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Rash maculo-papular", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Rash pruritic", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Acute respiratory distress syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Splenic infarction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Rash erythematous", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Glycosylated haemoglobin increased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Rash", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hypovolaemic shock", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Diabetes mellitus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Seizure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Rash morbilliform", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "PEREZ P, SZE W, LOZEAU D, AVICHAL D, MILLER J. DEVELOPMENT OF FULMINANT TYPE 1 DIABETES MELLITUS IN A PATIENT WITH DRESS SYNDROME. CASE REPORTS IN ENDOCRINOLOGY. 2020", "literaturereference_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201118", "receivedate": "20201118", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18513264, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" }, { "companynumb": "US-UNICHEM PHARMACEUTICALS (USA) INC-UCM202010-001196", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHADENOPATHY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PHARYNGITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PARTIAL SEIZURES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "090170", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PARTIAL SEIZURES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." } ], "patientagegroup": "5", "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Rash", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Fulminant type 1 diabetes mellitus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "3" }, { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Acute respiratory distress syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypovolaemic shock", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Face oedema", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Non-alcoholic steatohepatitis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Seizure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pneumonia bacterial", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PEREZ P, SZE W, LOZEAU D, AVICHAL D, MILLER J. DEVELOPMENT OF FULMINANT TYPE 1 DIABETES MELLITUS IN A PATIENT WITH DRESS SYNDROME. CASE REP ENDOCRINOL. 2020?2020:1-5. DOI:10.1155/2020/9018147", "literaturereference_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20201019", "receivedate": "20201019", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18403364, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210114" }, { "companynumb": "US-DRREDDYS-USA/USA/20/0127904", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PHARYNGITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "076708", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE TABLETS" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DOSE TAPERED", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHADENOPATHY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." } ], "patientagegroup": "5", "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Fulminant type 1 diabetes mellitus", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Splenic infarction", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Non-alcoholic steatohepatitis", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Acute respiratory distress syndrome", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Seizure", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pneumonia bacterial", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Transaminases increased", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hypovolaemic shock", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "PEREZ P, SZE W, LOZEAU D, AVICHAL D, MILLER J. DEVELOPMENT OF FULMINANT TYPE 1 DIABETES MELLITUS IN A PATIENT WITH DRESS SYNDROME. CASE REPORTS IN ENDOCRINOLOGY. 2020?ARTICLE NUMBER 9018147. DOI:10.1155/2020/9018147.", "literaturereference_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210726", "receivedate": "20201014", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18381824, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "US-TARO-2020TAR01588", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "074649", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." } ], "patientagegroup": null, "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Face oedema", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hypovolaemic shock", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute respiratory distress syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Seizure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Steatohepatitis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Pneumonia bacterial", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "PEREZ P, SZE W, LOZEAU D, AVICHAL D, MILLER J. DEVELOPMENT OF FULMINANT TYPE 1 DIABETES MELLITUS IN A PATIENT WITH DRESS SYNDROME. CASE REP ENDOCRINOL. 2020?2020:ARTICLE ID: 9018147? 1-5", "literaturereference_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201019", "receivedate": "20201019", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18398986, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" }, { "companynumb": "US-TEVA-2020-US-1842098", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "61926", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PHARYNGITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "61926", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHADENOPATHY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "76420", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PARTIAL SEIZURES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SLOW TAPERING OFF", "drugenddate": null, "drugenddateformat": null, "drugindication": "PARTIAL SEIZURES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." } ], "patientagegroup": "5", "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Seizure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Acute respiratory distress syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hypovolaemic shock", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fulminant type 1 diabetes mellitus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "3" }, { "reactionmeddrapt": "Splenic infarction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pneumonia bacterial", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Non-alcoholic steatohepatitis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PEREZ P, SZE W, LOZEAU D, AVICHAL D, MILLER J. DEVELOPMENT OF FULMINANT TYPE 1 DIABETES MELLITUS IN A PATIENT WITH DRESS SYNDROME. CASE-REP-ENDOCRINOL 2020?2020:9018147.", "literaturereference_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201112", "receivedate": "20201029", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18443046, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210114" }, { "companynumb": "US-GLENMARK PHARMACEUTICALS-2020GMK049996", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DOSE TAPERED (OVER LAST ONE YEAR -BEFORE REPORT)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PHARYNGITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHADENOPATHY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "079099", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK (TAKING OVER 10 YEARS - BEFORE REPORT)", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." } ], "patientagegroup": null, "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute respiratory distress syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hypovolaemic shock", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Non-alcoholic steatohepatitis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Transaminases increased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Fulminant type 1 diabetes mellitus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Splenic infarction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Seizure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pneumonia bacterial", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "PEREZ P, SZE W, LOZEAU D, AVICHAL D, MILLER J. DEVELOPMENT OF FULMINANT TYPE 1 DIABETES MELLITUS IN A PATIENT WITH DRESS SYNDROME.. CASE REPORTS IN ENDOCRINOLOGY. 2020", "literaturereference_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201019", "receivedate": "20201019", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18398929, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20210114" }, { "companynumb": "US-MYLANLABS-2020M1087085", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PARTIAL SEIZURES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHADENOPATHY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PHARYNGITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "076630", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PARTIAL SEIZURES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "SLOW TAPERING OFF", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." } ], "patientagegroup": null, "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Fulminant type 1 diabetes mellitus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "3" }, { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Seizure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute respiratory distress syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hypovolaemic shock", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Splenic infarction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Pneumonia bacterial", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Non-alcoholic steatohepatitis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PEREZ P, SZE W, LOZEAU D, AVICHAL D, MILLER J. DEVELOPMENT OF FULMINANT TYPE 1 DIABETES MELLITUS IN A PATIENT WITH DRESS SYNDROME. CASE-REP-ENDOCRINOL 2020?2020:9018147.", "literaturereference_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201016", "receivedate": "20201016", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18392332, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210114" }, { "companynumb": "NVSC2020US275885", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "64076", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHADENOPATHY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "016608", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "LONG-TERM, TAPERING OFF", "drugenddate": null, "drugenddateformat": null, "drugindication": "PARTIAL SEIZURES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PARTIAL SEIZURES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "64076", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PHARYNGITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." } ], "patientagegroup": null, "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PEREZ P, SZE W, LOZEAU D, AVICHAL D, MILLER J. DEVELOPMENT OF FULMINANT TYPE 1 DIABETES MELLITUS IN A PATIENT WITH DRESS SYNDROME. CASE REPORTS IN ENDOCRINOLOGY. 2020?2020:1-5", "literaturereference_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20201015", "receivedate": "20201015", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18389985, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" }, { "companynumb": "US-GLAXOSMITHKLINE-US2020GSK186135", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHADENOPATHY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PHARYNGITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "020241", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." } ], "patientagegroup": null, "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Rash maculo-papular", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hyperglycaemia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pneumonia bacterial", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute respiratory distress syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Blood glucose increased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Rash erythematous", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Eosinophilia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypovolaemic shock", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute generalised exanthematous pustulosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Non-alcoholic steatohepatitis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Condition aggravated", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fulminant type 1 diabetes mellitus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Neutrophil count increased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Splenic lesion", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Lymphadenopathy", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Rash morbilliform", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Glycosylated haemoglobin increased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Rash pruritic", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Face oedema", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Transaminases increased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PEREZ P, SZE W, LOZEAU D, AVICHAL D, MILLER J. DEVELOPMENT OF FULMINANT TYPE 1 DIABETES MELLITUS IN A PATIENT WITH DRESS SYNDROME. CASE REPORTS IN ENDOCRINOLOGY. 2020", "literaturereference_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200928", "receivedate": "20200928", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18321623, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "US-HIKMA PHARMACEUTICALS USA INC.-US-H14001-20-52343", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LAMOTRIGINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMOTRIGINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "065322", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "LYMPHADENOPATHY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "AMOXICILLIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "065322", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PHARYNGITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AMOXICILLIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBAMAZEPINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "DOSE TAPERED", "drugenddate": null, "drugenddateformat": null, "drugindication": "EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBAMAZEPINE." } ], "patientagegroup": null, "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pneumonia bacterial", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Sepsis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Acute respiratory distress syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Non-alcoholic steatohepatitis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Seizure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fulminant type 1 diabetes mellitus", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Transaminases increased", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Splenic infarction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug reaction with eosinophilia and systemic symptoms", "reactionmeddraversionpt": "23.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Diabetic ketoacidosis", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypovolaemic shock", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PEREZ P, SZE W, LOZEAU D, AVICHAL D, MILLER J. DEVELOPMENT OF FULMINANT TYPE 1 DIABETES MELLITUS IN A PATIENT WITH DRESS SYNDROME. CASE REPORTS IN ENDOCRINOLOGY. 2020?ARTICLE NUMBER 9018147. DOI:10.1155/2020/9018147.", "literaturereference_normalized": "development of fulminant type 1 diabetes mellitus in a patient with dress syndrome", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20201015", "receivedate": "20201015", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18388293, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20210114" } ]

{ "abstract": "Data on pregnancy outcome in alemtuzumab-treated women are scarce and derived from safety reports of clinical trials. We report on seven women with overall eight pregnancies during treatment with alemtuzumab in a real-world setting. All pregnancies occurred within 9 months after alemtuzumab treatment, and two of them within 4 months despite patients being informed on pregnancy prevention. We found one congenital cytomegalovirus infection, one spontaneous abortion, one elective abortion due to extrauterine pregnancy, and five live births without congenital abnormalities or birth defects.", "affiliations": "Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University Federico II, Naples, Italy. cinziavaleria.russo@unina.it.;Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University Federico II, Naples, Italy.;Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University Federico II, Naples, Italy.;Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University Federico II, Naples, Italy.;Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University Federico II, Naples, Italy.;Department of Neurological Sciences, Reproductive and Odontostomatological Sciences, University Federico II, Naples, Italy.", "authors": "Valeria|Russo Cinzia|RC|;Roberta|Lanzillo|L|;Francesco|Saccà|S|;Marcello|Moccia|M|;Antonio|Carotenuto|C|;Vincenzo|Brescia Morra|BM|", "chemical_list": "D000074323:Alemtuzumab", "country": "Italy", "delete": false, "doi": "10.1007/s10072-020-04975-5", "fulltext": null, "fulltext_license": null, "issn_linking": "1590-1874", "issue": "42(8)", "journal": "Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology", "keywords": "Alemtuzumab; Breastfeeding; Cytomegalovirus; Disease modifying treatment; Multiple sclerosis; Pregnancy", "medline_ta": "Neurol Sci", "mesh_terms": "D000022:Abortion, Spontaneous; D000074323:Alemtuzumab; D005260:Female; D006801:Humans; D009103:Multiple Sclerosis; D011247:Pregnancy; D011256:Pregnancy Outcome", "nlm_unique_id": "100959175", "other_id": null, "pages": "3427-3430", "pmc": null, "pmid": "33860394", "pubdate": "2021-08", "publication_types": "D016428:Journal Article", "references": "7517125;28835403;23122652;22442431;23122650;28835401;29438046", "title": "Pregnancy outcomes in alemtuzumab treated women with multiple sclerosis: a case series.", "title_normalized": "pregnancy outcomes in alemtuzumab treated women with multiple sclerosis a case series" }

[ { "companynumb": "IT-SA-2021SA144981", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "ALEMTUZUMAB" }, "drugadditional": "4", "drugadministrationroute": "064", "drugauthorizationnumb": "103948", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, QCY", "drugenddate": "201601", "drugenddateformat": "610", "drugindication": "Relapsing-remitting multiple sclerosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "201601", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALEMTUZUMAB" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ALEMTUZUMAB" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "103948", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Maternal exposure before pregnancy", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALEMTUZUMAB" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Congenital cytomegalovirus infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Maternal exposure before pregnancy", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Intraventricular haemorrhage neonatal", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Foetal growth restriction", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Microcephaly", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cerebral ventricle dilatation", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cerebral calcification", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cerebral cyst", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypertonia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20160101" } }, "primarysource": { "literaturereference": "Russo CV, Lanzillo R, Carotenuto A, Moccia M, Bresciamorra V, Sacca F.. Pregnancy outcomes in alemtuzumab treated women with multiple sclerosis: A case series.. Ann Neurol.. 2021;90(SUPPL 27):S177-8", "literaturereference_normalized": "pregnancy outcomes in alemtuzumab treated women with multiple sclerosis a case series", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "IT", "receiptdate": "20211106", "receivedate": "20210507", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19228866, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" }, { "companynumb": "IT-SA-2021SA144972", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "ALEMTUZUMAB" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "103948", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Concentrate for solution for infusion", "drugdosagetext": "UNK, QCY", "drugenddate": "201601", "drugenddateformat": "610", "drugindication": "Multiple sclerosis", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "201601", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALEMTUZUMAB" } ], "patientagegroup": "5", "patientonsetage": "37", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cytomegalovirus infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug exposure before pregnancy", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20160101" } }, "primarysource": { "literaturereference": "Russo CV, Lanzillo R, Carotenuto A, Moccia M, Bresciamorra V, Sacca F.. Pregnancy outcomes in alemtuzumab treated women with multiple sclerosis: A case series.. Ann Neurol.. 2021;90(Suppl 27):S177-8", "literaturereference_normalized": "pregnancy outcomes in alemtuzumab treated women with multiple sclerosis a case series", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "IT", "receiptdate": "20211103", "receivedate": "20210507", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19228165, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220304" } ]

{ "abstract": "BACKGROUND\nContinuous interscalene nerve block (CISB) is considered to be the most effective method for postoperative analgesia after shoulder surgery with prolonged severe pain. This study was performed to evaluate the minimum effective background infusion rate and the effective background infusion rate of ropivacaine 0.2% for CISB after arthroscopic rotator cuff repair surgery in 95% of patients.\n\n\nMETHODS\nPatients scheduled for arthroscopic rotator cuff repair surgery under general anesthesia at Peking University Third Hospital were prospectively enrolled from December 2011 to May 2012. Preoperatively, an interscalene catheter (ISC) was placed under the guidance of ultrasound and nerve stimulation in each patient. Consecutively, 30 patients with successful nerve block were included. A continuous infusion of ropivacaine 0.2% with a 5 ml patient-controlled bolus available hourly was started at postoperative anesthesia care unit (PACU) after completion of surgery. The initial background infusion rate was 6 ml/h, which was subsequently varied for each consecutive patient according to the analgesic effects of the previous one. The minimum effective background rate was determined using the Dixon and Massey up-and-down method. The effective background rate in 95% of patients was calculated using isotonic analysis.\n\n\nRESULTS\nThe minimum effective background rate based on the Dixon and Massey up-and-down method was 2.8 ml/h (95% CI, 2.3-3.3 ml/h). The effective background rate in 95% of patients calculated with the isotonic regression analysis was 4.4 ml/h (95% CI, 3.8-6.5 ml/h).\n\n\nCONCLUSIONS\nThe effective background rate for patient-controlled interscalene brachial plexus analgesia after shoulder surgery in 50% and 95% of the patients was 2.8 and 4.4 ml/h, respectively.", "affiliations": "Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.;Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China. Email: liminanesth@aliyun.com.;Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.;Department of Anesthesiology, Peking University Third Hospital, Beijing 100191, China.", "authors": "Wei|Yue|Y|;Li|Min|M|;Rong|Yulan|Y|;Guo|Xiangyang|X|", "chemical_list": "D000577:Amides; D000077212:Ropivacaine", "country": "China", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0366-6999", "issue": "127(23)", "journal": "Chinese medical journal", "keywords": null, "medline_ta": "Chin Med J (Engl)", "mesh_terms": "D000328:Adult; D000368:Aged; D000577:Amides; D016058:Analgesia, Patient-Controlled; D001917:Brachial Plexus; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010149:Pain, Postoperative; D011446:Prospective Studies; D000077212:Ropivacaine; D017006:Rotator Cuff", "nlm_unique_id": "7513795", "other_id": null, "pages": "4119-23", "pmc": null, "pmid": "25430460", "pubdate": "2014", "publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't", "references": null, "title": "Effective background infusion rate of ropivacaine 0.2% for patient-controlled interscalene brachial plexus analgesia after rotator cuff repair surgery.", "title_normalized": "effective background infusion rate of ropivacaine 0 2 for patient controlled interscalene brachial plexus analgesia after rotator cuff repair surgery" }

[ { "companynumb": "CN-BAXTER-2015BAX000748", "fulfillexpeditecriteria": "1", "occurcountry": "CN", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "ROPIVACAINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "CONTINUOUS BASAL INFUSION", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ROPIVACAINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PROPOFOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1-2 MG/KG", "drugenddate": null, "drugenddateformat": null, "drugindication": "GENERAL ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PROPOFOL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "REMIFENTANIL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.1 UG.KG-1 MIN-1 AND ADJUSTED ACCORDING TO HEMODYNAMIC RESPONSES", "drugenddate": null, "drugenddateformat": null, "drugindication": "GENERAL ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "REMIFENTANIL" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ROPIVACAINE" }, "drugadditional": null, "drugadministrationroute": "040", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "AND A LOCKOUT TIME OF 60 MINUTES", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ROPIVACAINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ROCURONIUM BROMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GENERAL ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".6", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ROCURONIUM" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ROPIVACAINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GENERAL ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ROPIVACAINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "SEVOFLURANE" }, "drugadditional": null, "drugadministrationroute": "055", "drugauthorizationnumb": "075895", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INHALATION VAPOUR, LIQUID", "drugdosagetext": "1-2% END TIDAL CONCENTRATION", "drugenddate": null, "drugenddateformat": null, "drugindication": "GENERAL ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "QIFUMEI" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ROPIVACAINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "STARTED IN THE POSTOPERATIVE ANESTHESIA CARE UNIT (PACU)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "012", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ROPIVACAINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DEXTROSE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "5% DEXTROSE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MIDAZOLAM\\MIDAZOLAM HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "MAXINUM DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "GENERAL ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MIDAZOLAM" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "FENTANYL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GENERAL ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "008", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FENTANYL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LIDOCAINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1-2 MG/KG", "drugenddate": null, "drugenddateformat": null, "drugindication": "GENERAL ANAESTHESIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LIDOCAINE." } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Horner^s syndrome", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "MIN L, YUE W, YULAN R, XIANGYANG G. EFFECTIVE BACKGROUND INFUSION RATE OF ROPIVACAINE 0.2% FOR PATIENT-CONTROLLED INTERSCALENE BRACHIAL PLEXUS ANALGESIA AFTER ROTATOR CUFF REPAIR SURGERY. CHINESE MEDICAL JOURNAL. 2014 DEC 01;127(23):4119-4123.", "literaturereference_normalized": "effective background infusion rate of ropivacaine 0 2 for patient controlled interscalene brachial plexus analgesia after rotator cuff repair surgery", "qualification": "3", "reportercountry": "CN" }, "primarysourcecountry": "CN", "receiptdate": "20150113", "receivedate": "20150113", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10708206, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" } ]

{ "abstract": "Psoralen compounds such as methoxsalen are photosensitizer agents used in conjunction with ultraviolet A (UVA) radiation exposure as photochemotherapy (Psoralens and ultraviolet-A therapy [PUVA therapy]) for certain epidermal skin disorders such as psoriasis and vitiligo. Methoxsalen has been shown to be associated with premature cataract formation by forming adducts with lens proteins following oral administration and subsequent UVA exposure. Hence, the use of UV-filtering glasses is recommended during PUVA therapy sessions. Ocular tissues can be exposed to its photosensitizing effect with subsequent UV radiation exposure through sunlight if the patient was to be without protective eye glasses, potentially causing macular toxicity. Till date, there have been no reports in the literature of any posterior segment ocular toxicity arising from methoxsalen use. Here, we describe a case of a bilateral macular toxicity in a middle-aged male treated with methoxsalen for vitiligo.", "affiliations": "Shri Bhagwan Mahavir Department of Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, India.;Shri Bhagwan Mahavir Department of Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, India.", "authors": "Maitray|Aditya|A|;Rishi|Pukhraj|P|", "chemical_list": "D017319:Photosensitizing Agents; D008730:Methoxsalen", "country": "India", "delete": false, "doi": "10.4103/ijo.IJO_413_17", "fulltext": "\n==== Front\nIndian J OphthalmolIndian J OphthalmolIJOIndian Journal of Ophthalmology0301-47381998-3689Medknow Publications & Media Pvt Ltd India 29133667IJO-65-124310.4103/ijo.IJO_413_17Brief CommunicationsMethoxsalen-induced macular toxicity Maitray Aditya Rishi Pukhraj Shri Bhagwan Mahavir Department of Vitreoretinal Services, Sankara Nethralaya, Chennai, Tamil Nadu, IndiaCorrespondence to: Dr. Pukhraj Rishi, Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, 18 College Road, Chennai - 600 006, Tamil Nadu, India. E-mail: docrishi@yahoo.co.in11 2017 65 11 1243 1245 22 5 2017 11 8 2017 Copyright: © 2017 Indian Journal of Ophthalmology2017This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.Psoralen compounds such as methoxsalen are photosensitizer agents used in conjunction with ultraviolet A (UVA) radiation exposure as photochemotherapy (Psoralens and ultraviolet-A therapy [PUVA therapy]) for certain epidermal skin disorders such as psoriasis and vitiligo. Methoxsalen has been shown to be associated with premature cataract formation by forming adducts with lens proteins following oral administration and subsequent UVA exposure. Hence, the use of UV-filtering glasses is recommended during PUVA therapy sessions. Ocular tissues can be exposed to its photosensitizing effect with subsequent UV radiation exposure through sunlight if the patient was to be without protective eye glasses, potentially causing macular toxicity. Till date, there have been no reports in the literature of any posterior segment ocular toxicity arising from methoxsalen use. Here, we describe a case of a bilateral macular toxicity in a middle-aged male treated with methoxsalen for vitiligo.\n\n8-methoxypsoralenmacular toxicitymethoxsalenpsoralens and ultraviolet-A exposure\n==== Body\nMethoxsalen or 8-methoxypsoralen (8-MOP) is a photosensitizer agent which is used in photochemotherapy in conjunction with exposing the affected skin to ultraviolet A (UVA) (320–400 nm) radiation (PUVA therapy) through lamps or sunlight for the treatment of certain epidermal proliferative disorders such as psoriasis, eczema, and vitiligo.[12] It intercalates into the DNA double helix and upon excitation by UVA, forms adducts with the DNA, thereby inducing the therapeutic and also the potential side effects.[3] It helps in the treatment of psoriasis by reducing the proliferation of skin cells and in vitiligo by increasing the number of melanocytes.[34] Methoxsalen has been shown to be present in the crystalline lens after oral administration and may form adducts with lens proteins on subsequent UVA exposure, leading to premature cataract formation. Hence, the use of UV-filtering glasses is recommended during PUVA therapy sessions.[4] Methoxsalen is metabolized by the liver and can be detected in plasma for 12–24 h before excretion in urine.[5] Thus, ocular tissues can be exposed to its photosensitizing effect with subsequent UV radiation exposure through sunlight if the patient was to be without protective eye glasses, potentially causing macular toxicity.\n\nTill date, there have been no reports of any ocular toxicity of the posterior segment arising from methoxsalen use (PubMed search). Here, we describe a case of a bilateral macular toxicity in a middle-aged male treated with methoxsalen for vitiligo.\n\nCase Report\nA 49-year-old Asian male presented with painless, progressive decrease in vision, and metamorphopsia in both eyes for a 3-year duration. He had no associated history of steroid intake, nyctalopia, or trauma. He had no significant family history. However, he had been using oral methoxsalen (8-MOP) 10–30 mg/day for vitiligo for the past 15 years without dermatologist supervision and without concomitant use of UV protective spectacles while on treatment. He was not being treated for any other conditions. He had been diagnosed elsewhere with choroidal neovascular membrane associated with age-related macular degeneration in both eyes and advised anti-vascular endothelial growth factor injections.\n\nOn general examination, he had depigmented patches over his ankles and forearms suggestive of vitiligo [Fig. 1a]. On ocular examination, his best-corrected visual acuity (BCVA) was 6/6 in both eyes, and his color vision was normal. Anterior segment examination was essentially normal. Fundus examination revealed yellowish-white deposits at the macula with a dull foveal reflex in both eyes [Fig. 1b and c]. Spectral-domain optical coherence tomography (SD-OCT) showed sub-retinal pigment epithelium (RPE) deposits with RPE elevation and thickening at the macula in both eyes [Fig. 1d]. At this stage, a diagnosis of MOP toxicity was entertained, keeping adult-onset foveomacular vitelliform dystrophy (AOFVD) as a close possible differential diagnosis. A standard full-field electroretinogram (ff-ERG), performed as per the International Society for Clinical Electrophysiology of Vision protocol, showed normal photopic and scotopic responses [Fig. 1e]. Multifocal electroretinogram (mf-ERG) revealed normal foveal, parafoveal, and perifoveal ring responses for both eyes [Fig. 1f]. Electrooculogram (EOG) showed normal response [Fig. 1g] with Arden ratio of 4.7 and 3.4 in the right and left eye, respectively. The patient was counseled, reassured, and asked to review annually. One year later, he presented with slight decrease in vision with BCVA of 6/9, N8 in both eyes, and clinically unaltered fundus findings [Fig. 2a and b]. Repeat SD-OCT showed similar findings [Fig. 2c]. Repeat mf-ERG revealed mild blunting of foveal peak in the right eye [Fig. 2d]. Fundus autofluorescence revealed hyperautofluorescence corresponding to the lesions in both eyes [Fig. 2e]. EOG was normal for both eyes with Arden ratio of 3.4 [Fig. 2f]. A diagnosis of methoxsalen-associated macular toxicity was arrived at, and the patient was advised to discontinue the drug and continue regular follow-up.\n\nFigure 1 (At first presentation): External photograph shows vitiligo patch (a) over the right ankle. Color fundus photograph of the right (b) and left (c) eye, respectively, showing yellowish deposits at the macula with dull foveal reflex. Spectral-domain optical coherence tomography shows sub-retinal pigment epithelium deposits with retinal pigment epithelium elevation and thickening (d) at the macula in both eyes. Full-field electroretinogram of both eyes showing normal photopic and scotopic responses (e). Multifocal-electroretinogram shows normal foveal, parafoveal, and perifoveal responses in both eyes (f). Normal electrooculogram of both eyes (g)\n\nFigure 2 (At 1-year follow-up): Color fundus photograph of the right (a) and left (b) eye, respectively, appears unaltered compared to previous visit. Spectral-domain optical coherence tomography shows sub-retinal pigment epithelium deposits (c) and retinal pigment epithelium elevation and thickening at the macula (OD > OS). Multifocal-electroretinogram shows blunted foveal peak in the right eye (d). Fundus autofluorescence image (e) shows hyperautofluorescence at the macula in both eyes corresponding to the clinically visible lesions. Electrooculogram is normal in both eyes (f)\n\nDiscussion\nA variety of systemic medications are known to cause retinal toxicity. In most instances, the resulting visual dysfunction is reversible on discontinuation of the drug, especially if recognized at an early stage. However, in some cases, delayed recognition can lead to progressive and/or irreversible retinal dysfunction causing advanced visual impairment.[6] Medications commonly known to produce retinal toxicity include chloroquine and hydroxychloroquine, vigabatrin, deferoxamine, ethambutol, interferon-α, tamoxifen, digoxin, sildenafil, canthaxanthin, aminoglycosides, and amiodarone.[67]\n\nPUVA therapy involves administering of oral 8-MOP in dose of 0.3–0.6 mg/kg followed 1–2 h later by UVA exposure (starting at 0.5 J/cm2) when the drug generally attains peak plasma levels.[2] Patients generally require several weekly sessions for a long time for improvement of their cutaneous disease.[5] Significant levels of methoxsalen have been demonstrated in aqueous humor, crystalline lens, vitreous, and retinal tissue in guinea pigs 3 h following oral administration.[8] Hence, ocular protection from UVA in using protective eye glasses is recommended during and up to 18 h following PUVA therapy sessions.\n\nLiterature is scarce about adverse effects of oral 8-MOP and UVA exposure (PUVA) on macular function. In 1986, Cox et al. reported a series of 46 patients on PUVA therapy with normal ophthalmologic assessment.[4] More recently, Shoeibi et al. studied the effect of PUVA on the retina in 40 eyes with ERG at baseline and at 6-month follow-up. They found no significant difference in photopic or scotopic responses.[9] In their study, the patients were instructed to wear UV protective eyeglasses for up to 18 h after each PUVA session.\n\nHowever, our patient was using oral methoxsalen 10–30 mg daily for 15 years in an unsupervised manner, without using protective eyewear. Although he did not have UVA sessions, he did have a history of abundant sunlight exposure. Hence, even though his ff-ERG was apparently normal, the reduced foveal response on mf-ERG and a documented reduction in visual acuity pointed toward macular toxicity. Since 8-MOP acts by stimulating melanocyte proliferation (basis of its therapeutic use in vitiligo), it is possible that it may induce changes in the metabolically active RPE at the macula, subsequently leading to the clinical picture as seen in our case. AOFVD is a close differential diagnosis in this case. AOFVD typically has late onset (4–6th decade), typically showing bilateral but asymmetric yellowish elevated subretinal lesions in the foveal or perifoveal region, often with central pigmentation. Patients with AOFVD are usually asymptomatic or have mild blurring of vision, mild metamorphopsia, and/or small central or paracentral scotomas. Genetic testing to rule out BEST1 or PRPH 2/RDS gene mutation could further help in identifying the condition.[10]\n\nConclusion\nMethoxsalen can cause bilateral macular toxicity. Further studies on potential long-term effects of psoralen therapy on macular function are required to understand this better.\n\nFinancial support and sponsorship\nNil.\n\nConflicts of interest\nThere are no conflicts of interest.\n==== Refs\n1 Brickl R Schmid J Koss FW Clinical pharmacology of oral psoralen drugs Photodermatol 1984 1 174 86 6397736 \n2 Zarebska Z Waszkowska E Caffieri S Dall’Acqua F PUVA (psoralen+ UVA) photochemotherapy: Processes triggered in the cells Farmaco 2000 55 515 20 11132728 \n3 Cimino GD Gamper HB Isaacs ST Hearst JE Psoralens as photoactive probes of nucleic acid structure and function: Organic chemistry, photochemistry, and biochemistry Annu Rev Biochem 1985 54 1151 93 2411210 \n4 Cox NH Jones SK Downey DJ Tuyp EJ Jay JL Moseley H Cutaneous and ocular side-effects of oral photochemotherapy: Results of an 8-year follow-up study Br J Dermatol 1987 116 145 52 3828211 \n5 Hönigsmann H Phototherapy for psoriasis Clin Exp Dermatol 2001 26 343 50 11422187 \n6 Santaella RM Fraunfelder FW Ocular adverse effects associated with systemic medications: Recognition and management Drugs 2007 67 75 93 17209665 \n7 Dettoraki M Moschos MM The role of multifocal electroretinography in the assessment of drug-induced retinopathy: A review of the literature Ophthalmic Res 2016 56 169 77 27351191 \n8 Chakrabarti SG Halder RM Johnson BA Minus HR Pradhan TK Kenney JA Jr 8-Methoxypsoralen levels in blood of vitiligo patients and in skin, ophthalmic fluids, and ocular tissues of the guinea pig J Invest Dermatol 1986 87 276 9 3734475 \n9 Shoeibi N Taheri A Nikandish M Omidtabrizi A Khosravi N Kadkhoda M Effect of oral photochemotherapy (8-methoxypsoralen + UVA) on the electrophysiologic function of retina Cutan Ocul Toxicol 2016 35 104 9 25942691 \n10 Grob S Yonekawa Y Eliott D Multimodal imaging of adult-onset foveomacular vitelliform dystrophy Saudi J Ophthalmol 2014 28 104 10 24843302\n\n", "fulltext_license": "CC BY-NC-SA", "issn_linking": "0301-4738", "issue": "65(11)", "journal": "Indian journal of ophthalmology", "keywords": null, "medline_ta": "Indian J Ophthalmol", "mesh_terms": "D004585:Electrooculography; D004596:Electroretinography; D006801:Humans; D008266:Macula Lutea; D008297:Male; D008730:Methoxsalen; D008875:Middle Aged; D017319:Photosensitizing Agents; D012164:Retinal Diseases; D055213:Retinal Pigment Epithelium; D014792:Visual Acuity; D014820:Vitiligo", "nlm_unique_id": "0405376", "other_id": null, "pages": "1243-1245", "pmc": null, "pmid": "29133667", "pubdate": "2017-11", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "25942691;2411210;24843302;17209665;6397736;11132728;3734475;11422187;27351191;3828211", "title": "Methoxsalen-induced macular toxicity.", "title_normalized": "methoxsalen induced macular toxicity" }

[ { "companynumb": "IN-BAUSCH-BL-2018-000738", "fulfillexpeditecriteria": "1", "occurcountry": "IN", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "METHOXSALEN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "009048", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10-30 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "VITILIGO", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "8-MOP" } ], "patientagegroup": null, "patientonsetage": "49", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Retinal toxicity", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Wrong technique in product usage process", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MAITRAY A, RISHI P. METHOXSALEN-INDUCED MACULAR TOXICITY. INDIAN JOURNAL OF OPHTHALMOLOGY. 2017 NOV?65:1243-1245.", "literaturereference_normalized": "methoxsalen induced macular toxicity", "qualification": "3", "reportercountry": "IN" }, "primarysourcecountry": "IN", "receiptdate": "20180116", "receivedate": "20180116", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14393741, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180509" } ]

{ "abstract": "A female patient with systemic lupus erythematosus developed an atypical femoral fracture of the left femur after 5 years of glucocorticoid and alendronate therapy. We performed intramedullary nailing. However, 1 week later, we performed a revision surgery using a locking plate and an iliac bone graft because of displacement at the fracture site. At this stage, alendronate was discontinued and daily teriparatide was introduced and continued for 24 months. Twenty months after the revision surgery, a re-revision surgery was performed with an iliac bone graft because of breakage of the locking plate and fracture non-union. Fracture healing was eventually obtained 15 months after the re-revision surgery. Biopsies of the ilium before the treatment and 20 months after daily teriparatide treatment were evaluated. The histology revealed that proliferating osteoid and cuboidal osteoblasts were detected around the osteoid tissue after teriparatide treatment. Bone histomorphometry findings showed that bone volume parameters and osteoid parameters prominently increased with the teriparatide treatment, but not bone resorption parameters. Laboratory findings revealed the elevation of bone-specific alkaline phosphatase (24 U/L at 7 months) compared to its pre-teriparatide level (8.1 U/L) and increased bone mineral density of the hip (from -0.2 to 0.0 in T-score). These data indicated that the discontinuation of alendronate and initiation of teriparatide treatment activated bone-forming ability in our patient and may have contributed to fracture healing.", "affiliations": "Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.;Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.;Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.;Health Administration Center, Niigata University, Niigata, Japan.;Division of Orthopedic Surgery, Seirei Hamamatsu Hospital, Hamamatsu, Japan.;Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.", "authors": "Kondo|Naoki|N|;Miyasaka|Dai|D|;Watanabe|Yo|Y|;Sato|Hiroe|H|;Kanda|Toshihiro|T|;Endo|Naoto|N|", "chemical_list": "D050071:Bone Density Conservation Agents; D019379:Teriparatide; D019386:Alendronate", "country": "England", "delete": false, "doi": "10.1080/24725625.2019.1650992", "fulltext": null, "fulltext_license": null, "issn_linking": "2472-5625", "issue": "4(1)", "journal": "Modern rheumatology case reports", "keywords": "Atypical femoral fracture; bone histomorphometry; non-union; osteoid parameters; teriparatide", "medline_ta": "Mod Rheumatol Case Rep", "mesh_terms": "D019386:Alendronate; D001706:Biopsy; D050071:Bone Density Conservation Agents; D004198:Disease Susceptibility; D005260:Female; D005264:Femoral Fractures; D017102:Fracture Healing; D006801:Humans; D010012:Osteogenesis; D019379:Teriparatide; D016896:Treatment Outcome", "nlm_unique_id": "101761026", "other_id": null, "pages": "141-146", "pmc": null, "pmid": "33086957", "pubdate": "2020-01", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Atypical femoral fracture associated with delayed union for which the cessation of alendronate and daily administration of teriparatide contributed to fracture healing: histopathological evidence of the enhancement in bone formation parameters.", "title_normalized": "atypical femoral fracture associated with delayed union for which the cessation of alendronate and daily administration of teriparatide contributed to fracture healing histopathological evidence of the enhancement in bone formation parameters" }

[ { "companynumb": "NVSC2020JP068686", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "017469", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG, QD EVERY 4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "ALENDRONATE SODIUM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "75871", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "35 MG, QW", "drugenddate": null, "drugenddateformat": null, "drugindication": "OSTEOPOROSIS", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "35", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALENDRONATE SODIUM TRIHYDRATE" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "017469", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "017469", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60 MG, QD FOR 1MONTH AT FIRST", "drugenddate": null, "drugenddateformat": null, "drugindication": "SYSTEMIC LUPUS ERYTHEMATOSUS", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "60", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "017469", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MG, QD EVERY 4 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." } ], "patientagegroup": null, "patientonsetage": "49", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Femur fracture", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Walking disability", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pain in extremity", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Osteoporosis", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "KONDOA N, MIYASAKAA D, WATANABEA Y, SATOB H, KANDA T, ENDO N ET AL.. ATYPICAL FEMORAL FRACTURE ASSOCIATED WITH DELAYED UNION FOR WHICH THE CESSATION OF ALENDRONATE AND DAILY ADMINISTRATION OF TERIPARATIDE CONTRIBUTED TO FRACTURE HEALING: HISTOPATHOLOGICAL EVIDENCE OF THE ENHANCEMENT IN BONE FORMATION PARAMETERS. MODERN RHEUMATOLOGY CASE REPORTS. 2020?4(1):141-6", "literaturereference_normalized": "atypical femoral fracture associated with delayed union for which the cessation of alendronate and daily administration of teriparatide contributed to fracture healing histopathological evidence of the enhancement in bone formation parameters", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20200313", "receivedate": "20200313", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17540652, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20200409" } ]

{ "abstract": "BACKGROUND\nInterferon (IFN) is a treatment option for both mycosis fungoides (MF) and hepatitis C virus (HCV) infection. Chemotherapy and anti-HCV treatment are generally not administered concurrently for fear of overlapping side effects.\n\n\nOBJECTIVE\nHerein, we report on a subset of patients who received IFN-containing therapy for MF and HCV infection simultaneously. We aimed to evaluate whether concomitant treatment for MF and HCV is effective and well tolerated.\n\n\nMETHODS\nWe reviewed the records of patients who were seen at MD Anderson Cancer Center from 2008 to 2013 with histologically confirmed MF and chronic HCV infection, and were treated with simultaneous focus on both diseases.\n\n\nRESULTS\nSix HCV-infected patients with MF received simultaneous anti-HCV and anti-MF treatment with IFN-containing therapy. Two patients achieved sustained virological response (regarded as virological cure). They both received antiviral combination therapy with ribavirin. All patients experienced some improvement of their cutaneous lesions, with two of them achieving complete MF remission. All six patients developed side effects while receiving treatment; two of them had grade 4 toxic effects requiring treatment discontinuation.\n\n\nCONCLUSIONS\nIFN-based therapy can be administered for MF and HCV infection concurrently to provide not only virological but also oncological benefits to chronically HCV-infected MF patients. However, this regimen is poorly tolerated. Further studies are warranted in this patient population, using different treatment combinations with improved efficacy, safety, and tolerability.", "affiliations": "Unit 1460, Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.", "authors": "Kyvernitakis|Andreas|A|;Duvic|Madeleine|M|;Mahale|Parag|P|;Torres|Harrys A|HA|", "chemical_list": "D000970:Antineoplastic Agents; D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin", "country": "New Zealand", "delete": false, "doi": "10.1007/s40257-014-0084-6", "fulltext": null, "fulltext_license": null, "issn_linking": "1175-0561", "issue": "15(5)", "journal": "American journal of clinical dermatology", "keywords": null, "medline_ta": "Am J Clin Dermatol", "mesh_terms": "D000328:Adult; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic; D006801:Humans; D016898:Interferon-alpha; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides; D012074:Remission Induction; D012254:Ribavirin; D012878:Skin Neoplasms; D016896:Treatment Outcome", "nlm_unique_id": "100895290", "other_id": null, "pages": "451-6", "pmc": null, "pmid": "24934807", "pubdate": "2014-10", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Interferon-based treatment for patients with mycosis fungoides and hepatitis C virus infection: a case series.", "title_normalized": "interferon based treatment for patients with mycosis fungoides and hepatitis c virus infection a case series" }

[ { "companynumb": "US-VERTEX PHARMACEUTICALS-2015-000057", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "TELAPREVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "201917", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INCIVEK" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "PEGINTERFERON ALFA-2A OR PEGINTERFERON ALFA-2B" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "180 MCG/ML", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEGYLATED INTERFERON ALPHA NOS" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "PEGINTERFERON ALFA-2A OR PEGINTERFERON ALFA-2B" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEGYLATED INTERFERON ALPHA NOS" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RIBAVIRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "180 UNK, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIBAVIRIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RIBAVIRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIBAVIRIN." } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pruritus", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Anaemia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Leukopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Thrombocytopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Skin lesion", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "KYVERNITAKIS A, DUVIC M, MAHALE P, AND TORRES HA. INTERFERON-BASED TREATMENT FOR PATIENTS WITH MYCOSIS FUNGOIDES AND HEPATITIS C VIRUS INFECTION: A CASE SERIES. AM J CLIN DERMATOL. 2014;15 (5):451-456", "literaturereference_normalized": "interferon based treatment for patients with mycosis fungoides and hepatitis c virus infection a case series", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150109", "receivedate": "20150109", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10700824, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "US-ROCHE-1431303", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "PEGINTERFERON ALFA-2A" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "103964", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "FOR 12 WEEKS, DOSE REDUCED", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEG-INTERFERON ALFA 2A" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TELAPREVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TELAPREVIR" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "TELAPREVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "MYCOSIS FUNGOIDES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TELAPREVIR" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "PEGINTERFERON ALFA-2A" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "103964", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "180 MCG/ML PER WEEK FOR 12 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "MYCOSIS FUNGOIDES", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEG-INTERFERON ALFA 2A" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "RIBAVIRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "021511", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "FOR 12 WEEKS, DOSE REDUCED", "drugenddate": null, "drugenddateformat": null, "drugindication": "MYCOSIS FUNGOIDES", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIBAVIRIN." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "RIBAVIRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "021511", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "FOR 12 WEEKS", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIBAVIRIN." } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombocytopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Anaemia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Leukopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "KYVERNITAKIS A, DUVIC M, MAHALE P AND TORRES H. INTERFERON-BASED TREATMENT FOR PATIENTS WITH MYCOSIS FUNGOIDES AND HEPATITIS C VIRUS INFECTION: A CASE SERIES. AMERICAN JOURNAL OF CLINICAL DERMATOLOGY 2014 OCT;15 (5):451-456.", "literaturereference_normalized": "interferon based treatment for patients with mycosis fungoides and hepatitis c virus infection a case series", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150605", "receivedate": "20140708", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 10283180, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150821" }, { "companynumb": "US-TEVA-534682USA", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "PEGINTERFERON ALFA-2A OR PEGINTERFERON ALFA-2B" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "180 MCG/ML, WEEKLY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEGYLATED INTERFERON ALPHA NOS" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TELAPREVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "180 MCG/ML, WEEKLY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TELAPREVIR" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "RIBAVIRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "076277", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "180 MCG/ML, WEEKLY", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIBAVIRIN." } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pancytopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "KYVERNITAKIS A, DUVIC M, MAHALE P, TORRES HA. INTERFERON-BASED TREATMENT FOR PATIENTS WITH MYCOSIS FUNGOIDES AND HEPATITIS C VIRUS INFECTION: A CASE SERIES. AM-J-CLIN-DERM 2014; 15(5) 451-456", "literaturereference_normalized": "interferon based treatment for patients with mycosis fungoides and hepatitis c virus infection a case series", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150116", "receivedate": "20150116", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10717671, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" }, { "companynumb": "PHHY2015US001442", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "RIBAVIRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "076192", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIBAVIRIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TELAPREVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TELAPREVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MECHLORETHAMINE OXIDE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CREAM", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "SKIN LESION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NITROGEN MUSTARD" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "PEGINTERFERON ALFA-2A OR PEGINTERFERON ALFA-2B" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "180 MCG/ML, QW", "drugenddate": null, "drugenddateformat": null, "drugindication": "CHRONIC HEPATITIS C", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PEGYLATED INTERFERON ALPHA NOS" } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Thrombocytopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Leukopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Pancytopenia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Anaemia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "KYVERNITAKIS A, DUVIC M, MAHALE P, TORRES HA.. INTERFERON-BASED TREATMENT FOR PATIENTS WITH MYCOSIS FUNGOIDES AND HEPATITIS C VIRUS INFECTION: A CASE SERIES.. J-CLIN-DERM. 2014;15(5):451-56", "literaturereference_normalized": "interferon based treatment for patients with mycosis fungoides and hepatitis c virus infection a case series", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150112", "receivedate": "20150112", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10705321, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150721" } ]

{ "abstract": "Cardiotoxicity induced by 5-fluorouracil (5-FU) is well known but poorly understood. In this study, we undertook ECG recording (Holter) and analyses of the biomarkers troponin and copeptin in patients receiving 5-FU to increase our understanding of the cardiotoxicity.\n\n\n\nPatients with colorectal or anal cancer that received first-time treatment with 5-FU-based chemotherapy were prospectively included. Holter recording, clinical evaluation, 12-lead electrocardiogram, and assessment of plasma concentrations of troponin I and copeptin were performed before (control) and during 5-FU treatment (intervention).\n\n\n\nA total of 108 patients were included, 82 with colorectal and 26 with anal cancer. The proportion of patients with myocardial ischemia on Holter recording was significantly higher during the first 5-FU infusion (14.1%) than before (3.7%; p = .001). The ischemic burden per day (p = .001), the number of ST depression episodes per day (p = .003), and the total duration of ischemic episodes per day (p = .003) were higher during the first 5-FU infusion than before, as was plasma copeptin (p < .001), whereas plasma troponin I was similar (p > 0.999). Six patients (5.6%) developed acute coronary syndromes and two (1.8%) developed symptomatic arrhythmias during 5-FU treatment.\n\n\n\n5-FU infusion is associated with an increase in the number of patients with myocardial ischemia on Holter recording. According to biomarker analyses, 5-FU is associated with an increase in copeptin, but rarely with increases in cardiac troponin I. However, 5%-6% of the patients developed acute coronary syndromes during treatment with 5-FU.\n\n\n\nSymptomatic 5-fluorouracil (5-FU) cardiotoxicity occurs in 0.6%-19% of patients treated with this drug, but a small electrocardiographic (Holter) study has revealed silent myocardial ischemia in asymptomatic patients, suggesting a more prevalent subclinical cardiac influence. This study demonstrated a significant increase in the number of patients with myocardial ischemia on Holter recording during 5-FU treatment and an increase in ischemic burden. Cardiac biomarker analyses suggested that 5-FU infusion results in endogenous stress (increased copeptin) but rarely induces myocyte injury (no change in troponin). These findings suggest a more prevalent cardiac influence from 5-FU and that Holter recording is an important tool in the evaluation of patients with suspected cardiotoxicity from 5-FU.", "affiliations": "Departments of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.;Departments of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.;Departments of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.;Departments of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.;Departments of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.;Departments of Medicine, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.;Departments of Hematology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.;Departments of Clinical Biochemistry, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.;Departments of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.;Departments of Oncology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark.", "authors": "Dyhl-Polk|Anne|A|0000-0003-2335-8219;Schou|Morten|M|;Vistisen|Kirsten K|KK|;Sillesen|Anne-Sophie|AS|;Serup-Hansen|Eva|E|;Faber|Jens|J|;Klausen|Tobias W|TW|;Bojesen|Stig E|SE|;Vaage-Nilsen|Merete|M|;Nielsen|Dorte L|DL|", "chemical_list": "D015415:Biomarkers; D005472:Fluorouracil", "country": "United States", "delete": false, "doi": "10.1002/onco.13536", "fulltext": null, "fulltext_license": null, "issn_linking": "1083-7159", "issue": "26(3)", "journal": "The oncologist", "keywords": "5-Flourouracil; Anal cancer; Cardiotoxicity; Colorectal cancer; Myocardial ischemia", "medline_ta": "Oncologist", "mesh_terms": "D015415:Biomarkers; D004562:Electrocardiography; D005472:Fluorouracil; D006801:Humans; D017202:Myocardial Ischemia; D011446:Prospective Studies", "nlm_unique_id": "9607837", "other_id": null, "pages": "e403-e413", "pmc": null, "pmid": "32959474", "pubdate": "2021-03", "publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't", "references": "29977352;2493043;26980771;30011137;8277098;15774494;9538168;9053508;23019400;14749623;8080545;24215751;21890090;25196083;11081567;28886621;24558023;23298558;18672166;28784609;11867655;24731654;25001200;3383411;21275498;19309247;17420344;21928176;26320110;25186061;18291667;17636329;7977093;23894863;28062612;12963683;26762848;14510654;2466960;15231861;20653710;9014794;23582737;27334640;21139111;28623776;15033676;21766239;24082383;17493091;10569322;18264205;16210935;2040332;27380959;19415535;30396850;14976858;15725158;16269513;28881920;17649788", "title": "Myocardial Ischemia Induced by 5-Fluorouracil: A Prospective Electrocardiographic and Cardiac Biomarker Study.", "title_normalized": "myocardial ischemia induced by 5 fluorouracil a prospective electrocardiographic and cardiac biomarker study" }

[ { "companynumb": "DK-ACCORD-204359", "fulfillexpeditecriteria": "1", "occurcountry": "DK", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "040743", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NEOPLASM MALIGNANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Acute coronary syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "DYHL-POLK A, SCHOU M, VISTISEN KK, SILLESEN AS, SERUP-HANSEN E, FABER J. ET. AL. MYOCARDIAL ISCHEMIA INDUCED BY 5-FLUOROURACIL: A PROSPECTIVE ELECTROCARDIOGRAPHIC AND CARDIAC BIOMARKER STUDY. ONCOLOGIST. 2020 SEP 21", "literaturereference_normalized": "myocardial ischemia induced by 5 fluorouracil a prospective electrocardiographic and cardiac biomarker study", "qualification": "3", "reportercountry": "DK" }, "primarysourcecountry": "DK", "receiptdate": "20201008", "receivedate": "20201008", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18359554, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" }, { "companynumb": "DK-ACCORD-204363", "fulfillexpeditecriteria": "1", "occurcountry": "DK", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "040743", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": "96-HOUR INFUSION", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Supraventricular tachycardia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "DYHL-POLK A, SCHOU M, VISTISEN KK, SILLESEN AS, SERUP-HANSEN E, FABER J. ET. AL. MYOCARDIAL ISCHEMIA INDUCED BY 5-FLUOROURACIL: A PROSPECTIVE ELECTROCARDIOGRAPHIC AND CARDIAC BIOMARKER STUDY. ONCOLOGIST. 2020 SEP 21", "literaturereference_normalized": "myocardial ischemia induced by 5 fluorouracil a prospective electrocardiographic and cardiac biomarker study", "qualification": "3", "reportercountry": "DK" }, "primarysourcecountry": "DK", "receiptdate": "20201008", "receivedate": "20201008", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18359910, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210114" }, { "companynumb": "DK-ACCORD-204364", "fulfillexpeditecriteria": "1", "occurcountry": "DK", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FLUOROURACIL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "040743", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INFUSION", "drugdosagetext": "96-HOUR INFUSION", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUOROURACIL." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Ventricular tachycardia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "DYHL-POLK A, SCHOU M, VISTISEN KK, SILLESEN AS, SERUP-HANSEN E, FABER J. ET. AL. MYOCARDIAL ISCHEMIA INDUCED BY 5-FLUOROURACIL: A PROSPECTIVE ELECTROCARDIOGRAPHIC AND CARDIAC BIOMARKER STUDY. ONCOLOGIST. 2020 SEP 21", "literaturereference_normalized": "myocardial ischemia induced by 5 fluorouracil a prospective electrocardiographic and cardiac biomarker study", "qualification": "3", "reportercountry": "DK" }, "primarysourcecountry": "DK", "receiptdate": "20201008", "receivedate": "20201008", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 18359890, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" } ]

{ "abstract": "This article presents the case of a multimorbid male patient with an accidental dabigatran overdose caused by kidney failure in the context of an acute intestinal disorder. After effective initial antagonizing of the dabigatran effect using idarucizumab a dabigatran rebound was detected caused by a single hemodialysis leading to a severe intrapulmonary hemorrhage. As dabigatran plasma level testing was not available and conventional coagulation analysis was out of interpretable range due to the impact of dabigatran, continuous thrombelastography (TEG) was used to detect the effect of dabigatran and monitor the treatment results. The most significant parameter used in the kaolin activated clotting time was the R‑time parameter, which was massively prolonged by the interrupted coagulation cascade.", "affiliations": "Klinik für Anästhesie, operative Intensiv- und Palliativmedizin, Klinikum Würzburg Mitte - Standort Juliusspital, Juliuspromenade 19, 97070, Würzburg, Deutschland. k.lorenz@kwm-klinikum.de.;Klinik für Anästhesie, operative Intensiv- und Palliativmedizin, Klinikum Würzburg Mitte - Standort Juliusspital, Juliuspromenade 19, 97070, Würzburg, Deutschland.", "authors": "Lorenz|K-W|KW|;Schäfer|R|R|", "chemical_list": "D061067:Antibodies, Monoclonal, Humanized; C000594745:idarucizumab; D000069604:Dabigatran", "country": "Germany", "delete": false, "doi": "10.1007/s00101-020-00801-x", "fulltext": null, "fulltext_license": null, "issn_linking": "0003-2417", "issue": "69(8)", "journal": "Der Anaesthesist", "keywords": "Hemodialysis; Idarucizumab; Intoxication; R-Time; Thrombin-Inhibitor", "medline_ta": "Anaesthesist", "mesh_terms": "D058186:Acute Kidney Injury; D061067:Antibodies, Monoclonal, Humanized; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D000069604:Dabigatran; D062787:Drug Overdose; D006470:Hemorrhage; D006801:Humans; D008297:Male; D006435:Renal Dialysis; D013916:Thrombelastography", "nlm_unique_id": "0370525", "other_id": null, "pages": "573-578", "pmc": null, "pmid": "32564188", "pubdate": "2020-08", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "TEG-guided treatment of a dabigatran overdose in a patient with acute kidney failure.", "title_normalized": "teg guided treatment of a dabigatran overdose in a patient with acute kidney failure" }

[ { "companynumb": "DE-B.I. PHARMACEUTICALS,INC./RIDGEFIELD-2020-BI-055701", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "ASPIRIN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG TWICE DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "2018", "drugstartdateformat": "602", "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ASPIRIN [ACETYLSALICYLIC ACID]" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DABIGATRAN ETEXILATE MESYLATE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "022512", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "150", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PRADAXA" } ], "patientagegroup": "6", "patientonsetage": "68", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pulmonary haemorrhage", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LORENZ K-W? SCHAFER, R. TEG-GUIDED TREATMENT OF A DABIGATRAN OVERDOSE IN A PATIENT WITH ACUTE KIDNEY FAILURE. ANAESTHESIST 2020, V69, P573-578", "literaturereference_normalized": "teg guided treatment of a dabigatran overdose in a patient with acute kidney failure", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20201026", "receivedate": "20201026", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18428392, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210114" }, { "companynumb": "DE-ALKEM LABORATORIES LIMITED-DE-ALKEM-2022-00451", "fulfillexpeditecriteria": "1", "occurcountry": "DE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DABIGATRAN ETEXILATE MESYLATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "208040", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "150 MILLIGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "Product used for unknown indication", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "150", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DABIGATRAN ETEXILATE MESYLATE" } ], "patientagegroup": null, "patientonsetage": "68", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pulmonary haemorrhage", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Overdose", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Lorenz KW, Schafer R. TEG-guided treatment of a dabigatran overdose in a patient with acute kidney failure. Anaesthesist. 2020;69(8):573-578", "literaturereference_normalized": "teg guided treatment of a dabigatran overdose in a patient with acute kidney failure", "qualification": "3", "reportercountry": "DE" }, "primarysourcecountry": "DE", "receiptdate": "20220331", "receivedate": "20220331", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20656511, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" } ]

{ "abstract": "BACKGROUND\nHIV genetic diversity implicates major challenges for the control of viral infection by the immune system and for the identification of an effective immunotherapeutic strategy. With the present case report we underline as HIV evolution could be effectively halted by early antiretroviral treatment (eART). Few cases supported this evidence due to the difficulty of performing amplification and sequencing analysis in long-term viral suppressed patients. Here, we reported the case of limited HIV-1 viral evolution over time in a successful early treated child.\n\n\nMETHODS\nA perinatally HIV-1 infected infant was treated within 7 weeks of age with zidovudine, lamivudine, nevirapine and lopinavir/ritonavir. At antiretroviral treatment (ART) initiation HIV-1 viral load (VL) and CD4 percentage were >500,000 copies/ml and 35%, respectively. Plasma genotypic resistance test showed a wild-type virus. The child reached VL undetectability after 33 weeks of combination antiretroviral therapy (cART) since he maintained a stable VL <40copies/ml. After 116 weeks on ART we were able to perform amplification and sequencing assay on the plasma virus. At this time VL was <40 copies/ml and CD4 percentage was 40%. Again the genotypic resistance test revealed a wild-type virus. The phylogenetic analysis performed on the HIV-1 pol sequences of the mother and the child revealed that sequences clustered with C subtype reference strains and formed a monophyletic cluster distinct from the other C sequences included in the analysis (bootstrap value >90%). Any major evolutionary divergence was detected.\n\n\nCONCLUSIONS\neART limits the viral evolution avoiding the emergence of new viral variants. This result may have important implications in host immune control and may sustain the challenge search of new personalized immunotherapeutic approaches to achieve a prolonged viral remission.", "affiliations": "Academic Department of Pediatrics, Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, P.zza Sant'Onofrio, 4-00165, Rome, Italy. paolo.palma@opbg.net.;Academic Department of Pediatrics, Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, P.zza Sant'Onofrio, 4-00165, Rome, Italy.;Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy.;Academic Department of Pediatrics, Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, P.zza Sant'Onofrio, 4-00165, Rome, Italy.;Academic Department of Pediatrics, Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, P.zza Sant'Onofrio, 4-00165, Rome, Italy.;Clinical Department, National Institute for Infectious Diseases 'L. Spallanzani', Rome, Italy.;Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy.;Academic Department of Pediatrics, Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, P.zza Sant'Onofrio, 4-00165, Rome, Italy.;Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy.;Academic Department of Pediatrics, Unit of Immune and Infectious Diseases, Children's Hospital Bambino Gesù, P.zza Sant'Onofrio, 4-00165, Rome, Italy. stefania.bernardi@opbg.net.", "authors": "Palma|Paolo|P|;Zangari|Paola|P|;Alteri|Claudia|C|;Tchidjou|Hyppolite K|HK|;Manno|Emma Concetta|EC|;Liuzzi|Giuseppina|G|;Perno|Carlo Federico|CF|;Rossi|Paolo|P|;Bertoli|Ada|A|;Bernardi|Stefania|S|", "chemical_list": "D019380:Anti-HIV Agents; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019829:Nevirapine; D019438:Ritonavir", "country": "England", "delete": false, "doi": "10.1186/s12879-016-2092-z", "fulltext": "\n==== Front\nBMC Infect DisBMC Infect. DisBMC Infectious Diseases1471-2334BioMed Central London 209210.1186/s12879-016-2092-zCase ReportEarly antiretroviral treatment (eART) limits viral diversity over time in a long-term HIV viral suppressed perinatally infected child Palma Paolo 0039 (0)6 68592793paolo.palma@opbg.net 12Zangari Paola paolazangari@hotmail.com 12Alteri Claudia claudia.alteri@uniroma2.it 3Tchidjou Hyppolite K. hyppolite.tchidjouku@opbg.net 1Manno Emma Concetta emma_m@hotmail.it 1Liuzzi Giuseppina giuseppina.liuzzi@inmi.it 4Perno Carlo Federico cf.perno@uniroma2.it 3Rossi Paolo paolo.rossi@opbg.net 1Bertoli Ada bertoli@uniroma2.it 3Bernardi Stefania stefania.bernardi@opbg.net 11 Academic Department of Pediatrics, Unit of Immune and Infectious Diseases, Children’s Hospital Bambino Gesù, P.zza Sant’Onofrio, 4-00165 Rome, Italy 2 Research Unit in Congenital and Perinatal Infections, Children’s Hospital Bambino Gesù, Rome, Italy 3 Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy 4 Clinical Department, National Institute for Infectious Diseases ’L. Spallanzani’, Rome, Italy 9 12 2016 9 12 2016 2016 16 7426 5 2016 3 12 2016 © The Author(s). 2016\nOpen AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background\nHIV genetic diversity implicates major challenges for the control of viral infection by the immune system and for the identification of an effective immunotherapeutic strategy. With the present case report we underline as HIV evolution could be effectively halted by early antiretroviral treatment (eART). Few cases supported this evidence due to the difficulty of performing amplification and sequencing analysis in long-term viral suppressed patients. Here, we reported the case of limited HIV-1 viral evolution over time in a successful early treated child.\n\nCase presentation\nA perinatally HIV-1 infected infant was treated within 7 weeks of age with zidovudine, lamivudine, nevirapine and lopinavir/ritonavir. At antiretroviral treatment (ART) initiation HIV-1 viral load (VL) and CD4 percentage were >500,000 copies/ml and 35%, respectively. Plasma genotypic resistance test showed a wild-type virus. The child reached VL undetectability after 33 weeks of combination antiretroviral therapy (cART) since he maintained a stable VL <40copies/ml. After 116 weeks on ART we were able to perform amplification and sequencing assay on the plasma virus. At this time VL was <40 copies/ml and CD4 percentage was 40%. Again the genotypic resistance test revealed a wild-type virus. The phylogenetic analysis performed on the HIV-1 pol sequences of the mother and the child revealed that sequences clustered with C subtype reference strains and formed a monophyletic cluster distinct from the other C sequences included in the analysis (bootstrap value >90%). Any major evolutionary divergence was detected.\n\nConclusions\neART limits the viral evolution avoiding the emergence of new viral variants. This result may have important implications in host immune control and may sustain the challenge search of new personalized immunotherapeutic approaches to achieve a prolonged viral remission.\n\nElectronic supplementary material\nThe online version of this article (doi:10.1186/s12879-016-2092-z) contains supplementary material, which is available to authorized users.\n\nKeywords\nHIVEarly antiretroviral treatmentChildrenViral evolutionImmunotherapyRicerca finalizzata Ministero della Salute per OPBG201201X002919Rossi Paolo issue-copyright-statement© The Author(s) 2016\n==== Body\nBackground\nHIV-1 infection is characterized by broad genetic diversity and rapid evolution that influence the pathogenesis, transmission and clinical management of the infection [1]. Such high genetic variability represents also a major drawback in the identification of an effective immunotherapeutic strategy. Genetically homogeneous virus population has been found at birth in perinatally HIV infected infants, in contrast to the heterogeneous virus populations often found in their infected mothers [2]. Similarly, a uniform viral population has been observed in newly infected adults short after transmission [3]. These observations led to the hypothesis that an early intervention with cART could limit viral evolution. Indeed, the homogeneity of viral sequences in HIV infected individuals treated during early infection compared with higher diversity in late treated patients has been recently confirmed in adult populations [4–6]. Although the relationship between the viral evolutionary dynamics and timing of treatment has been explored to some extent in adult less is known about this relationship during paediatric HIV-1 infection [7]. This is mostly due to the difficulty of performing amplification and sequencing analysis with limited volume of blood in perinatally HIV infected children on viral suppression since infancy [7–9]. Here, we reported the case of limited HIV-1 viral evolution in an early treated child with stable viral VL <40 copies/ml in which we were able to amplify and analyze HIV-1 pol sequences at different time points.\n\nCase report\nAn infant was born by elective caesarean section, two hours after membrane rupture at 38 weeks of gestation to an HIV-1 infected woman who started a first line ART with lamivudine, zidovudine and lopinavir/ritonavir 1 week before the delivery. Maternal VL at delivery was 203,686 copies/ml. Intrapartum antiretroviral prophylaxis with intravenous zidovudine was administered and the child started postnatal prophylaxis with zidovudine at 6 h of birth for 6 weeks. Breastfeeding was avoided. Polymerase chain reaction (PCR) for genes GAG, POL, and ENV performed at 6 weeks of life was positive and his HIV-RNA VL was >500,000 copies/mL with CD4 lymphocyte percentage 35%.\n\nThe genotypic resistance test from both mother and child didn’t show any transmitted drug resistance for PI, NRTI or NNRTI drug classes. Based on these results, at 7 weeks of age cART was initiated. A four-drug regimen of zidovudine, lamivudine, nevirapine and lopinavir/ritonavir was selected according to the results of genotypic resistance test. Plasma VL remained detectable till the 32th week from starting therapy despite an adequate maternal compliance with infant’s drugs and on subsequent medical check the baby maintained undetectable HIV-1 RNA and CD4 T count within the range for age. At 48 weeks from starting therapy, ART was simplified by suspending protease inhibitor. Concurrently to the VL undetectability, HIV-1 antibodies were negative in the child at 26, and 31 months of age. After 116 weeks on cART, we were able to perform viral isolation and amplification. At this time VL was stable <40 copies/ml (ABBOTT) and CD4 percentage was 40%. A genotypic resistance test for pol was re-performed and no-drug resistance was found for a second time.\n\nIn order to clarify the epidemiological linkage and the evolutionary divergence between mother and child HIV-1 strains, a phylogenetic analysis was carried out on pol sequences performed at different time points. In particular, one pol sequence from plasma HIV-RNA and one pol sequence from PBMCs HIV-1 DNA obtained at the time of partum and 2 years later, respectively, were available for the mother. Two plasma pol sequences at the time of birth and 2 years later (corresponding to the 116 week of ART), were available for the child. To define the HIV-1 subtype and the sequence inter-relationships between the mother/child pair a neighbor joining (NJ) tree [10] was constructed using a first dataset containing all pol sequences obtained from the mother and child, HIV pol reference sequences, and 396 full-length pol sequences (1,200 bp) obtained from routine laboratory testing at the Virology Unit Hospital “Tor Vergata”, from January 2012 to December 2014. The reliability of the branching orders was assessed by bootstrap analysis of 1000 replicates. Genetic distances were calculated using MEGA 6.0 based on Kimura-2 parameter (K2P) model [11]. To avoid potential contaminations identical sequences amplified in the same run were excluded. Phylogenetic analysis by NJ method revealed that the HIV-1 pol sequences from the mother/child pair clustered together with C subtype reference strains, forming a monophyletic cluster distinct from the other C sequences included in the analysis (bootstrap value >90%) (Additional file 1: Figure S1).\n\nOnce the HIV-1 subtype was assigned, the statistical robustness of the monophyletic clade was confirmed also by the ML tree, containing only C reference sequences and 98 C isolates obtained from routine laboratory testing (bootstrap value >85%) (Fig. 1). This was inferred by the PhyML program (http://www.atgc-montpellier.fr/phyml/) using the GTR + I + Γ nucleotide substitution model. The simplest model that adequately fitted the sequence data was selected according to the Akaike Information Criterion (AIC) included in the MEGA package (version 6.0). Robustness of the phylogenetic clades was evaluated by bootstrap analysis (1000 replicates). The tree was rooted using a midpoint rooting. Again, the 4 pol sequences from the mother/child pair form a monophyletic cluster distinct from all the other C sequences included in the analysis (Fig. 1).Fig. 1 Maximum likelihood phylogenetic tree constructed on the pol gene sequences of 102 isolates and additional 4 subtype C references. The tree was rooted using the midpoint rooting method. Branch lenghts were estimated with the best fitting nucleotide substitution model (GTR + G + I) according to a hierarchical likelihood ratio test. The bar at the bottom indicating 0.03 nucleotide substitution per site. The astericks (*) along a branch represent bootstrap support >85%. The 4 C sequences belonged to mother to child transmission chain are shown in red and the cluster involving them is in the gray box. The cartoon summarizes the timing of sampling\n\n\n\n\nThe extremely low mean genetic distance in pol region characterizing pol sequences from the mother/child pair compared to the ones from local unrelated non-cluster C controls (pol: 0.0017, standard error [SE]:±0.001 vs 0.081, standard error [SE]:±0.004) confirmed the high homology among mother and child sequences.\n\nThe phylogenetic analysis also revealed that the 2 sequences of the child clustered together and showed a minimal evolutionary divergence among them (mean ± SE:0.000090 ± 000087). This minimal evolutionary divergence is sustained by a single nucleotide substitution at position 231 of RT (C to T [F77F]).\n\nConclusions\nHIV-1 populations in the blood of the newly infected individuals are largely homogenous and evolve in a manner consistent with exponential viral replication [3]. Thus, starting antiretroviral treatment during acute infection can limit HIV viral evolution avoiding the emergence of new viral variants. Recent studies in HIV infected adults support this evidence [4–6] but few data are available in the pediatric setting [7]. The present case report highlights the impact of eART in limiting HIV genetic diversity over time in a perinatally HIV infected child on stable viral suppression (<40 copies/ml). Our result confirming those recently published in adults [4–6], may have important implications for the future defining of a personalized immunotherapeutic approach [12]. To date, eART alone is not sufficient to induce a sustained viral remission and additional immunotherapeutic interventions should be considered [12]. An effective early cART can prevent HIV-1 evolution modifying the natural history of the infection from a rapidly evolving viral infection to a state of clonal persistence with a single or a few variants. This restricted pool of variants can be more easily targeted by autologous cytotoxic T-lymphocytes (CTL) [13] or therapeutic vaccines induced strategies [12, 14]. Further studies are needed in order to determine whether limited HIV-1 evolution overtime can be associated with a higher likelihood to achieve viral remission [9].\n\nAdditional files\n\nAdditional file 1: Figure S1. Neighborg phylogenetic tree constructed on the pol gene sequences of 400 isolates and additional 163 HIV-1 subtype references. The bar at the bottom indicating 0.01 nucleotide substitution per site. Bootstrap support >90% were showed along the branches. Isolates of sutypes C are shown in red. The sequences involved in mother to child transmission chain are in bold red. (PPTX 160 kb).\n\n\n\n\nAbbreviations\nARTAntiretroviral treatment\n\ncARTCombination antiretroviral therapy\n\nCTLCytotoxic T-lymphocytes\n\neARTEarly antiretroviral treatment\n\nNJNeighbor joining\n\nPCRPolymerase chain reaction\n\nVLViral load\n\nWe would like to acknowledge the patient and his mother who participated in this study.\n\nFunding\nThis work was supported by research projects funding of Italian Ministry of Health (grant number: 201201X002919).\n\nAvailability of data and materials\nThe datasets supporting the conclusions of this article are included within the article.\n\nAuthors’ contributions\nSB, HT, PP, GL, ECM carried out the clinical follow up. PZ, SB, CA, AB, PP draft the manuscript. CA and AB performed laboratory analysis. PR supervised the clinical follow up. CFP supervised laboratory and phylogenetic analysis. All authors read and approved the final manuscript.\n\nCompeting interests\nThe authors declare that they have no competing interests.\n\nConsent for publication\nWritten informed consent was obtained from the patient’s mother for publication of this report. A copy of the written consent is available for the journal.\n\nEthics approval and consent to participate\nNot applicable.\n==== Refs\nReferences\n1. Santoro MM Perno CF HIV-1 Genetic Variability and Clinical Implications ISRN Microbiol 2013 2013 481314 10.1155/2013/481314 23844315 \n2. Scarlatti G Leitner T Halapi E Wahlberg J Jansson M Wigzell H Analysis of the HIV-1 envelope V3-loop sequences from ten mother-child pairs Ann N Y Acad Sci 1993 693 277 280 10.1111/j.1749-6632.1993.tb26282.x 8267278 \n3. Joseph SB Swanstrom R Kashuba AD Cohen MS Bottlenecks in HIV-1 transmission: insights from the study of founder viruses Nat Rev Microbiol 2015 13 7 414 25 10.1038/nrmicro3471 26052661 \n4. Josefsson L von Stockenstrom S Faria NR Sinclair E Bacchetti P Killian M The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over tiime PNAS 2013 110 51 4987 96 10.1073/pnas.1308313110 \n5. Buzon MJ Sun H Li C Shaw A Seiss K Ouyang Z HIV-1 persistence in CD4+ T cells with stem cell-like properties Nat Med 2014 20 2 139 42 10.1038/nm.3445 24412925 \n6. Kearney MF Spindler J Shao W Yu S Anderson EM O’Shea A Lack of detectable HIV-1 molecular evolution during suppressive antiretroviral therapy PLoS Pathog 2014 10 3 e1004010 10.1371/journal.ppat.1004010 24651464 \n7. Persaud D Ray SC Kajdas J Ahonkhai A Siberry GK Ferguson K Slow human immunodeficiency virus type 1 evolution in viral reservoirs in infants treated with effective antiretroviral therapy AIDS Res Hum Retroviruses 2007 23 3 381 90 10.1089/aid.2006.0175 17411371 \n8. Luzuriaga K Mofenson LM Challenges in the Elimination of Pediatric HIV-1 Infection N Engl J Med 2016 374 8 761 70 10.1056/NEJMra1505256 26933850 \n9. Palma P Foster C Rojo P Zangari P Yates A Cotugno N Klein N The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children J Virus Erad 2015 1 3 134 139 26893908 \n10. Saitou N Nei M The neighbor-joining method: a new method for reconstructing phylogenetic trees Mol Biol Evol 1987 4 4 406 25 3447015 \n11. Kimura M A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences J Mol Evol 1980 16 111 120 10.1007/BF01731581 7463489 \n12. Klein N Palma P Luzuriaga K Pahwa S Nastouli E Gibb DM Early antiretroviral therapy in children perinatally infected with HIV: a unique opportunity to implement immunotherapeutic approaches to prolong viral remission Lancet Infect Dis 2015 15 9 1108 14 10.1016/S1473-3099(15)00052-3 26187030 \n13. Garcia-Knight MA Slyker J Lohman-Payne B Pond SL de Silva TI Chohan B Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection Sci Rep 2016 6 29536 10.1038/srep29536 27403940 \n14. Goulder PJ Lewin SR Leitman EM Paediatric HIV infection: the potential for cure Nat Rev Immunol 2016 16 4 259 71 10.1038/nri.2016.19 26972723\n\n", "fulltext_license": "CC BY", "issn_linking": "1471-2334", "issue": "16(1)", "journal": "BMC infectious diseases", "keywords": "Children; Early antiretroviral treatment; HIV; Immunotherapy; Viral evolution", "medline_ta": "BMC Infect Dis", "mesh_terms": "D019380:Anti-HIV Agents; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019259:Lamivudine; D061466:Lopinavir; D008297:Male; D019829:Nevirapine; D010802:Phylogeny; D019438:Ritonavir; D015215:Zidovudine", "nlm_unique_id": "100968551", "other_id": null, "pages": "742", "pmc": null, "pmid": "27938348", "pubdate": "2016-12-09", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "17411371;26052661;8267278;3447015;26933850;26893908;24651464;27403940;24277811;23844315;7463489;26972723;24412925;26187030", "title": "Early antiretroviral treatment (eART) limits viral diversity over time in a long-term HIV viral suppressed perinatally infected child.", "title_normalized": "early antiretroviral treatment eart limits viral diversity over time in a long term hiv viral suppressed perinatally infected child" }

[ { "companynumb": "IT-VIIV HEALTHCARE LIMITED-IT2017GSK030994", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": "020564", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LOPINAVIR\\RITONAVIR" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOPINAVIR+RITONAVIR" } ], "patientagegroup": "1", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Live birth", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Foetal exposure during pregnancy", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Perinatal HIV infection", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PALMA P, ZANGARI P, ALTERI C, TCHIDJOUI HK, MANNO EC, LIUZZI G ET AL. EARLY ANTIRETROVIRAL TREATMENT (EART) LIMITS VIRAL DIVERSITY OVER TIME IN A LONG-TERM HIV VIRAL SUPPRESSED PERINATALLY INFECTED CHILD. BMC INFECTIOUS DISEASES. 2016;16:742", "literaturereference_normalized": "early antiretroviral treatment eart limits viral diversity over time in a long term hiv viral suppressed perinatally infected child", "qualification": "1", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20170308", "receivedate": "20170308", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13305214, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20170428" }, { "companynumb": "IT-GLAXOSMITHKLINE-IT2017GSK030994", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "ZIDOVUDINE" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZIDOVUDINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LOPINAVIR\\RITONAVIR" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOPINAVIR+RITONAVIR" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LAMIVUDINE" }, "drugadditional": null, "drugadministrationroute": "064", "drugauthorizationnumb": "020564", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "HIV INFECTION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAMIVUDINE." } ], "patientagegroup": "1", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Live birth", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Perinatal HIV infection", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Foetal exposure during pregnancy", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PALMA P, ZANGARI P, ALTERI C, TCHIDJOUI HK, MANNO EC, LIUZZI G ET AL. EARLY ANTIRETROVIRAL TREATMENT (EART) LIMITS VIRAL DIVERSITY OVER TIME IN A LONG-TERM HIV VIRAL SUPPRESSED PERINATALLY INFECTED CHILD. BMC INFECTIOUS DISEASES. 2016;16:742", "literaturereference_normalized": "early antiretroviral treatment eart limits viral diversity over time in a long term hiv viral suppressed perinatally infected child", "qualification": "1", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20170308", "receivedate": "20170308", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13305502, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20170428" } ]

{ "abstract": "Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an intractable, though rare, complication in cancer patients with bone metastases and patients with osteoporosis who are treated with antiresorptive agents, including bisphosphonates and denosumab. Despite the more than 10 years that have passed since the first cases of bisphosphonate-related osteonecrosis of the jaw (BRONJ) were reported, our understanding of the epidemiology and pathophysiology of ARONJ remains limited, and data supported by evidence-based medicine are still sparse. However, the diagnosis and staging of ARONJ, identification of risk factors, and development of preventive and therapeutic approaches have advanced significantly over the past decade. The Position Paper 2017 is an updated version of the Position Paper 2010 of the Japanese Allied Committee on Osteonecrosis of the Jaw, which now comprises six Japanese academic societies. The Position Paper 2017 describes a new diagnostic definition for ARONJ, as proposed by the American Association of Oral and Maxillofacial Surgeons (AAOMS), summarizes our current understanding of the pathophysiology of ARONJ based on a literature search, and suggests methods for physicians and dentists/oral surgeons to manage the disease. In addition, the appropriateness of discontinuing antiresorptive medications (drug holiday) before, during, and after invasive dental treatments is discussed extensively. More importantly, the manuscript also proposes, for the first time, the importance of interactive communication and cooperation between physicians and dentists/oral surgeons for the successful treatment of ARONJ. The Position Paper 2017 is intended to serve as a guide for improving the management of ARONJ patients in Japan.", "affiliations": "Division of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, USA. toshyone@iu.edu.;School of Health Science, Faculty of Medicine, Tottori University, Tottori, Japan.;Internal Medicine 1, Shimane University Faculty of Medicine, Matsue, Japan.;Clinical Research Centers for Medicine, International University of Health and Welfare, Ohtawara, Japan.;Department of Medical Oncology, The Cancer Institute Hospital Of Japanese Foundation of Cancer Research, Tokyo, Japan.;Department of Orthopaedic Surgery and Rheumatology, Kindai University Nara Hospital, Ikoma, Japan.;Department of Hard Tissue Research, Graduate School of Oral Medicine, Matsumoto Dental University, Shiojiri, Japan.;Department of Periodontology and Endodontology, School of Dentistry, Tokushima University, Tokushima, Japan.;Department of Oral and Maxillofacial Surgery, Hyogo College of Medicine, Nishinomiya, Japan.;Department of Oral and Maxillo-Facial Surgery, Tokyo Dental College, Tokyo, Japan.;Department of Oral Pathology, Osaka University Graduate School of Dentistry, Suita, Japan.", "authors": "|||;Yoneda|Toshiyuki|T|;Hagino|Hiroshi|H|;Sugimoto|Toshitsugu|T|;Ohta|Hiroaki|H|;Takahashi|Shunji|S|;Soen|Satoshi|S|;Taguchi|Akira|A|;Nagata|Toshihiko|T|;Urade|Masahiro|M|;Shibahara|Takahiko|T|;Toyosawa|Satoru|S|", "chemical_list": null, "country": "Japan", "delete": false, "doi": "10.1007/s00774-016-0810-7", "fulltext": null, "fulltext_license": null, "issn_linking": "0914-8779", "issue": "35(1)", "journal": "Journal of bone and mineral metabolism", "keywords": "Bisphosphonates; Denosumab; Drug holidays; Oral bacterial infection; Osteonecrosis of the jaw; Team therapeutic approaches", "medline_ta": "J Bone Miner Metab", "mesh_terms": "D044466:Asians; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D010506:Periodicals as Topic; D017410:Practice Guidelines as Topic", "nlm_unique_id": "9436705", "other_id": null, "pages": "6-19", "pmc": null, "pmid": "28035494", "pubdate": "2017-01", "publication_types": "D016428:Journal Article; D016454:Review", "references": "26789873;26493811;25148238;21782307;25956267;23071071;27007294;25639776;19450715;18940358;26924135;21986094;24664275;22065238;22975218;24115073;26008732;25234529;25727550;24490612;18483689;26210799;24880820;26795450;19118304;25414052;25403903;22041409;26232916;20851366;25511956;21317246;26277349;25549869;24758181;26304604;23246226;18022461;26893859;25646168;26713306;25958767;21145999;26116306;24480762;25884045;27142558;26001561;25089126;25234534;20333419;12966493", "title": "Antiresorptive agent-related osteonecrosis of the jaw: Position Paper 2017 of the Japanese Allied Committee on Osteonecrosis of the Jaw.", "title_normalized": "antiresorptive agent related osteonecrosis of the jaw position paper 2017 of the japanese allied committee on osteonecrosis of the jaw" }

[ { "companynumb": "JP-AMGEN-JPNSP2017012097", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "DENOSUMAB" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "125320", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK, 16 TIMES", "drugenddate": "20131112", "drugenddateformat": "102", "drugindication": "METASTASES TO BONE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20120812", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RANMARK" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "FULVESTRANT" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "METASTASES TO BONE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FASLODEX" } ], "patientagegroup": "6", "patientonsetage": "73", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Osteonecrosis of jaw", "reactionmeddraversionpt": "19.1", "reactionoutcome": "4" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 201302" } }, "primarysource": { "literaturereference": "YONEDA T, HAGINO H, SUGIMOTO T, ET AL.. ANTIRESORPTIVE AGENT-RELATED OSTEONECROSIS OF THE JAW: POSITION PAPER 2017 OF THE JAPANESE ALLIED COMMITTEE ON OSTEONECROSIS OF THE JAW.. J. BONE MINER METAB.. 2017", "literaturereference_normalized": "antiresorptive agent related osteonecrosis of the jaw position paper 2017 of the japanese allied committee on osteonecrosis of the jaw", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20170326", "receivedate": "20170124", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13145998, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": 1, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20170428" }, { "companynumb": "JP-AMGEN-JPNSP2017012113", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DECADRON" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ZOLEDRONIC ACID" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": "201203", "drugenddateformat": "610", "drugindication": "METASTASES TO BONE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "200911", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ZOMETA" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DENOSUMAB" }, "drugadditional": "2", "drugadministrationroute": "065", "drugauthorizationnumb": "125320", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "UNK, 13TIME", "drugenddate": "201304", "drugenddateformat": "610", "drugindication": "METASTASES TO BONE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201204", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RANMARK" } ], "patientagegroup": "6", "patientonsetage": "68", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Osteonecrosis of jaw", "reactionmeddraversionpt": "19.1", "reactionoutcome": "3" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 201302" } }, "primarysource": { "literaturereference": "YONEDA T, HAGINO H, SUGIMOTO T, ET AL. ANTIRESORPTIVE AGENT-RELATED OSTEONECROSIS OF THE JAW: POSITION PAPER 2017 OF THE JAPANESE ALLIED COMMITTEE ON OSTEONECROSIS OF THE JAW.. J BONE MINER METAB. 2017", "literaturereference_normalized": "antiresorptive agent related osteonecrosis of the jaw position paper 2017 of the japanese allied committee on osteonecrosis of the jaw", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20170326", "receivedate": "20170125", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13152659, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": 1, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20170428" } ]

{ "abstract": "Biologics have been used to treat refractory Takayasu arteritis (TAK), but their efficacy and safety have not been sufficiently evaluated.\nWe extracted clinical information from medical records for TAK patients who were treated with biologics including ustekinumab (UST) at Kyoto University Hospital. We also analysed the patient's genetic backgrounds.\nOf 163 cases, 12 (7.4%) were treated with infliximab, tocilizumab, or UST (n = 3). Erythrocyte sedimentation rate (ESR), C-reactive protein levels (CRP), and prednisolone (PSL) dose were significantly decreased 12 months after the initiation of biologics. When compared with the 15 patients who were only treated with immunosuppressants (IS group), the change in ESR from baseline was significantly lower in the biologics group than in the IS group (-2 mm/h, p = .005). The proportion of patients with HLA-B*52 and the risk-type alleles of the SNP were similar in both groups. Among the biologics, TCZ showed the highest continuation rate. UST exhibited marginal effects on reducing ESR, CRP levels, and PSL dose. No adverse events were observed in patients with UST for approximately 3 years.\nBiological treatments resulted in a reduction in inflammatory markers and PSL dose in refractory TAK patients.", "affiliations": "Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.;Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.;Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.;Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.;Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.;Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.;Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.;Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.", "authors": "Gon|Yoshie|Y|;Yoshifuji|Hajime|H|;Nakajima|Toshiki|T|;Murakami|Kosaku|K|;Nakashima|Ran|R|;Ohmura|Koichiro|K|;Mimori|Tsuneyo|T|;Terao|Chikashi|C|", "chemical_list": "D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; D007166:Immunosuppressive Agents; D000069285:Infliximab; D000069549:Ustekinumab; C502936:tocilizumab", "country": "England", "delete": false, "doi": "10.1080/14397595.2020.1800560", "fulltext": null, "fulltext_license": null, "issn_linking": "1439-7595", "issue": "31(3)", "journal": "Modern rheumatology", "keywords": "IL-12; Takayasu arteritis; infliximab; tocilizumab; ustekinumab", "medline_ta": "Mod Rheumatol", "mesh_terms": "D000328:Adult; D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; D001799:Blood Sedimentation; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D013625:Takayasu Arteritis; D016896:Treatment Outcome; D000069549:Ustekinumab", "nlm_unique_id": "100959226", "other_id": null, "pages": "678-683", "pmc": null, "pmid": "32700985", "pubdate": "2021-05", "publication_types": "D016428:Journal Article", "references": null, "title": "Long-term outcomes of refractory Takayasu arteritis patients treated with biologics including ustekinumab.", "title_normalized": "long term outcomes of refractory takayasu arteritis patients treated with biologics including ustekinumab" }

[ { "companynumb": "JP-JNJFOC-20180409004", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "INFLIXIMAB" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "103772", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INFUSION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "TAKAYASU^S ARTERITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "REMICADE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Breast cancer", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GON Y, YOSHIFUJI H, NAKAJIMA T, MURAKAMI K, NAKASHIMA R, OHMURA K, MIMORI T, TERAO C. LONG?TERM OUTCOMES OF REFRACTORY TAKAYASU ARTERITIS PATIENTS TREATED WITH BIOLOGICS INCLUDING USTEKINUMAB. MODERN RHEUMATOLOGY. 2020?.", "literaturereference_normalized": "long term outcomes of refractory takayasu arteritis patients treated with biologics including ustekinumab", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20200807", "receivedate": "20180412", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14752885, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201102" }, { "companynumb": "JP-ROCHE-2850161", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "TOCILIZUMAB" }, "drugadditional": null, "drugadministrationroute": "041", "drugauthorizationnumb": "125276", "drugbatchnumb": "ASKED BUT UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "TAKAYASU^S ARTERITIS", "drugintervaldosagedefinition": "802", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TOCILIZUMAB." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "TAKAYASU^S ARTERITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cardiac failure chronic", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GON Y, YOSHIFUJI H, NAKAJIMA T, MURAKAMI K, NAKASHIMA R, OHMURA K, MIMORI T AND TERAO C. LONG?TERM OUTCOMES OF REFRACTORY TAKAYASU ARTERITIS PATIENTS TREATED WITH BIOLOGICS INCLUDING USTEKINUMAB. MODERN RHEUMATOLOGY 2021?31 (3):678?83.", "literaturereference_normalized": "long term outcomes of refractory takayasu arteritis patients treated with biologics including ustekinumab", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20210625", "receivedate": "20210615", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 19419543, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210717" } ]

{ "abstract": "Major Histocompatibility Complex (MHC) class II (MHCII) deficiency (MHCII-D), also known as Bare Lymphocyte Syndrome (BLS), is a rare combined immunodeficiency due to mutations in genes regulating expression of MHCII molecules. MHCII deficiency results in impaired cellular and humoral immune responses, leading to severe infections and autoimmunity. Abnormal cross-talk with developing T cells due to the absence of MHCII expression likely leads to defects in thymic epithelial cells (TEC). However, the contribution of TEC alterations to the pathogenesis of this primary immunodeficiency has not been well characterized to date, in particular in regard to immune dysregulation. To this aim, we have performed an in-depth cellular and molecular characterization of TEC in this disease. We observed an overall perturbation of thymic structure and function in both MHCII-/- mice and patients. Transcriptomic and proteomic profiling of murine TEC revealed several alterations. In particular, we demonstrated that impairment of lymphostromal cross-talk in the thymus of MHCII-/- mice affects mTEC maturation and promiscuous gene expression and causes defects of central tolerance. Furthermore, we observed peripheral tolerance impairment, likely due to defective Treg cell generation and/or function and B cell tolerance breakdown. Overall, our findings reveal disease-specific TEC defects resulting in perturbation of central tolerance and limiting the potential benefits of hematopoietic stem cell transplantation in MHCII deficiency.", "affiliations": "San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.;San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.;Human Genome Department, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.;Department of Biomedical Sciences, Institute for Biomedical Technologies-National Research Council (CNR), Milan, Italy.;Human Genome Department, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.;San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.;San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.;Department of Biomedical Sciences, Institute for Biomedical Technologies-National Research Council (CNR), Milan, Italy.;San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.;Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.;Department of Pediatric Immunology, Hematology and Rheumatology, Necker Children's Hospital, AP-HP, Paris, France.;Department of Pediatric Immunology, Hematology and Rheumatology, Necker Children's Hospital, AP-HP, Paris, France.;Department of Diagnostic Sciences, Ghent University Hospital, Ghent University, Ghent, Belgium.;Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.;Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.;Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.;Cytogenetics and Medical Genetics Unit and \"A. Nocivelli\" Institute for Molecular Medicine, Spedali Civili Hospital, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.;Unit of Pediatric Immunology, Pediatrics Clinic, University of Brescia, ASST-Spedali Civili Brescia, Brescia, Italy.;Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.;Department of Pediatric Immunology and HSCT, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.;Division of Blood and Marrow Transplantation, Children's National Hospital, Washington, DC, United States.;Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, United States.;Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, United States.;Division of Immunology & Allergy, Department of Pediatrics, The Hospital for Sick Children, the Canadian Centre for Primary Immunodeficiency and the University of Toronto, Toronto, ON, Canada.;Department of Molecular and Translational Medicine, Pathology Unit, University of Brescia, Brescia, Italy.;CRS4, Science and Technology Park Polaris, Pula, Cagliari, Italy.;Department of Biomedical Sciences, Institute for Biomedical Technologies-National Research Council (CNR), Milan, Italy.;San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.;San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.", "authors": "Ferrua|Francesca|F|;Bortolomai|Ileana|I|;Fontana|Elena|E|;Di Silvestre|Dario|D|;Rigoni|Rosita|R|;Marcovecchio|Genni Enza|GE|;Draghici|Elena|E|;Brambilla|Francesca|F|;Castiello|Maria Carmina|MC|;Delfanti|Gloria|G|;Moshous|Despina|D|;Picard|Capucine|C|;Taghon|Tom|T|;Bordon|Victoria|V|;Schulz|Ansgar S|AS|;Schuetz|Catharina|C|;Giliani|Silvia|S|;Soresina|Annarosa|A|;Gennery|Andrew R|AR|;Signa|Sara|S|;Dávila Saldaña|Blachy J|BJ|;Delmonte|Ottavia M|OM|;Notarangelo|Luigi D|LD|;Roifman|Chaim M|CM|;Poliani|Pietro Luigi|PL|;Uva|Paolo|P|;Mauri|Pier Luigi|PL|;Villa|Anna|A|;Bosticardo|Marita|M|", "chemical_list": "D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D020543:Proteome; C064658:RAG-1 protein", "country": "Switzerland", "delete": false, "doi": "10.3389/fimmu.2021.669943", "fulltext": "\n==== Front\nFront Immunol\nFront Immunol\nFront. Immunol.\nFrontiers in Immunology\n1664-3224\nFrontiers Media S.A.\n\n10.3389/fimmu.2021.669943\nImmunology\nOriginal Research\nThymic Epithelial Cell Alterations and Defective Thymopoiesis Lead to Central and Peripheral Tolerance Perturbation in MHCII Deficiency\nFerrua Francesca 1 2 3\n\nBortolomai Ileana 1\n\nFontana Elena 4 5\n\nDi Silvestre Dario 6\n\nRigoni Rosita 4 5\nMarcovecchio Genni Enza 1\n\nDraghici Elena 1\nBrambilla Francesca 6\nCastiello Maria Carmina 1 5\n\nDelfanti Gloria 7\nMoshous Despina 8 9\n\nPicard Capucine 8 10 11\n\nTaghon Tom 12\n\nBordon Victoria 13\n\nSchulz Ansgar S. 14\n\nSchuetz Catharina 14 15\n\nGiliani Silvia 16\n\nSoresina Annarosa 17\n\nGennery Andrew R. 18 19\n\nSigna Sara 19 20\n\nDávila Saldaña Blachy J. 21\n\nDelmonte Ottavia M. 22\n\nNotarangelo Luigi D. 22\n\nRoifman Chaim M. 23\n\nPoliani Pietro Luigi 24\n\nUva Paolo 25\n\nMauri Pier Luigi 6\n\nVilla Anna 1 5 †\n\nBosticardo Marita 1 22 * †\n\n1 San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy\n2 Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy\n3 Vita-Salute San Raffaele University, Milan, Italy\n4 Human Genome Department, Humanitas Clinical and Research Center, Rozzano, Milan, Italy\n5 Milan Unit, Institute of Genetic and Biomedical Research, National Research Council (CNR), Milan, Italy\n6 Department of Biomedical Sciences, Institute for Biomedical Technologies-National Research Council (CNR), Milan, Italy\n7 Experimental Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy\n8 Department of Pediatric Immunology, Hematology and Rheumatology, Necker Children’s Hospital, AP-HP, Paris, France\n9 Laboratory “Genome Dynamics in the Immune System”, INSERM UMR1163, Université de Paris, Institut Imagine, Paris, France\n10 Centre d’Etude des Déficits Immunitaires, Necker-Enfants Malades Hospital, AP-HP, Paris, France\n11 Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Inserm UMR 1163, University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France\n12 Department of Diagnostic Sciences, Ghent University Hospital, Ghent University, Ghent, Belgium\n13 Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium\n14 Department of Pediatrics, University Medical Center Ulm, Ulm, Germany\n15 Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany\n16 Cytogenetics and Medical Genetics Unit and “A. Nocivelli” Institute for Molecular Medicine, Spedali Civili Hospital, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy\n17 Unit of Pediatric Immunology, Pediatrics Clinic, University of Brescia, ASST-Spedali Civili Brescia, Brescia, Italy\n18 Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom\n19 Department of Pediatric Immunology and HSCT, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom\n20 Autoinflammatory Diseases and Immunodeficiencies Center, IRCCS Istituto G. Gaslini, and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Children's Sciences, University of Genoa, Genoa, Italy\n21 Division of Blood and Marrow Transplantation, Children's National Hospital, Washington, DC, United States\n22 Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, United States\n23 Division of Immunology & Allergy, Department of Pediatrics, The Hospital for Sick Children, the Canadian Centre for Primary Immunodeficiency and the University of Toronto, Toronto, ON, Canada\n24 Department of Molecular and Translational Medicine, Pathology Unit, University of Brescia, Brescia, Italy\n25 CRS4, Science and Technology Park Polaris, Pula, Cagliari, Italy\nEdited by: Michele Kay Anderson, University of Toronto, Canada\n\nReviewed by: Magali Irla, INSERM U1104 Centre d'immunologie de Marseille-Luminy (CIML), France; Graham Anderson, University of Birmingham, United Kingdom\n\n*Correspondence: Marita Bosticardo, marita.bosticardo@nih.gov\n†These authors have contributed equally to this work\n\nThis article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology\n\n15 6 2021\n2021\n12 66994319 2 2021\n07 5 2021\nCopyright © 2021 Ferrua, Bortolomai, Fontana, Di Silvestre, Rigoni, Marcovecchio, Draghici, Brambilla, Castiello, Delfanti, Moshous, Picard, Taghon, Bordon, Schulz, Schuetz, Giliani, Soresina, Gennery, Signa, Dávila Saldaña, Delmonte, Notarangelo, Roifman, Poliani, Uva, Mauri, Villa and Bosticardo\n2021\nFerrua, Bortolomai, Fontana, Di Silvestre, Rigoni, Marcovecchio, Draghici, Brambilla, Castiello, Delfanti, Moshous, Picard, Taghon, Bordon, Schulz, Schuetz, Giliani, Soresina, Gennery, Signa, Dávila Saldaña, Delmonte, Notarangelo, Roifman, Poliani, Uva, Mauri, Villa and Bosticardo\nhttps://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.\nMajor Histocompatibility Complex (MHC) class II (MHCII) deficiency (MHCII-D), also known as Bare Lymphocyte Syndrome (BLS), is a rare combined immunodeficiency due to mutations in genes regulating expression of MHCII molecules. MHCII deficiency results in impaired cellular and humoral immune responses, leading to severe infections and autoimmunity. Abnormal cross-talk with developing T cells due to the absence of MHCII expression likely leads to defects in thymic epithelial cells (TEC). However, the contribution of TEC alterations to the pathogenesis of this primary immunodeficiency has not been well characterized to date, in particular in regard to immune dysregulation. To this aim, we have performed an in-depth cellular and molecular characterization of TEC in this disease. We observed an overall perturbation of thymic structure and function in both MHCII−/− mice and patients. Transcriptomic and proteomic profiling of murine TEC revealed several alterations. In particular, we demonstrated that impairment of lymphostromal cross-talk in the thymus of MHCII−/− mice affects mTEC maturation and promiscuous gene expression and causes defects of central tolerance. Furthermore, we observed peripheral tolerance impairment, likely due to defective Treg cell generation and/or function and B cell tolerance breakdown. Overall, our findings reveal disease-specific TEC defects resulting in perturbation of central tolerance and limiting the potential benefits of hematopoietic stem cell transplantation in MHCII deficiency.\n\nthymus\nthymic epithelial cells\nprimary immunodeficiency\nMHCII\ncentral tolerance\n==== Body\nIntroduction\n\nMajor Histocompatibility Complex (MHC) class II (MHCII) deficiency (MHCII-D), also known as Bare Lymphocyte Syndrome (BLS), is a rare autosomal recessive combined immunodeficiency (CID) due to mutations in genes regulating expression of MHCII molecules [OMIM#209920] (CIITA, RFXANK, RFX5, RFXAP) (1–4). MHCII molecules play a crucial role in immune responses, due to their fundamental role in presenting exogenous peptides to the antigen T-cell receptor (TCR) of CD4+ T lymphocytes. In the thymus, complexes formed by self-peptides and MHCII, expressed on thymic epithelial cells (TEC) and dendritic cells, drive the positive and negative selection processes, which are critical for the development of CD4+ T cells and the establishment of a non-self-reactive TCR repertoire (1, 4). In the periphery, MHCII molecules contribute to the induction of antigen-specific immune responses against pathogens and tumors and, through the presentation of self-peptides, to the maintenance of peripheral T-cell tolerance.\n\nDefects of antigen processing and presentation via MHCII molecules in patients with MHCII deficiency lead to impairment of thymic education and peripheral T-cell help (5, 6). Thymopoiesis is defective in this disease, presumably due to impaired thymic selection in the absence of MHCII on TEC (4, 7). Examination of thymic biopsies from two patients with CID and defective expression of MHC I and II molecules revealed normal lobular thymic architecture, with distinct cortex-medullary areas, well-differentiated epithelium, and presence of Hassall’s corpuscles. However, MHCII antigen expression was not detectable on epithelial cells in the cortex and absent/reduced in the medulla, in contrast to what was observed in normal controls (8). Study of thymic function in 8 MHCII-deficient patients (7) showed that, despite normal TCR-Vβ repertoire of total CD3+ T cells, clonal abnormalities emerged at flow cytometric evaluation of TCR-Vβ repertoire on CD4+ T cells and at spectratyping evaluation of TCR-Vγ repertoire on total CD3+ lymphocytes (7). These findings suggest a reduced global thymic activity in MHCII deficiency and emphasize the key role of MHCII molecules in the process of normal thymic maturation of T lymphocytes. However, interestingly, TCR excision circles (TREC) were detectable in patients’ total lymphocytes and sorted CD4+ cells, reflecting normal early T-cell development (4, 7).\n\nIn MHCII-D patients, lack of MHCII molecules expression on the cell surface results in severe CD4+ T-cell lymphopenia and impaired antigen-specific cellular and humoral immune responses. Usually hematopoiesis is not affected, and most patients have normal numbers of circulating B and total T cells. Despite intact response to mitogen stimulation, T-cell mediated responses to foreign antigens are impaired. Hypogammaglobulinemia is a common finding (1, 4) and antibody responses to immunizations and to infections by microbial agents are generally absent or markedly reduced (6). On the other hand, autoantibodies have been demonstrated in several patients (6) and autoimmune manifestations, such as autoimmune cytopenias, have been observed in 6–20% of patients (4, 9, 10). Patients suffer from recurrent and severe infections (viral, bacterial, fungal, and protozoan), primarily involving the respiratory and gastrointestinal tract (4, 11) since early in life. Inflammatory enteropathy is frequently observed and reflects the multifaceted disturbance of intestinal epithelial cell regulation of adaptive mucosal immunity due to the lack of MHCII expression on enterocytes (12). If untreated, MHCII deficiency is often fatal early in life (3, 4). Allogeneic hematopoietic stem cell transplantation (HSCT), preferably from an HLA-identical sibling donor, is the treatment of choice, but overall success rate is limited (10, 13–15). In recent years HSCT survival has improved, but CD4+ T-cell lymphopenia may persist (16).\n\nThe Aβ0/0 mouse model, lacking MHC class II antigens, shares some phenotypical features with MHCII-D (17, 18). Aβ0/0 mice have barely detectable numbers of CD4+ T lymphocytes in secondary lymphoid organs, while in the thymus, immature CD4 single-positive (SP) thymocytes are present, indicating impairment of positive selection process, particularly in its initial stages, when TCR/MHC interactions are required (19). Interestingly, it has been shown that a large proportion of residual CD4+ T cells correspond to CD1-restricted natural killer T (NKT) cells in MHCII-deficient mice (20, 21). In vivo treatment of Aβ0/0 mice with anti-TCR antibody has been shown to restore the generation of circulating CD4+ T cells and to normalize the thymic medulla (22). A reduction of the medullary TEC (mTEC) compartment has been described also in another MHCII ko mouse model (Aα−/− mice) (23). Reduced number of mature mTECs and decreased expression of Aire and Aire-dependent and -independent tissue restricted antigens (TRA) have been detected in the thymus of Aα−/− mice (24). The demonstration of CD8+ T cell infiltrates in multiple organs of Aα−/− mice suggested defects of central tolerance and/or of regulatory T (Treg) cells (24). While CD4+ FoxP3+ Treg cells were not found in the thymus of Aα−/− mice, they were present in the periphery and seemed functional and efficient in mediating immune suppression (25). Furthermore, in experimentally induced colitis models, regulatory CD25+ double-positive (DP) T cells generated in MHCII ko mice (Aα−/− or Aβ0/0), probably arising from SP CD8+ T cells, have been demonstrated to control the colitogenic potential of CD25−CD4+ T cells (26). Indeed, CD8+ T cells constitutively expressing CD25 and bearing characteristics similar to regulatory CD4+CD25+ T cells have been also detected in the thymus of MHCII−/− mice (27).\n\nIn conclusion, it is currently unclear if TEC defects are responsible, at least in part, for the pathogenesis of MHCII deficiency. To better define this issue, here we report on thymic defects in both patients and in the Aβ0/0 mouse model of MHCII-D and describe how these alterations lead to peripheral immune dysregulation.\n\nMaterials and Methods\n\nHuman Samples\n\nA thymic biopsy was obtained from a 23-month-old infant with MHCII deficiency upon informed consent in accordance with the Research Ethics Board at The Hospital for Sick Children in Toronto (Canada). Patient’s data were compiled prospectively and retrospectively from medical records and entered into the Primary Immunodeficiency Registry and Tissue Bank (REB protocol no. 1000005598). The patient presented at 18 months of life with a history of recurrent respiratory tract infections, chronic diarrhea, and CMV hepatitis. She had a family history of MHCII deficiency and was found to be homozygous for a mutation in the CIITA gene. Immunological data are reported in Table 1 . The patient received a matched related HSCT, but engraftment was poor.\n\nTable 1 Immunological work-up of the MHCII-D patient who underwent thymic biopsy.\n\nTest\tResults\t\nProliferative response to mitogens\t\t\n –PHA\t40–50% of control\t\n –Response to specific Ag at day 6(PPD, VZV, CMV, HSV, Candida)\tNo\t\nSerum immunoglobulins\tNormal\t\nImmune phenotype\t\t\n CD3\t64% (3,184/μl)\t\n CD4\t7.1% (356/μl)\t\n CD8\t44% (2,241/μl)\t\n CD56\t3% (151/μl)\t\n CD19\t34% (1,713/μl)\t\nAbnormal results according to age-based reference ranges (28) are reported in bold.\n\nPHA, phytohemagglutinin; Ag, antigen; PPD, tuberculin-purified protein derivative; VZV, Varicella-Zoster virus; CMV, Cytomegalovirus; HSV, Herpes Simplex virus.\n\nA human thymic sample from a healthy control used for comparison was analyzed retrospectively in compliance with Declaration of Helsinki and policies approved by Ethics Board of Spedali Civili in Brescia. Specifically, for retrospective and exclusively observational study on archival material obtained for diagnostic purposes, patient consent was not needed (Delibera del Garante n. 52 del 24/7/2008 and DL 193/2003).\n\nBlood samples were collected from 11 patients with MHCII deficiency [peripheral mononuclear cells (PBMC), n = 4; serum or plasma, n = 9]. Each patient was attributed a numerical code (MHCII_xx). Questionnaires to gather patient’s relevant clinical data were sent to referring clinicians, who were responsible for the collection of informed consent for biological samples’ collection and anonymized biological sample/data sharing from their own patients, according to local research protocols, reviewed and approved by local ethics committees or institutional review board (IRB) [for NIH patient’s samples, protocols 18-I-0041 and 18-I-0128, approved by the NIH IRB]. Data about clinical history, immunological features and HSCT of this cohort of MHCII-D patients are reported in Tables 2 – 4 respectively.\n\nTable 2 MHCII-D patients’ features.\n\nPatient code\tMutated gene\tAge at sampling (years)\tPre/Post HSCT\tInfections\tImmune dysregulation\tChronic diarrhea\t\nMHCII_01\tNK\t0.5\tPre\tYes\tNo\tYes\t\nMHCII_02\tRFXANK\t12.8\tPre\tYes\tAIHA\tYes\t\nMHCII_03\tRFXANK\t0.9\tPre\tYes\tNo\tNo\t\nMHCII_04\tRFXANK\t4.0\tPre\tYes\tNo\tYes\t\nMHCII_05\tRFXAP\t16.0\tPre\tYes\tAutoimmune enteropathy and polyendocrinopathy#\tYes\t\nMHCII_08\tRFXANK\t6.5\tPost\n(+2 years)\tYes\tNo\tYes\t\nMHCII_09*\tRFXANK\t4.7\tPre\tYes\tNo\tYes\t\nMHCII_10*\tRFXANK\t4.6\tPre\tYes\tNo\tYes\t\nMHCII_11\tNK\t0.4\tPre\tYes\tNo\tNK\t\nMHCII_12\tRFXANK\t24.1\tPre\tYes\tNo\tYes\t\nMHCII_13\tRFXANK\t15.5\tPre\tYes\tAIHA, autoimmune thyroiditis, adrenal insufficiency\tNo\t\nNK, not known; HSCT, hematopoietic stem cell transplantation; AIHA, autoimmune hemolytic anemia; mo., months; Ab, antibody. #Insulin-dependent diabetes mellitus (IDDM) type 1, hypothyroidism.\n\n*These patients are described in greater detail in (16).\n\nTable 3 Immunophenotype and serum Ig level in our cohort of MHCII-D patients.\n\nPatient code\tCD3+ cells (×109/l)\tCD4+ cells (×109/l)\tCD8+ cells (×109/l)\tCD19+ cells (×109/l)\tCD16+/CD56+ cells (×109/l)\tHLA-DR+ cells (×109/l)\tIgM (g/L)\tIgG (g/L)\tIgA (g/L)\t\nMHCII_01\t1,495\t402\t1,087\t491\t30\tAbsent\t0.06\t4.94\t<0.02\t\nMHCII_02\t1,121\t240\t741\t261\t20\tAbsent\t0.31\t9.93\t<0.05\t\nMHCII_03\t1,021\t484\t480\t2,178\t77\t7\t0.29\t3.57\t0.2\t\nMHCII_04\tNA\tNA\tNA\tNA\tNA\tNA\tNA\tNA\tNA\t\nMHCII_05\tNA\tNA\tNA\tNA\tNA\tNA\tNA\tNA\tNA\t\nMHCII_08\t1,540\t901\t526\t1,315\t714\tPresent§\t1.17\t9.26\t<0.05\t\nMHCII_09*\t207\t71\t117\t58\t34\tAbsent\t0.27\t4.1°\t0.0\t\nMHCII_10*\t1,247\t535\t563\t243\t<16\tAbsent\t0.21\t18.2\t0.07\t\nMHCII_11\tNA\tNA\tNA\tNA\tNA\tNA\tNA\tNA\tNA\t\nMHCII_12\t725\t136\t444\t136\t45\t11 (tot. ly.),\n1 (B cells)\t0.004\t12.2\t0.006\t\nMHCII_13\t1,947\t331\t1,512\t62\t21\t41\t<0.13\t8.07\t<0.07\t\nData are reported at blood sampling. Abnormal results according to age-based reference ranges (28) are reported in bold.\n\n°Not on Ig replacement therapy at sampling. §Patient with 100% donor chimerism after HSCT. ND, not done; NK, not known; NA, not available; ly., lymphocytes.\n\n*These patients are described in greater detail in (16).\n\nTable 4 MHCII-D patients’ treatment features.\n\nPatient code\tHSCT\tAge at HSCT (years)\tDonor\tHSC source\tConditioning regimen\tComplications after HSCT\tDonor chimerism§\tHSCT outcome§\t\nMHCII_01\tYes°\t1.5\tMUD\tPBSC\tBu/Flu/\nATG\tGVHD, respiratory insufficiency\tNK\tDeceased\n(+1.8 mo. after HSCT)\t\nMHCII_02\tNo\t–\t–\t–\t–\t–\t–\t–\t\nMHCII_03\tYes°\t1.1\tMUD\tBM\tBu/Cy/\nATG\tNo\t31% T cells,\n8% B cells\tAlive and well\t\nMHCII_04\tYes°\t4.0\tMUD\tBM\tTreo/Flu/TT/\nAlemtuzumab\tMucositis, CLS, brain hemorrhage\tNK\tDeceased\n(+25 days after HSCT)\t\nMHCII_05\tYes°\t16.2\tMUD\tBM\tBu/Flu/TT/\nAlemtuzumab\tVOD, GVHD, infections, cytopenias\t100%\tDeceased\n(+5 mo. after HSCT)\t\nMHCII_08\tYes\t4.5\tMRD\tBM\tBu/Flu/\nATG\tGVHD, TMA\t100%\tAlive and well\n(but lung sequelae)\t\nMHCII_09*\tYes°\t5.2\tMUD\tPBSC\tTreo/Flu/\nAlemtuzumab\tViral infections\t100%\tAlive and well\t\nMHCII_10*\tYes°\t6.1\tTCRαβ/CD19- depleted Haplo\tPBSC\tTreo/Flu/TT/\nATG/Rtx\tGVHD, severe infections,\nBM failure\t100%\n(after T-cell add-back +\ntop up haplo tx)\tDeceased\n(+6.5 mo. after first HSCT)\t\nMHCII_11\tNo\t–\t–\t–\t–\t–\t–\tDeceased\t\nMHCII_12\tNo\t–\t–\t–\t–\t–\t–\t–\t\nMHCII_13\tNo\t–\t–\t–\t–\t–\t–\t–\t\nATG, anti-thymocyte globulin; BM, bone marrow; Bu, Busulfan; CLS, capillary leak syndrome; Cy, cyclophosphamide; Flu, fludarabine; GVHD, graft-versus-host disease; HSC, hematopoietic stem cell; mo., months; MRD, matched related donor; MUD, matched unrelated donor; NK, not known; PBSC, peripheral blood stem cells; Rtx, rituximab; TMA, thrombotic microangiopathy; Treo, Treosulfan; TT, thiotepa; VOD, veno-occlusive disease.\n\n°performed after sample sampling. §at last available follow up.\n\n*These patients are described in greater detail in (16).\n\nPeripheral blood (PB) from healthy controls (HD) was obtained in accordance with the 1964 Declaration of Helsinki and its subsequent amendments, under biological material collection protocols approved by the Institutional Ethical Committee of San Raffaele Hospital (Tiget07, Tiget09). Informed consent was signed directly by the subject or by parents or legal representatives in case of minors.\n\nMice\n\nAβ0/0 mice were kindly provided by Dr. Matteo Iannacone (San Raffaele Scientific Institute, Milan, Italy). Rag1 −/− mice were purchased from The Jackson Laboratories. C57/black (BL) 6 control wild-type (WT) mice were purchased from Charles River Laboratories Inc. All mice were housed in specific pathogen-free conditions and treated according to protocols approved by the Animal Care and Use Committee of the San Raffaele Scientific Institute (Institutional Animal Care and Use Committee protocol no. 710 and 712).\n\nHistological Analysis\n\nFollowing sacrifice, thymus and gut tissue isolated from mice were formalin-fixed and paraffin-embedded. Hematoxylin and Eosin (H&E) staining was used to assay basic histopathological changes. Paraffin sections were de-waxed, rehydrated, endogenous peroxidase activity was blocked by 0.1% H2O2, and nonspecific background reduced with Rodent Block M (Biocare Medical, Concord, CA, USA) before heat-based antigen-retrieval treatment and incubation with antibodies. Depending on the primary antibodies used, sections were incubated with Rat-on-Mouse HRP-Polymer (Biocare Medical) or MACH 1™ Universal HRP Polymer Kit (Biocare Medical) or 4plus Streptavidin HRP label (Biocare Medical); reactions were developed in Biocare's Betazoid DAB and nuclei counterstained with Hematoxylin. Digital images were acquired with an Olympus XC50 camera mounted on a BX51 microscope (Olympus, Tokyo, Japan), with CellF Imaging software (Soft Imaging System GmbH, Münster, Germany) or with a Nikon Eclipse E600 Microscope (Nikon) with NIS Elements Software (Nikon). The following primary antibodies were used on thymic sections: rabbit anti-cytokeratin 5 (CK5) (1:200; Covance), rat anti-cytokeratin 8 (CK8) (1:200; Developmental Studies Hybridoma Bank); rat anti-mouse AIRE (1:300; Millipore); rat anti-mouse FOXP3 (1:100; eBioscience); biotin-UEA (Biotinylated Ulex Europaeus Agglutinin I) (1:800; Vector Laboratories). Rabbit anti-CD3 primary antibody (1:100; ThermoFisher Scientific) was used on gut sections.\n\nTo quantify abnormalities of colon pathology, a histological score was used. The degree of colic alterations was blindly graded using combined scores including: the grade of inflammation (grade 0, no evidence of inflammation; grade 1, low; grade 2, moderate; grade 3, high; grade 4, intense and diffuse level of inflammation), the structural changes of intestinal layers (grade 0, absence; grade 1, focal; grade 2, partial; grade 3, diffuse level of structural changes), and the gland secretion alterations (grade 0, normal; grade 1, slight gland secretion alterations; grade 2, moderate; grade 3, diffuse gland secretion alterations). The cumulative total scores ranged from 0 to 10.\n\nHuman thymic tissue sample was formalin-fixed and paraffin-embedded. Sections were used for routine H&E staining and treated as described above. Nonspecific background was reduced with Background Sniper (Biocare Medical, Concord, CA, USA) before heat-based antigen-retrieval treatment and incubated with primary antibodies. The following primary antibodies were used: rat anti-human FOXP3 (1:100; eBioscience), mouse anti-human AIRE (1:3000; kindly provided by Prof P. Peterson, University of Tartu, Tartu, Estonia), biotin-UEA (Biotinylated Ulex Europaeus Agglutinin I) (1:800; Vector Laboratories) and Claudin-4 (used according to local standards of Pathological Anatomy Unit of Spedali Civili, Brescia, Italy). Sections were processed as described above for the murine experiments. Morphometric analysis was performed using Olympus Slide Scanner VS120-L100 (Olympus, Tokyo, Japan) and Image-pro software (Olympus) was used to analyze them. Digital images were acquired with the same instruments and software as described above.\n\nMurine Cell Isolation\n\nMurine TEC isolation was performed on age-matched WT and Aβ0/0 mice. Briefly, mice were sacrificed by decapitation to avoid excessive bleeding during surgery. Murine thymus was cleaned from fat and stromal tissues, and then digested at 37°C with an enzymatic solution containing Liberase TL and DNAse I (Roche). Digested tissues were collected in DMEM (Lonza) supplemented with 10% fetal bovine serum (FBS), 1% glutamine and 1% penicillin and streptomycin. Single thymic cell suspensions were then incubated with anti-CD45 micro-beads (Miltenyi Biotec) and processed with the AutoMACS Pro Separator (Miltenyi Biotec). The CD45 negative fraction was retrieved and then tested by multicolor FACS analyses for the expression of TEC markers.\n\nThymocytes, splenocytes and lymphocytes were freshly isolated by mechanically disrupting the thymus, the spleen and lymph nodes of age-matched WT and Aβ0/0 mice. In addition, splenocytes were lysed with Red Cell Lysis Buffer (RCLB) (150mM M NH4Cl, 10 mM KHCO3, and 0.1 mM EDTA). PB samples underwent red blood cell (RBC) lysis twice with RCLB, before further processing. Recovered cells were re-suspended in D-PBS (EuroClone, Pero, Italy) with 2% FBS and subsequently stained for flow cytometric analysis. CD4+ T cells were isolated by pooled spleens and mesenteric lymph nodes (MLNs) from 2–3 mice/pool of age-matched WT and Aβ0/0 mice using CD4-specific magnetic beads via negative selection according to the manufacturer’s instructions (CD4+ isolation kit Miltenyi Biotec).\n\nFlow Cytometric Analysis of Murine Cells\n\nThe list of monoclonal antibodies used for the staining of murine TEC, thymocytes, splenocytes and lymphocytes derived from lymph nodes are reported in the Materials and Methods section in this article’s Supplementary Materials . Cells were acquired on a FACS CANTO (BD Pharmingen) and analyzed with FlowJo software.\n\nCell Sorting of Murine TEC\n\nTECs were isolated and enriched with the AutoMACS Pro Separator after digestion of thymi from pool of 5–10 age-matched WT and Aβ0/0 mice of 4–6 weeks of age, as previously described. To sort mTEC and cTEC, isolated TECs were stained with anti-CD45 (30-F11), anti-CD326 (EpCam; G8.8), anti-MHCII (M5 114.15.2) (all Biolegend), anti-Ulex-1 (FL 1061, Vector) and anti-Ly51 (6C3, Miltenyi) monoclonal antibodies and sorted with the MoFlo Legacy cell sorter (Becton Dickinson), with 100 μl noozle (FRACTAL facility of San Raffaele Hospital, Milan, Italy). Non-viable cells were excluded from analyses using 7-AAD (BD Pharmingen). In order to preserve RNA quality for further analyses, ProtectRNATM RNase Inhibitor (Sigma-Aldrich) was added to CD45-negative fractions according to manufacturer’s instruction, before sorting procedure. Moreover, TEC subsets were sorted directly in RNAlater (Sigma-Aldrich), kept at +4°C overnight and then at −20°C until use.\n\nRT-PCR\n\nRNA extraction from sorted TEC from WT and Aβ0/0 mice was performed with RNeasy microkit (QIAGEN, Hilden, Germany) according to manufacturer’s instructions. RNA was then stored at −80°C until use. Reverse transcription of murine-sorted TEC mRNA, synthesis and amplification of cDNA were performed with the Ovation PicoSL WTA System V2 (Nugen), according to the manufacturer’s instructions. Purification of amplified cDNA was achieved using the QIAquick PCR Purification Kit (QIAGEN). Quantitative Real-time (RT) PCR was performed using Fast SYBR green master Mix (Thermo Fisher Scientific) and the ViiA7 Real-Time PCR System (Thermo Fisher Scientific). Each sample was analyzed in duplicate. The relative level of expression was determined by normalization to β-actin (Actb) ribosomal RNA. The primers used are listed in Supplementary Table 1 .\n\nBulk RNA-Seq\n\nThe cDNA libraries of sorted cTEC and mTEC from WT and Aβ0/0 mice were constructed using the Takara SMART-Seq v4 Ultra low input RNA Kit. PCR library products were quantified using the Agilent DNA 1000 assay (Agilent#5067-1504) on an Agilent Technologies 2100 bioanalyzer. Pooled libraries were loaded on a Paired End Flow Cell using the cBot System (Illumina) and the HiSeq 3000 platform. At the end of the run, around 30 M of 50 bp paired-end reads per sample were generated. Transcript abundance was estimated with Kallisto (29) and differentially expressed (DE) genes were identified using DeSeq2 (30) R package and a FDR corrected p-value <0.05. Gene set enrichment analysis (GSEA) was applied in order to identify gene sets and pathways that were significantly perturbed across conditions. Collections of gene sets were downloaded from MiSigDB (http://www.broadinstitute.org/gsea/msigdb/). We used the Benjamini–Hochberg method to adjust gene set p-values and set 0.1 as the significant threshold. Splicing entropy was calculated on TRA transcripts as described in (31). RNA-Seq data are available under accession number GSE166463.\n\nSample Preparation and Proteomic Analyses\n\nMurine TEC for proteomic analyses were obtained from three pools of WT or Aβ0/0 mice, three mice per pool (5–6 weeks-old). TEC were isolated, enriched and processed through CD45+ cell-depletion as described above. CD45- cell-samples were pelleted and stored at −80°C until use. Detailed descriptions of proteomic analysis, data processing, and interaction network reconstructions are described in the Materials and Methods section in this article’s Supplementary Materials .\n\nAutoantigen Array\n\nThis analysis was performed at the Genomics & Microarray Core Facility at UT Southwestern Medical Center (USA) on human and murine serum or plasma samples. The Autoantigen array contained 95 autoantigens and eight internal control antigens. Profiling of both IgG and IgM autoantibodies was performed. The autoantibodies binding to the antigens on the array were detected with Cy3 labeled anti-IgG and Cy5 labeled anti-IgM and the arrays were scanned with GenePix® 4400A Microarray Scanner. The images were analyzed using GenePix 7.0 software to generate GPR files. The averaged net fluorescent intensity (NFI) of each autoantigen was normalized to internal controls (IgG or IgM).\n\nInduction of Colitis by Adoptive T-Cell Transfer\n\nCD4+ T cells were isolated from pooled spleens and MLNs of 9–10 wk-old WT or Aβ0/0 mice as described above. Enriched CD4+ T-cell samples were subsequently sorted into naive CD4+CD25−CD45RBhi and regulatory CD4+CD25hiCD45RB− cell populations (>98% purity) using a FACS Aria Fusion (Becton Dickinson) cell sorter (FRACTAL facility of San Raffaele Hospital, Milan, Italy). For colitis induction, 4 × 105 WT CD4+CD25−CD45RBhi naive T cells were transferred by intraperitoneal injection (i.p.) into 8–9 week-old Rag1−/− mice alone or with 1.5 × 105 CD4+CD25hi Treg cells from WT or Aβ0/0 mice. Recipient mice were weighted twice a week and sacrificed at week 4 or 8 after the transfer, when colitis was diagnosed by severe weight loss and/or wasting diarrhea. Gut tissues were isolated and analyzed as described and the colon length was measured at time of sacrifice.\n\nFlow Cytometric Analysis on Human PBMC\n\nPBMC were isolated from PB of HD and patients by density gradient centrifugation using LymphoprepTM (density: 1.077 g/ml; STEMCELL Technologies, Vancouver, Canada). PBMC were maintained in RPMI medium (CORNING) with 2% FBS, 2% L-glutamine, 1% Penicillin/Streptomycin at 4 °C until use or live frozen in FBS + dimethyl sulfoxide (DMSO) 10%. Multi-color immunophenotype of T-lymphocyte subsets on human PBMC was performed by flow cytometry. Details about the monoclonal antibodies used for each staining are reported in the Materials and Methods section in this article’s Supplementary Materials .\n\nELISA Assay\n\nLevels of B-cell activating factor (BAFF) were measured in duplicate in serum or plasma samples of MHCII-D patients and age-matched HD using a Quantikine Human BAFF/BLyS/TNFSF13B Immunoassay kit (R&D Systems, Minneapolis, USA). The assay was performed according to manufacturer’s instructions and the optical density (OD) was determined using a microplate reader.\n\nStatistical Analyses\n\nAll results are expressed as median and interquartile range if not stated otherwise. In the present study a descriptive statistical analysis has been performed. No formal inference was performed due to the small sample size. Statistical significance was assessed using a two-tailed Mann–Whitney test to compare continuous outcomes between groups. T test was used for splicing entropy result analysis. Levels of significance were defined as p ≤0.05 (*), p <0.01 (**), p <0.001 (***), and p <0.0001 (****). Statistical testing was performed using Prism GraphPad (Version 5.0f, La Jolla, CA). Graphs were created using the same software.\n\nResults\n\nThymic Structure Perturbation in Absence of MHC Class II Expression in a MHCII-D Patient and in Aβ0/0 Mice\n\nData about human thymic histology in patients with MHCII deficiency are limited because of the difficulties in accessing these tissues for technical and ethical reasons. In this study, we had the unique opportunity to perform histological analysis of a thymic biopsy performed in a 23-month-old MHCII-D female patient before HSCT (see Table 1 for immunological data). The patient carried a homozygous mutation in the CIITA gene [c.3317 + 2dup], resulting in an intronic splice variant.\n\nThe thymic architecture was perturbed, with reduced representation of thymic medulla ( Figure 1A ), as compared to a control thymus analyzed in parallel. This finding was also supported by staining for Ulex Europaeus Agglutinin I (UEA1) and FOXP3 ( Figure 1B ). Moreover, the MHCII-D thymus presented a reduced frequency of AIRE+ and CLAUDIN 4 (Cldn4)-expressing TEC, suggesting possible defects of central tolerance ( Figures 1C, D ).\n\nFigure 1 Thymic structure perturbation in a MHCII-D patient’s thymus. (A) Histological analysis of a MHCII-D patient’s thymus. Immunohistochemistry analysis of thymic tissue isolated from a human healthy donor (HD) and a MHCII-D patient. Hematoxylin–eosin (H&E) staining shows a reduced representation of thymic medulla. Original magnification 4×, corresponding to 500 μm. (B) UEA1 and FOXP3 staining in MHCII-D thymus. Immunohistochemistry analysis of Ulex Europaeus Agglutinin I (UEA1) and FOXP3 expression in a thymic tissue isolated from a human HD and a MHCII-D patient. Original magnifications: 20× for UEA1 and 10x for FOXP3 staining images, corresponding respectively to 100 and 200 μm. (C) AIRE and CLDN4 expression in MHCII-D thymus. Immunohistochemistry analysis of CLDN4 (Claudin 4) and AIRE expression in a thymic tissue isolated from a human HD and a MHCII-D patient. Original magnifications: 20× for CLDN4 and 40× for AIRE staining images, corresponding respectively to 100 and 50 μm. (D) AIRE expression is reduced in MHCII-D thymus. Comparison of the concentration of AIRE+ cells per square millimeter (mm2) in a thymic tissue isolated from a human HD and a MHCII-D patient. Mann–Whitney test, p-value < 0.001. Bars represent median with interquartile range. ***p value < 0.001.\n\nTo further corroborate these observations, we analyzed thymic tissue isolated from the MHCII knock out mouse model, Aβ0/0 (17, 18). Histological analysis showed similar abnormalities of thymic architecture, with reduced representation of TECs, especially in the medulla, resulting in a significantly increased cortico-medullary (C/M) ratio in Aβ0/0 mice, as compared to WT mice (p-value 0.0087) ( Figures 2A, B ). However, CK5, a medulla specific marker, and CK8 staining indicated a correct compartmentalization of cortical and medullary areas in the thymus of Aβ0/0 mice ( Supplementary Figure 1A ). Overall reduced total Epcam+ TEC and mTEC frequency and absolute count in Aβ0/0 thymi, as compared to WT, were confirmed by flow cytometric analysis ( Figure 2C and Supplementary Figure 1B ). Finally, we detected a decreased frequency of AIRE+ TEC and FOXP3+ cells in the medullary area of Aβ0/0 mice thymus, as compared to WT mice ( Figures 2D, E and Supplementary Figure 1A ).\n\nFigure 2 Thymic structure perturbation in Aβ0/0 mice thymus. (A) Reduced thymic medulla representation in Aβ0/0 mice, confirmed by H&E staining as compared to WT mice. Scale bars correspond to 500 μm. (B) Increased cortico-medullary (C/M) ratio in Aβ0/0 mice. Mann–Whitney test, **p-value <0.01. Median with interquartile range is showed in the graph for each experimental group. (C) Reduced frequency (left panel) and absolute count (right panel) of TEC and mTEC in Aβ0/0 mice after enzymatic digestion of thymic tissue and depletion of CD45+ cells. Mann–Whitney test, *p value < 0.05; **p value <0.01. (D) Immunohistochemical analysis of AIRE expression in WT and Aβ0/0 mice thymi. Original magnification: 20× for left panel and 40× for right panel for each condition, corresponding respectively to 100 and 50 μm. (E) Frequency of AIRE-expressing cells (AIRE+) is reduced in Aβ0/0 thymus. Comparison of the concentration of AIRE+ cells per mm2 of total thymic tissue isolated from WT or Aβ0/0 mice. Mann–Whitney test, *p-value < 0.05. Median with interquartile range is showed in the graph for each experimental group.\n\nImpaired Generation and Maturation of CD4+ SP Thymocytes in Aβ0/0 Mice and MHCII-D Patients\n\nIn accordance with previous reports (17, 18, 24), we observed a reduction in the frequency and in the absolute count of CD69hiTCRβhi thymocytes ( Figures 3A, B and Supplementary Figure 2A ), and severe defects of CD4+ SP thymocyte generation and maturation ( Figures 3C, D and Supplementary Figure 2B ) in Aβ0/0 mice, in line with the known fundamental role of MHCII molecules for the progression from the DP stage to the SP CD4+ T cell stage (18). Moreover, we confirmed that that majority of these residual SP CD4+ thymocytes in Aβ0/0 mice corresponds to CD1-restricted NKT cells, as previously described (20, 21) ( Supplementary Figure 2C ). This resulted in peripheral CD4+ T cell lymphopenia, with significant reduction in the frequency and absolute count of CD4+ naïve T cells and increased frequency of activated CD4+ T cells in secondary lymphoid organs (spleen and lymph nodes), as compared to WT CD4+ SP cells (SP4) cells ( Supplementary Figures 2D, E ).\n\nFigure 3 Defective thymopoiesis in MHCII deficiency. (A) FACS analysis of thymocytes isolated from WT and Aβ0/0 mice, in terms of CD69 and TCRβ expression, shows an impaired positive selection of Aβ0/0 thymocytes. Analysis performed on total thymocyte gate. (B) Graph shows the summary of all mice analyzed, showing a significant reduction in the frequency of CD69hiTCRβhi post-positive selection thymocytes in Aβ0/0 mice, as compared to WT. **p value < 0.01; ***p value < 0.001. (C) FACS analysis of thymocytes isolated from WT and Aβ0/0 mice shows a normal development of CD4−CD8− double negative (DN) subsets. However, Aβ0/0 mice CD4+ SP cells (SP4) mostly present an immature phenotype (CD24+), since only few of them are CD24−, as compared to WT SP4 cells. (D) Graph shows the summary of all mice analyzed in terms of frequency of CD24+ and CD24− SP4 and SP8 cells. *p value < 0.05; ***p value < 0.001; ****p value < 0.0001. (E, F) TCR Vα7.2 expression on CD3+ T cells is reduced in MHCII-D patients. (E) Representative FACS plots on Vα7.2 expression on CD3+ T cells on a healthy control (HD) and a MHCII-D patient (MHCII_13). (F) Graph shows the summary of all MHCII-D patients analyzed (n = 4) and the healthy controls (HD) tested in parallel. Median and interquartile range are represented for each group. (G) Representative FACS plots of CD4+ naïve T cells and recent thymic emigrants (RTE) of a healthy control (HD) and three MHCII-D patients, two before HSCT (MHCII_11 and _12) and one after HSCT (MHCII_08). CD27+CD45RA+ naïve T cells are gated on CD4+CD3+CD45+ T-cell gate, while CD31+ RTE are gated on CD27+CD45RA+ naïve T cell gate.\n\nSince we could not get access to thymocytes from MHCII-D patients, we investigated TRAV1 (Vα7.2) expression on patients’ PB CD3+ lymphocytes as a surrogate marker of thymocyte maturation and survival (32). Interestingly, we found that all four patients analyzed (three before and one after HSCT) showed a trend towards reduced expression of Vα7.2 on their CD3+ T cells as compared to normal controls tested in parallel (median: MHCII-D 2.1%; HD 6.8%) ( Figures 3E, F ).\n\nReduced Frequency of Naïve CD4+ T-Cells and RTE in Untreated MHCII-D Patients\n\nIn order to evaluate thymic output in MHCII deficiency, we analyzed the proportion of naïve T cells and recent thymic emigrants (RTE) among PBMC from three patients: two untransplanted [of whom one infant (MHCII_11) and one adult (MHCII_12)], and one transplanted patient (MHCII_08). The percentage of naïve CD45RA+CD27+CD4+ T cells was reduced in the two untreated patients, as compared to the normal donor tested in parallel. Conversely, naïve CD4+ T cells in the transplanted patient tended to normal levels ( Figure 3G ). No significant differences emerged in the proportion of naïve CD8+ T cells (data not shown). We identified RTE as CD31+ cells within naïve CD27+CD45RA+CD4+ T cells. In line with data on naïve CD4+ cells, the frequency of RTE in the two untransplanted patients was also reduced ( Figure 3G ). This finding was particularly striking for the infant patient. RTE in MHCII_08, who underwent transplant, were comparable to the adult control tested in parallel ( Figure 3G ).\n\nTEC Transcriptome and Proteome Perturbation in the Absence of MHC Class II\n\nBased on our observations of TEC abnormalities in histologic analysis of thymic samples, we evaluated gene expression profile of Aβ0/0 mouse TEC subsets by performing bulk RNA-Seq on sorted WT and Aβ0/0 cTEC and mTEC. In order to obtain a sufficient amount of sorted TEC, we pooled 5–10 WT or Aβ0/0 mice of 4–6 weeks of age for each biological replicate (n = 3, Supplementary Table 2 ). The gating strategy used to sort cTEC (Epcam+CD45−Ly51+UEA1− cells) and mTEC (Epcam+CD45−Ly51−UEA1+ cells) is shown in Supplementary Figure 3A . Principal component analysis (PCA) showed that samples were properly grouped according to genetic background and tissue of origin ( Supplementary Figure 3B ).\n\nTranscriptome analysis revealed an altered gene expression profile in sorted TEC subsets from Aβ0/0 mice, as compared to age-matched WT mice. These differences were especially prominent in mTEC ( Figure 4A and Supplementary Table 3 ), on which we subsequently focused our analyses. In particular, we identified almost one thousand (n = 929) transcripts that were differentially expressed (DE) in mTEC from WT versus Aβ0/0 mice. The majority of these transcripts (n = 679, in red in Supplementary Figure 4A ) were upregulated in mTEC from WT mice ( Supplementary Table 3 ). Among DE genes, transcripts that were enriched in Aβ0/0 mTEC (n = 250) were mainly relative to RNA splicing, histone modifications and transcription factors (most of which with repressive function) ( Figure 4B ).\n\nFigure 4 Transcriptome and proteome perturbation in absence of MHCII molecules. (A) Heat map of expression values for genes that were differentially expressed between Aβ0/0 and WT mice cTEC or mTEC at a p value cut-off (FDR-corrected) of 0.05. Rows (genes) are scaled, i.e., the value (z score) for a gene in a given sample represents its deviation from the mean expression value of the gene across all samples in terms of standard deviations. Up regulation is shown in red, down regulation in blue. Genes and samples are ordered by hierarchical clustering using Pearson’s correlation as the distance measure and complete linkage as the clustering method. (B) Network analysis of differentially expressed transcripts in mTEC. The figure shows the main results of network/topology analysis based on the combination of the list of DE transcripts in mTEC with Mus musculus Protein–Protein Interaction (PPI) network using STRING bioinformatics tool (full figure is reported in Supplementary Figure 4A ). In red are represented transcripts up-regulated in WT mTEC, in light blue those up-regulated in Aβ0/0 mTEC. (C) Cluster-Network analysis of differentially expressed proteins in CD45-depleted TEC fractions. The figure shows the main results of network/topology analysis based on the combination of the list of DE proteins in CD45-depleted TEC fractions with Mus musculus Protein–Protein Interaction (PPI) network using STRING bioinformatics tool (full figure is reported in Supplementary Figure 4B ). In red are represented proteins up-regulated in WT mice, in light blue those up-regulated in Aβ0/0 mice. (D) Transcript and protein expression per functional cluster in WT and Aβ0/0 cell subsets. For each cluster, the proportion of enriched transcripts or proteins in WT (red) or Aβ0/0 (blue) are represented as percentage in the respective pie charts. Data about transcripts were obtained from sorted mTEC, data about proteins were obtained from CD45-depleted TEC samples.\n\nSimilarly, even if to a lesser extent, cTEC transcriptome resulted also altered ( Figure 4A and Supplementary Table 3 ) in Aβ0/0mice. Differentially expressed transcripts upregulated in Aβ0/0 cTEC were mainly relative to RNA splicing and translation, carbohydrate metabolism and cytoskeleton. Conversely, in WT cTEC enriched DE transcripts resulted relative to lipid metabolism, peptidases, apoptosis, transmembrane transport, transcriptional regulation, blood vessels/extracellular matrix, cytokine signaling pathway, inflammatory and immune response ( Supplementary Figure 5 ).\n\nTo further define the cellular features of TEC in Aβ0/0 mice, we performed proteomic analysis of bulk CD45-depleted TEC fractions from pools of 4–6-week-old WT and Aβ0/0 mice (n = 3, three mice/pool). This analysis could not be performed on sorted TEC subsets due to technical limitations. In these cell subsets, we found 373 DE proteins, 111 of which with high confidence ( Supplementary Tables 4 and 5 ). Most of these proteins were upregulated in WT mice (in red in Supplementary Figure 4B ). Among DE proteins, the only ones that were enriched in Aβ0/0 TEC-enriched subsets were relative to chromatin assembly, in particular histones, as indicated by combined cluster-network analysis ( Figure 4C ). We cannot exclude the presence of some fibroblasts and endothelial cells in the analyzed samples.\n\nNext, we performed an integrated network analysis on DE transcripts and proteins in WT and Aβ0/0 TEC in order to identify common specific pathways dysregulated in TEC in the absence of MHCII. The only common variation observed in both cTEC and mTEC transcripts and in CD45-depleted TEC fractions was an increased representation of transmembrane transporter activity in WT mice thymi. However, if restricting the analysis to mTEC only, a concordant pattern of variations in both transcripts and proteins within the same cluster between WT and Aβ0/0 mice was observed for four clusters ( Figure 4D ). In particular, in WT mice, increased expression was observed for genes and proteins involved in cell metabolism, energy production and cell cycle.\n\nImpaired Promiscuous Gene Expression in the Absence of MHCII Molecules\n\nNext, we interrogated RNA-Seq data for genes known to be involved in the establishment and maintenance of central tolerance. GSEA showed a significant enrichment for both Aire-dependent and Aire-independent transcripts known to have a tissue-restricted pattern of expression, also known as Tissue Restricted Antigen (TRA) genes, in WT mTEC ( Figure 5A ). Reduced expression of TRA genes in Aβ0/0 mTEC emerged also at DE analysis and was confirmed by qRT-PCR analysis for a selected number of them ( Figures 5B, C ). Consistent with these observations, Aire gene expression was significantly reduced in Aβ0/0 mTEC, as compared to WT (Log2 fold change mTEC WT/Aβ0/0: 2.12, adjusted p-value: 0.0017) and this result was confirmed by qRT-PCR ( Figures 5B, C ). These results confirm and extend previous observations (24). In addition, we confirmed reduced Aire expression also at the protein level, as shown by intracellular FACS analysis ( Figure 5D ). Analysis of Fezf2 expression did not reveal any relevant differences in Aβ0/0 and WT mTEC ( Figures 5C, D ). In addition, DE analysis suggested a disruption of the mechanisms controlling Aire expression in Aβ0/0 mTEC, as indicated by a significantly reduced expression of the transcripts encoding for the protein deacetylase Sirtuin-1 (Sirt1) and Irf8 in Aβ0/0 mTEC ( Figure 5B ), respectively an essential Aire regulator and an Aire transcriptional activator. Finally, in order to further investigate mTEC functionality (34), we also calculated TRA splicing entropy (31), a measure of the diversity of transcripts isoforms, which resulted decreased in Aβ0/0 mTEC ( Figure 5E ). This disruption of the complex machinery regulating Aire expression could be due to Aβ0/0 mTEC impaired maturation. Collectively, these findings suggest that lack of MHCII expression in mTEC is associated with impaired promiscuous gene expression (PGE) and abnormalities of the mechanisms that govern central tolerance.\n\nFigure 5 TEC transcriptome perturbation in the absence of MHC class II. (A) Enrichment Analysis of Gene Sets involved in promiscuous gene expression and maturation in mTEC. The normalized enrichment score (NES) is reported for each gene set. Positive NES indicate gene sets enriched in WT mTEC, negative NES indicate gene sets enriched in Aβ0/0 mTEC. This analysis was performed based on gene lists published in (33). (B) Volcano plot representing results of differential gene expression (DE) analysis of genes between WT and Aβ0/0 mTEC. In red are represented genes more expressed in WT mTEC, in light blue those more expressed in Aβ0/0 mTEC. In orange are evidenced genes with tissue-restricted expression (TRE). (C) Absolute mRNA level of Aire, Fefz2, and some TRA (Aire- or Fezf2-dependent), quantified by RT-PCR performed on sorted WT or Aβ0/0 mTEC, pooled from 2–3 sorting experiments. Ins2, insulin; Spt1, serine palmitoyltransferase; Nol4, nucleolar protein 4 (testis); Calb1, calbindin (brain, kidney), Fabp9, fatty acid binding protein 9 (testis); Csrnp3, cysteine-serine-rich nuclear protein 3. (D) AIRE protein expression is reduced in mTEC lacking MCHII. Graph shows the mean fluorescence intensity (MFI) of AIRE and FEZF2 proteins by flow cytometry in total mTECs after intracellular staining in WT (n = 7) or Aβ0/0 (n = 8) mTEC, respectively. **p-value < 0.01. (E) Splicing entropy, a measure of the diversity of observed transcripts isoforms in a given sample, resulted decreased in Aβ0/0 mTEC. The analysis was restricted to TRA only. The formula used for the calculation of mRNA splicing entropy was derived from (31). Results are expressed as mean and standard deviation. *p value < 0.05.\n\nImpaired mTEC Maturation in Aβ0/0 Mice\n\nRNA-Seq results showed a significantly decreased expression of genes involved in mTEC maturation in Aβ0/0 sorted mTEC. Accordingly, GSEA showed a significant enrichment in genes known to be expressed in mature mTEC in WT mice, while genes known to be expressed in immature mTEC where significantly enriched in Aβ0/0 mTEC (33) ( Figure 5A ). Moreover, DE gene analysis showed a significantly increased expression of co-stimulatory molecules (mainly CD86 and ICOS ligand, which are involved in TEC-thymocyte cross-talk), in WT mTEC, as compared to their Aβ0/0 counterpart ( Figure 5B ). A similar pattern was observed for transcripts encoding for molecules involved in NF-κB signaling, and in particular for CD40, which was more abundantly expressed in WT mTEC ( Figure 5B ). These results were confirmed when analyzing numbers of CD40L+ and RANKL+ thymocytes in Aβ0/0 mice. Indeed, we detected by flow cytometry a severe reduction of both CD40L+ and RANKL+ thymocyte absolute counts in Aβ0/0 mice ( Supplementary Figure 6 ), suggesting a low CD40L and RANKL-mediated stimulation of Aβ0/0 mTEC. This reduction was particularly evident in mice aged 3 weeks or older ( Supplementary Figure 6 ).\n\nAbnormalities of Peripheral Tolerance in Aβ0/0 Mice\n\nBased on the alterations detected in the thymus of MHCII deficient patients and mice, we hypothesized that impairment in central tolerance mechanisms could have an impact also on peripheral tolerance. In line with published results for another MHCII mouse model, the Aα−/− mice (25), Treg cells were nearly absent in the thymus of Aβ0/0 mice, but they appeared relatively enriched in spleen and lymph nodes where they were present at higher frequency than in WT mice ( Figure 6A , left panel). Nonetheless, Treg absolute count was reduced in all lymphoid organs in Aβ0/0 mice ( Figure 6A , right panel).\n\nFigure 6 Peripheral tolerance impairment in Aβ0/0 mice. (A) Frequency and absolute count of Treg cells in WT and Aβ0/0 mice. (Left panel) Frequency of Treg cells is expressed as the percentage (%) of FoxP3+CD25hi cells gated on CD4+ T-cell gate. (Right panel) Absolute count of Treg cells. THY, thymocytes; SPL, spleen; LN, lymph nodes. *p-value < 0.05; ***p-value < 0.001. (B) Colon length in the different treatment groups of induced colitis experiments. The graph shows the colon length of n = 3–7 mice/group from three experiments. Median score is reported for each treatment group. Error bars represent interquartile range. *p-value < 0.05; ns, not significant. (C) Histological analysis of the colon of treated mice. Representative colonic sections from Rag1 ko mice who received administration of WT T cells alone or in combination with WT or Aβ0/0 Treg cells, stained with H&E (left panels) and CD3 immunostaining (right panels). Original magnifications: 10× for H&E, 20× for CD3 staining. (D) Colitis score in the different treatment groups of induced colitis experiments. The graph shows the inflammation score in the gut of n = 3– mice/group from three experiments. Median score is reported for each treatment group. Error bars represent interquartile range. *p-value < 0.05; **p-value < 0.01; ns, not significant.\n\nWe then tested in vivo the function of Aβ0/0 Treg cells. To this purpose, we made use of a model of colitis induced by adoptive transfer of WT T cells, alone or in combination with WT or Aβ0/0 Treg cells, into Rag1 ko mice ( Supplementary Table 6 ), and analyzed the capacity of Treg cells to attenuate colitis. Recipient mice were monitored weekly and sacrificed four or eight weeks after the transfer, when signs of colitis (wasting diarrhea and weight loss) became evident in mice that had received WT T naive cells only or in combination with Aβ0/0 Treg cells ( Supplementary Figure 7A ). At sacrifice, the gut tissue was analyzed macroscopically and colon length, an indirect sign of gut inflammation (35), was measured. As shown in Figure 6B , colon length in mice receiving co-injection of WT Treg cells together with WT T naïve cells, was similar to that of untreated mice. Conversely, colon length was reduced in mice receiving WT naïve T cells alone and in those receiving co-injection of Aβ0/0 Treg cells together with WT naïve T cells. Moreover, in mice that received either WT naïve T cells only or in combination with Aβ0/0 Treg cells, the study of intestinal pathology revealed different degrees of spontaneous colitis and wasting diarrhea. Substantial thickening of colonic mucosa, indicative of inflammation, was observed. Histologically, colonic inflammation was characterized by crypt elongation and large inflammatory cell infiltrate, mainly consisting of T lymphocytes, with occasional crypt abscesses ( Figure 6C ). A colitis score was calculated on histological sections of gut tissue based on the sum of the evaluation of architectural alterations, degree of inflammation and muciparous gland activity (see Materials and Methods for details). When compared to untreated animals, the colitis score was significantly increased in mice receiving WT naïve T cells alone or in combination with Aβ0/0 Treg cells, while it was not statistically different in mice receiving both WT naïve T cells and WT Treg cells ( Figure 6D ). Furthermore, among the four treatment groups, only mice that had received co-transplantation of WT Treg cells showed an increased proportion of Treg cells in the spleen and MLN at sacrifice ( Supplementary Figures 7B, C ). Altogether, these results demonstrate that adoptive transfer of Aβ0/0 Treg cells failed to block colitis induction in Rag1 ko mice, suggesting an impaired function of these cells.\n\nPeripheral Tolerance Impairment in Patients With MHCII Deficiency\n\nTo confirm the results obtained in the mouse model of MHCII deficiency, we set out to evaluate peripheral tolerance in MHCII-D patients. To this purpose, we collected PB samples from a cohort of patients with MHCII deficiency, whose main clinical features are summarized in Table 2 . RFXANK gene mutations were identified in eight of them. Median age at sampling was 4.7 years (range: 0.4–24.1 years). All samples were collected before HSCT, except in one patient for whom only post-transplant sample was available. They suffered from severe and recurrent infections and the majority of them also presented with chronic diarrhea. Autoimmune manifestations were described in three patients. Available data about patients’ immune phenotype and serum immunoglobulin levels are reported in Table 3 . Most patients were treated with immunoglobulin replacement therapy and anti-infective prophylaxis, as standard supportive care. Seven patients were treated with HSCT, at a median age of 4.5 years (range: 1.1–16.2 years). Characteristics and outcome of HSCT are detailed in Table 4 .\n\nWe first investigated the frequency of circulating Treg cells in three MHCII-D patients. Treg cells were defined as CD4+CD25hiCD127loFOXP3+ cells. Moreover, in order to differentiate thymic from peripherally induced Treg cells we also stained cells for the expression of HELIOS. The frequency of Treg cells was slightly reduced in one of the untransplanted patients (MHCII_11), as compared to published reference values (36). However, the other two patients showed a frequency of Treg cells comparable to the normal donor, and within normal range also as compared to published references ( Figure 7A and Supplementary Table 7 ). Interestingly in all patients, most CD4+CD25hiCD127loFOXP3+ cells were also positive for HELIOS, suggesting their likely thymic origin ( Supplementary Table 7 ).\n\nFigure 7 Peripheral tolerance impairment in patients with MHCII deficiency. (A) Treg cell frequency in MHCII-D patients. Representative FACS plots of Treg cells in three patients with MHCII-D and a HD. Treg cells are defined as CD4+CD25hiCD127loFOXP3+ cells. In upper panels CD25hiCD127lo cells are represented, gated on CD4+ T-cell gate. In lower panels, FOXP3+ cells are represented, gated on CD25hiCD127lo cells. FOXP3 gate was set based on fluorescence-minus-one (FMO) control on normal donor cells. (B) Autoantibodies are present in the serum of MHCII-D patients. Patients’ serum was tested for the presence of a large panel of 95 autoantibodies. Heatmap colors correspond to z-score, i.e. the number of standard deviations from the mean signal intensity of the autoantibody across all samples. Color legend over the panel show: pink box, MHCII-D patients; light blue box, age matched normal controls (HD); green, positive control (serum of a patient with systemic lupus erythematous, kindly provided by Stefano Volpi, Genova, Italy). T symbols identify the sample of a MHCII-D patient after HSCT. Statistical analysis included only not transplanted MHCII-D patients. (C) BAFF level in MHCII-D patients’ sera. Serum BAFF concentration was determined by ELISA in 11 age-matched healthy controls (HD) and in eight MHCII-D patients (one of whom after HSCT). Each symbol represents an individual, and the median is represented with a horizontal bar. Error bar shows the interquartile range.\n\nWe then investigated possible tolerance breakdown as a result of impaired T-B cell cross-talk in the absence of MHCII molecules. In order to evaluate the presence of autoantibodies in the serum of MHCII-D patients, we performed a protein microarray (37) to screen for a large panel of IgG and IgM autoantibodies. This assay revealed a significantly increased titer of many different autoantibodies, especially of IgG isotype, in the serum of MHCII-D patients ( Figure 7B ), as compared to healthy controls. Furthermore, BAFF levels, which are known to play a role in B-cell homeostasis and peripheral tolerance (38, 39), were increased in the sera of most of the patients analyzed, as compared to healthy controls ( Figure 7C ). Both findings of multiple serum autoantibodies and increased BAFF levels, even if not linked to overt autoimmune manifestations in most patients, are suggestive for the presence of a defective peripheral B-cell tolerance checkpoint in MHCII-D.\n\nDiscussion\n\nOur findings in the MHCII deficient mouse model and in human samples from MHCII-D patients suggest that lack of MHCII molecules leads to altered thymic structure and function, resulting in a tolerance impairment broader than previously recognized, involving both central and peripheral mechanisms. In particular, thanks to the unique opportunity to analyze a human thymic biopsy, we observed perturbation of thymic structure in a MHCII-D patient, with reduction of thymic medulla and decreased frequency of AIRE+ TEC. These findings are consistent with data obtained in murine models showing thymic structure perturbation with reduced total TEC cellularity and mature mTEC representation. The decreased AIRE+ TEC frequency might be caused by medullary area reduction. However, a significantly reduced expression of Aire and Aire-dependent and -independent TRA mRNA by qRT-PCR was previously reported in another MHCII ko mouse model (Aα−/−) (24), suggesting also a functional impairment. Whether this apparent functional defect can be explained merely by the reduced size of the thymic medulla, due to impaired thymic cross-talk with developing thymocytes, or by intrinsic TEC defects was not clear. To address this point, we performed an in-depth cellular and molecular characterization of TEC in Aβ0/0 mice. Transcriptomic and proteomic studies revealed several differences in the total TEC population and particularly in the mTEC subset, indicative of an overall reduced functionality of these cells in Aβ0/0 mice. Interestingly, an integrated network analysis combining RNA-Seq and proteomic data, revealed potential common processes dysregulated in MHCII ko TEC, mainly involving cell metabolism, energy production and cell cycle, that were downregulated in Aβ0/0 mice. In line with this, previous studies showed reduced mTEC proliferation capacity in MHCII deficient mice (24). Analysis of PGE revealed profound abnormalities in Aβ0/0 mTEC. First, we confirmed known reduced expression of Aire at both mRNA and protein level, while no differences in Fezf2 expression emerged between WT and Aβ0/0 mice mTECs. Moreover, further to previous published observations, we extended the analysis on RNASeq data to thousands of genes known to have a tissue-restricted pattern of expression, which resulted significantly enriched in WT mice mTEC, as compared to Aβ0/0. Following recent evidence highlighting RNA processing as an additional way to expand the diversity of the self-antigen repertoire displayed by mTEC (31, 34), we tested the capacity of WT and Aβ0/0 mTEC to express a great variety of alternatively spliced TRA transcripts. Interestingly, TRA splicing entropy was reduced in Aβ0/0 mTEC, suggesting also a qualitative defect in PGE. Various transcription factors and regulators, which associate with AIRE for its expression and function (40), have been shown to modulate PGE. Here we have shown for the first time that two such factors, Sirt1 and Irf8, that have been previously shown to participate at the control of central tolerance induction (41, 42), are expressed at low levels in Aβ0/0 mTEC. We have further hypothesized that the abnormalities of PGE in Aβ0/0 mice may reflect impaired mTEC maturation. Consistent with this hypothesis, GSEA demonstrated that Aβ0/0 mTEC express reduced levels of many genes known to be expressed in mature TEC, including co-stimulatory molecules and key components of the NF-κB pathway, and in particular CD40, on which mTEC developmental program primarily depends on (43).\n\nThymic cross-talk with developing thymocytes is well-known to a have a fundamental role for the maturation of mTEC, in particular, through RANK-RANKL and CD40-CD40L signaling (24, 43, 44). In line with this, we observed a severe reduction of both CD40L+ and RANKL+ thymocyte absolute count in Aβ0/0 mice. These results support the hypothesis that the underlying cause of reduced mTEC maturation resides in the severe reduction of CD4+ thymocytes, resulting in a low RANKL-mediated stimulation of Aβ0/0 mTEC, in line with previous data reported by Irla et al. (24). This observation would suggest a possible role for exogenous soluble RANKL administration in overcoming mTEC maturation and number defects in this disease, also based on its beneficial effects on thymic cellularity observed in other disease murine models (45, 46).\n\nWe also confirmed impairment of generation and maturation of CD4+ SP thymocytes in Aβ0/0 mice, which resulted in severe reduction of CD4+ T lymphocytes in the periphery, especially in the naïve subset. Defective thymopoiesis in MHCII-D patients has long been considered a reflection of abnormal CD4+ SP thymocytes thymic selection and maturation resulting from the absence of MHCII expression on TEC (1, 4, 6, 7, 47), but no specific studies on patients thymocytes have ever been reported due to technical difficulties in accessing these cells in patients. To overcome this limitation, we investigated TRAV1-2 (Vα7.2) expression on patients’ PB CD3+ lymphocytes, which has been recently described to be severely reduced in patients with immunodeficiencies caused by V(D)J recombination and DNA repair defects (32). The evaluation of TRAV1-2 gene usage allows to indirectly assess the presence of a specific bias in TCRα use, reflecting potential alterations in thymocyte lifespan or alterations in a very specific window of their intrathymic maturation during which thymocytes undergo TCRα rearrangement, the DP stage. Indeed, MHCII molecules are known to have a fundamental role for the progression from this stage to the following SP CD4+ stage (18). Interestingly, we found a trend to reduced expression of Vα7.2 on CD3+ T cells from the four MHCII-D patients analyzed, including one patient after HSCT. As compared to published mean values obtained in pediatric and adult controls (32), expression of Vα7.2 on their CD3+ T cells resulted in the lower end of normal range, suggesting a suboptimal TCRα gene rearrangement in these patients. However, since the expression of Vα7.2 has been shown to be highly heterogeneous (32), both in normal and in general PID population, examining a larger cohort of patients with MHCII-D, both prior and after HSCT, would be needed to confirm this finding. In line with this, previous studies on thymic function in MHCII-D patients reported clonal abnormalities of TCR repertoire and lower TCR gene rearrangement events in patients’ T lymphocytes, as compared to healthy controls (7), suggesting an overall reduced thymic activity in MHCII deficiency and emphasizing the key role of MHCII molecules in the thymic T-cell maturation processes. However, TREC were detected in patients with MHCII deficiency, reflecting normal early T-cell development (4, 7) and published data about naïve CD4+ T-cell count in patients with this condition are inconclusive (7). In our study, we observed a reduced frequency of naïve CD45RA+CD27+CD4+ T cells and RTE in the two untreated patients, especially marked in the infant one.\n\nImmune dysregulation is still a poorly characterized feature of MHCII deficiency. Autoimmunity is reported in 6–20% patients (6). The presentation of self-peptides by MHCII molecules is critical for the maintenance of peripheral T-cell tolerance. mTEC support intrathymic generation of Ag-specific FoxP3+ Treg cells (48–51), together with negative selection of αβ conventional T cells. Based on the alterations detected at thymic level in the absence of MHCII expression, we hypothesized that impairment in central tolerance mechanisms could impinge also on peripheral tolerance establishment and maintenance, in particular by affecting generation of Treg cells. Previous studies in MHCII ko mice provided evidences in favor of this hypothesis (24). However, it has been previously reported that CD4+FoxP3+ Treg cells from MHCII ko mice are capable of mediating immune suppression in vitro (25). In experimentally induced colitis models, regulatory CD25+ DP T cells generated in MHCII ko mice, probably arising from SP CD8+ T cells, have been demonstrated to control the colitogenic potential of CD25-CD4+ T cells (26), but data are missing on the in vivo CD4+ Treg-specific functionality in MHCII ko models. To address this, we tested Aβ0/0 Treg cell capacity to attenuate colitis induced by the injection of WT T naïve cells into Rag1 ko mice. Our experimental data suggest a functional impairment of Aβ0/0 Treg cells in vivo, in contrast to previous reports on their in vitro functionality. This defect in Aβ0/0 mice may be compensated in vivo by tolerogenic CD8+ “Treg-like” cells which have been described to constitutively express CD25, CTLA4 and FoxP3 and have been demonstrated to be able to produce IL-10 and efficiently inhibit CD25- T cell responses to anti-CD3 stimulation (27). These cells might also account, at least in part, for reduced signs of overt spontaneous autoimmunity in Aβ0/0 mice.\n\nLimited data regarding Treg cells have been reported to date in patients with MHCII-D. The frequency of circulating Treg cells within the CD4+ T-cell population was either normal or slightly reduced in the three patients tested. This is in line with a previously published observation (52) in a pediatric MHCII-D patient, in whom a normal frequency of Treg cells was reported, together with reduced absolute number due to severe reduction in total CD4+ T cells in these patients. Of interest, most Treg cells were Helios+, suggesting their likely thymic origin.\n\nImpaired Treg function may also contribute to the impairment of peripheral B-cell tolerance checkpoint through altered cognate T-B cell interactions. This is in line with a previous report on a MHCII-D patient who displayed a low number of Treg cells and failed to counterselect autoreactive mature naïve B cells. This suggests that peripheral B-cell tolerance also depends on MHCII-TCR interactions and that Treg cells may play an important role in preventing the accumulation of new emigrant/transitional autoreactive B cells in the mature naive compartment of these patients (52). We found a significantly increased level of BAFF in the serum of most of MHCII-D patients in our cohort. Our results confirm the preliminary observation of increased BAFF levels in one MHCII-D patient reported by Hervé et al. (52), which was correlated with defective peripheral B-cell tolerance checkpoint in this disease. Elevated BAFF levels lower the thresholds for the survival of autoreactive B cell clones (38) and inhibit the counterselection of autoreactive new emigrant/transitional B cells that fail to be removed from B-cell population. It would be important to understand the causes underlying elevation in BAFF level in MHCII-D patients. Elevated BAFF serum levels are often present in B cell lymphopenic conditions (53), autoimmune diseases (54, 55) and viral infections (56). Increased BAFF levels in MHCII-D are unlikely due to peripheral B-cell lymphopenia, since most patients have normal B cell levels, but are more suggestive of ongoing autoreactivity/autoinflammation. BAFF is known to be produced by myeloid cells. In particular, neutrophils can contribute to excess serum BAFF levels, through which they have been demonstrated to promote CD4+ T-cell and B-cell responses and enhance CD4+ T-cell proliferation and IFNγ secretion in lupus-prone mice (57). Moreover, BAFF has been reported to promote Th1-mediated inflammation through downstream cellular events (58) and to trigger the production of pro-inflammatory cytokines through the activation of the NF-kB pathway (59). These findings indicate a possible link between the chronic infection-driven inflammatory state in these patients and their B-cell tolerance impairment. However, no clear correlation between BAFF levels and autoimmune manifestations emerged from the study of the patients reported here.\n\nIn conclusion, our data highlight the key role of MHCII molecules in both central and peripheral immune tolerance mechanisms, and uncover specific defects in TEC maturation and function, both at transcriptomic and proteomic levels. These results also indicate the need of complementing therapeutic approaches based on HSCT with new therapeutic strategies aimed at correcting the underlying molecular defect also at the TEC level in order to achieve a more effective cure for MHCII-D.\n\nData Availability Statement\n\nRNA-Seq data are available under accession number GSE166463. Data from proteomic analyses are available in MassIVE repository, at the following link: ftp://massive.ucsd.edu/MSV000086866/. Other raw data supporting the conclusions of this article will be made available by the authors upon request, without undue reservation.\n\nEthics Statement\n\nThe studies involving human participants were reviewed and approved by the San Raffaele Ethical Committee. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. The animal study was reviewed and approved by Institutional Animal Care and Use Committee protocol 710-712.\n\nAuthor Contributions\n\nFF performed experiments, analyzed data, and wrote the manuscript. IB performed experiments and analyzed data. RR, GEM, ED, MCC, and GD performed experiments. EF and PLP performed histological analyses on human and murine tissue samples. PU performed RNA-Seq on murine-sorted TEC and data analysis. FB contributed to sample preparation for proteomic studies. DDS performed proteomic and network analyses. DM, CP, TT, VB, ASc, CS, SG, ASo, ARG, SS, BDS, OMD, LDN, and CMR provided patients’ samples and clinical information. LDN, PLP, and PLM contributed intellectual input and data analysis and revised the manuscript. AV and MB designed research experiments, supervised the study, and reviewed the manuscript. All authors contributed to the article and approved the submitted version.\n\nFunding\n\nThis work was supported by the Italian Telethon Foundation (Telethon Core Grant TGT16F03) to MB. FF was supported by a PhD fellowship at Vita-Salute San Raffaele University (Milan, Italy). LDN is supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.\n\nConflict of Interest\n\nThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\n\nThe handling editor declared a shared affiliation with one of the authors (CRM).\n\nAcknowledgments\n\nWe thank Emanuele Canonico, Daniela Boselli, Simona Di Terlizzi and Chiara Villa of the Flow cytometry Resource, Advanced Cytometry Technical Applications Laboratory (FRACTAL) of San Raffaele Scientific Institute for their help in performing cell sorting. We thank Stefano Zancan and Ambra Corti of Tiget Clinical Trial Office (TCTO) for the biological samples collection protocols. We are grateful to all patients who have participated in this study and their families.\n\nSupplementary Material\n\nThe Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2021.669943/full#supplementary-material\n\nClick here for additional data file.\n\nClick here for additional data file.\n\nClick here for additional data file.\n\nClick here for additional data file.\n\nClick here for additional data file.\n\nClick here for additional data file.\n\nClick here for additional data file.\n\nClick here for additional data file.\n\nClick here for additional data file.\n\nClick here for additional data file.\n\nClick here for additional data file.\n==== Refs\nReferences\n\n1 Reith W Mach B . The Bare Lymphocyte Syndrome and the Regulation of MHC Expression. Annu Rev Immunol (2001) 19 :331–73. 10.1146/annurev.immunol.19.1.331\n2 Ting JP-Y Trowsdale J . Genetic Control of MHC Class II Expression. Cell (2002) 109 :S21–33.  10.1016/S0092-8674(02)00696-7\n3 Nekrep N Fontes JD Geyer M Peterlin BM . When the Lymphocyte Loses Its Clothes. Immunity (2003) 18 :453–7.  10.1016/S1074-7613(03)00086-4\n4 Hanna S Etzioni A . MHC Class I and II Deficiencies. J Allergy Clin Immunol (2014) 134 :269–75.  10.1016/j.jaci.2014.06.001\n5 Klein C Lisowska-Grospierre B LeDeist F Fischer A Griscelli C . Major Histocompatibility Complex Class II Deficiency: Clinical Manifestations, Immunologic Features, and Outcome. J Pediatr (1993) 123 :921–8. 10.1016/S0022-3476(05)80388-9\n6 Villard J Masternak K Lisowska-Grospierre B Fischer A Reith W . MHC Class II Deficiency: A Disease of Gene Regulation. Med (2001) 80 :405–18. 10.1097/00005792-200111000-00006\n7 Lev A Simon AJ Broides A Levi J Garty BZ Rosenthal E . Thymic Function in MHC Class II-Deficient Patients. J Allergy Clin Immunol (2013) 131 :831–9.  10.1016/j.jaci.2012.10.040\n8 Schuurman HJ van de Wijngaert FP Huber J Schuurman RKB Zegers BJM Roord JJ . The Thymus in “Bare Lymphocyte” Syndrome: Significance of Expression of Major Histocompatibility Complex Antigens on Thymic Epithelial Cells in Intrathymic T-Cell Maturation. Hum Immunol (1985) 13 :69–82.  10.1016/0198-8859(85)90014-X 3874194\n9 Ochs H Edvard Smith C Puck JM . Primary Immunodeficiency Diseases – A Molecular and Genetic Approach. 3rd ed. New York: Oxford University Press (2014).\n10 Lum SH Neven B Slatter MA Gennery AR . Hematopoietic Cell Transplantation for MHC Class II Deficiency. Front Pediatr (2019) 7 :516.  10.3389/fped.2019.00516 31921728\n11 Elhasid R Etzioni A . Major Histocompatibility Complex Class II Deficiency: A Clinical Review. Blood Rev (1996) 10 :242–8. 10.1016/S0268-960X(96)90008-9\n12 Posovszky C Sirin M Jacobsen E Lorenz M Schwarz K Schmidt-Choudhury A . Persisting Enteropathy and Disturbed Adaptive Mucosal Immunity Due to MHC Class II Deficiency. Clin Immunol (2019) 203 :125–33.  10.1016/j.clim.2019.04.012\n13 Saleem MA Arkwright PD Davies EG Cant AJ Veys PA . Clinical Course of Patients With Major Histocompatibility Complex Class II Deficiency. Arch Dis Child (2000) 83 :356–9.  10.1136/adc.83.4.356\n14 Renella R Picard C Neven B Ouachée-Chardin M Casanova JL Le Deist F . Human Leucocyte Antigen-Identical Haematopoietic Stem Cell Transplantation in Major Histocompatiblity Complex Class II Immunodeficiency: Reduced Survival Correlates With an Increased Incidence of Acute Graft-Versus-Host Disease and Pre-Existing Viral Infec. Br J Haematol (2006) 134 :510–6.  10.1111/j.1365-2141.2006.06213.x\n15 Ouederni M Vincent QB Frange P Touzot F Scerra S Bejaoui M . Major Histocompatibility Complex Class II Expression Deficiency Caused by a RFXANK Founder Mutation: A Survey of 35 Patients. Blood (2011) 118 :5108–18.  10.1182/blood-2011-05-352716\n16 Lum SH Anderson C McNaughton P Engelhardt KR MacKenzie B Watson H . Improved Transplant Survival and Long-Term Disease Outcome in Children With MHC Class II Deficiency. Blood (2020) 135 :954–73.  10.1182/blood.2019002690\n17 Cosgrove D Gray D Dierich A Kaufman J Lemeur M Benoist C . Mice Lacking MHC Class II Molecules. Cell (1991) 66 :1051–66. 10.1016/0092-8674(91)90448-8\n18 Grusby MJ Johnson RS Papaioannou VE Glimcher LH . Depletion of CD4+ T Cells in Major Histocompatibility Complex Class II-Deficient Mice. Science (1991) 253 :1417–20. 10.1126/science.1910207\n19 Vanhecke D Verhasselt B De Smedt M De Paepe B Leclercq G Plum J . MHC Class II Molecules Are Required for Initiation of Positive Selection But Not During Terminal Differentiation of Human CD4 Single Positive Thymocytes. J Immunol (1997) 158 :3730–7.\n20 Cardell S Tangri S Chan S Kronenberg M Benoist C Mathis D . CD1-Restricted CD4+ T Cells in Major Histocompatibility Complex Class II-Deficient Mice. J Exp Med (1995) 182 :993–1004. 10.1084/jem.182.4.993 7561702\n21 Waldburger JM Rossi S Hollander GA Rodewald HR Reith W Acha-Orbea H . Promoter IV of the Class II Transactivator Gene Is Essential for Positive Selection of CD4+ T Cells. Blood (2003) 101 :3550–9.  10.1182/blood-2002-06-1855\n22 Nasreen M Ueno T Saito F Takahama Y . In Vivo Treatment of Class II MHC-Deficient Mice With Anti-TCR Antibody Restores the Generation of Circulating Cd4 T Cells and Optimal Architecture of Thymic Medulla. J Immunol (2003) 171 :3394–400.  10.4049/jimmunol.171.7.3394\n23 Irla M Guerri L Guenot J Sergé A Lantz O Liston A . Antigen Recognition by Autoreactive CD4+ Thymocytes Drives Homeostasis of The Thymic Medulla. PloS One (2012) 7 :1–12.  10.1371/journal.pone.0052591\n24 Irla M Hugues S Gill J Nitta T Hikosaka Y Williams IR . Autoantigen-Specific Interactions With CD4+Thymocytes Control Mature Medullary Thymic Epithelial Cell Cellularity. Immunity (2008) 29 :451–63.  10.1016/j.immuni.2008.08.007\n25 Bochtler P Wahl C Schirmbeck R Reimann J . Functional Adaptive CD4 Foxp3 T Cells Develop in MHC Class II-Deficient Mice. J Immunol (2006) 177 :8307–14.  10.4049/jimmunol.177.12.8307\n26 Krajina T Leithäuser F Reimann J . MHC Class II-independent Cd25+ CD4+ Cd8α β+ αβ T Cells Attenuate CD4+ T Cell-Induced Transfer Colitis. Eur J Immunol (2004) 34 :705–14.  10.1002/eji.200324463\n27 Bienvenu B Martin B Auffray C Cordier C Becourt C Lucas B . Peripheral CD8+CD25+ T Lymphocytes From MHC Class II-Deficient Mice Exhibit Regulatory Activity. J Immunol (2005) 175 :246–53.  10.4049/jimmunol.175.1.246\n28 Comans-Bitter WM de Groot R van den Beemd R Neijens HJ Hop WC Groeneveld K . Immunophenotyping of Blood Lymphocytes in Childhood. Reference Values for Lymphocyte Subpopulations. J Pediatr (1997) 130 :388–93. 10.1016/S0022-3476(97)70200-2\n29 Bray NL Pimentel H Melsted P Pachter L . Near-Optimal Probabilistic RNA-seq Quantification. Nat Biotechnol (2016) 34 :525–7.  10.1038/nbt.3519\n30 Love MI Huber W Anders S . Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data With Deseq2. Genome Biol (2014) 15 :1–21.  10.1186/s13059-014-0550-8\n31 Keane P Ceredig R Seoighe C . Promiscuous mRNA Splicing Under the Control of AIRE in Medullary Thymic Epithelial Cells. Bioinformatics (2015) 31 :986–90.  10.1093/bioinformatics/btu785\n32 Berland A Rosain J Kaltenbach S Allain V Mahlaoui N Melki I . Promidisα: A T-Cell Receptor α Signature Associated With Immunodeficiencies Caused by V(D)J Recombination Defects. J Allergy Clin Immunol (2019) 143 :325–34.  10.1016/j.jaci.2018.05.028\n33 Sansom SN Shikama-Dorn N Zhanybekova S Nusspaumer G Macaulay IC Deadman ME . Population and Single-Cell Genomics Reveal the Aire Dependency, Relief From Polycomb Silencing, and Distribution of Self-Antigen Expression in Thymic Epithelia. Genome Res (2014) 24 :1918–31.  10.1101/gr.171645.113\n34 Danan-Gotthold M Guyon C Giraud M Levanon EY Abramson J . Extensive RNA Editing and Splicing Increase Immune Self-Representation Diversity in Medullary Thymic Epithelial Cells. Genome Biol (2016) 17 :1–13.  10.1186/s13059-016-1079-9 26753840\n35 Ostanin DV Bao J Koboziev I Gray L Robinson-Jackson SA Kosloski-Davidson M . T Cell Transfer Model of Chronic Colitis: Concepts, Considerations, and Tricks of the Trade. Am J Physiol Gastrointest Liver Physiol (2009) 296 :G135–46.  10.1152/ajpgi.90462.2008\n36 Arismendi M Kallas E Santos B Carneiro-Sampaio M Kayser C . Thymopoiesis and Regulatory T Cells in Healthy Children and Adolescents. Clinics (2012) 67 :425–9.  10.6061/clinics/2012(05)04\n37 Rosenberg JM Utz PJ . Protein Microarrays: A New Tool for the Study of Autoantibodies in Immunodeficiency. Front Immunol (2015) 6 :138.  10.3389/fimmu.2015.00138 25904912\n38 Cancro MP . Signalling Crosstalk in B Cells: Managing Worth and Need. Nat Rev Immunol (2009) 9 :657–61. 10.1038/nri2621\n39 Rowland SL Leahy KF Halverson R Torres RM Pelanda R . Baff Receptor Signaling Aids the Differentiation of Immature B Cells Into Transitional B Cells Following Tonic BCR Signaling. J Immunol (2010) 185 :4570–81.  10.4049/jimmunol.1001708\n40 Abramson J Goldfarb Y . Aire: From Promiscuous Molecular Partnerships to Promiscuous Gene Expression. Eur J Immunol (2016) 46 :22–3.  10.1002/eji.201545792\n41 Herzig Y Nevo S Bornstein C Brezis MR Ben-Hur S Shkedy A . Transcriptional Programs That Control Expression of the Autoimmune Regulator Gene Aire. Nat Immunol (2017) 18 :161–72.  10.1038/ni.3638\n42 Chuprin A Avin A Goldfarb Y Herzig Y Levi B Jacob A . The Deacetylase Sirt1 Is An Essential Regulator of Aire-Mediated Induction of Central Immunological Tolerance. Nat Immunol (2015) 16 :737–45.  10.1038/ni.3194\n43 Akiyama T Shimo Y Yanai H Qin J Ohshima D Maruyama Y . The Tumor Necrosis Factor Family Receptors RANK and CD40 Cooperatively Establish the Thymic Medullary Microenvironment and Self-Tolerance. Immunity (2008) 29 :423–37.  10.1016/j.immuni.2008.06.015\n44 Lopes N Sergé A Ferrier P Irla M . Thymic Crosstalk Coordinates Medulla Organization and T-Cell Tolerance Induction. Front Immunol (2015) 6 :365.  10.3389/fimmu.2015.00365 26257733\n45 Lo Iacono N Blair HC Poliani PL Marrella V Ficara F Cassani B . Osteopetrosis Rescue Upon RANKL Administration to Rankl-/- Mice: A New Therapy for Human RANKL-Dependent Aro. J Bone Miner Res (2012) 27 :2501–10.  10.1002/jbmr.1712\n46 Lopes N Vachon H Marie J Irla M . Administration of RANKL Boosts Thymic Regeneration Upon Bone Marrow Transplantation. EMBO Mol Med (2017) 9 :835–51.  10.15252/emmm.201607176\n47 Matheux F Villard J . Cellular and Gene Therapy for Major Histocompatibility Complex Class II Deficiency. Physiology (2004) 19 :154–8.  10.1152/nips.01462.2003\n48 Legoux FP Lim JB Cauley AW Dikiy S Ertelt J Mariani TJ . CD4+ T Cell Tolerance to Tissue-Restricted Self Antigens Is Mediated by Antigen-Specific Regulatory T Cells Rather Than Deletion. Immunity (2015) 43 :896–908.  10.1016/j.immuni.2015.10.011 26572061\n49 Aschenbrenner K D’Cruz LM Vollmann EH Hinterberger M Emmerich J Swee LK . Selection of Foxp3+Regulatory T Cells Specific for Self Antigen Expressed and Presented by Aire+Medullary Thymic Epithelial Cells. Nat Immunol (2007) 8 :351–8.  10.1038/ni1444\n50 Wirnsberger G Hinterberger M Klein L . Regulatory T-Cell Differentiation Versus Clonal Deletion of Autoreactive Thymocytes. Immunol Cell Biol (2011) 89 :45–53. 10.1038/icb.2010.123 21042335\n51 Cowan JE Parnell SM Nakamura K Caamano JH Lane PJL Jenkinson EJ . The Thymic Medulla is Required for Foxp3 + Regulatory But Not Conventional CD4 + Thymocyte Development. J Exp Med (2013) 210 :675–81.  10.1084/jem.20122070\n52 Hervé M Isnardi I Ng Y Bussel JB Ochs HD Cunningham-Rundles C . CD40 Ligand and MHC Class II Expression Are Essential for Human Peripheral B Cell Tolerance. J Exp Med (2007) 204 :1583–93.  10.1084/jem.20062287\n53 Kreuzaler M Rauch M Salzer U Birmelin J Rizzi M Grimbacher B . Soluble BAFF Levels Inversely Correlate With Peripheral B Cell Numbers and the Expression of BAFF Receptors. J Immunol (2012) 188 :497–503.  10.4049/jimmunol.1290009 22124120\n54 Groom J Kalled SL Cutler AH Olson C Woodcock SA Schneider P . Association of BAFF/BLyS Overexpression and Altered B Cell Differentiation With Sjögren’s Syndrome. J Clin Invest (2002) 109 :59–68.  10.1172/JCI0214121 11781351\n55 Becker-Merok A Nikolaisen C Nossent H . B-Lymphocyte Activating Factor in Systemic Lupus Erythematosus and Rheumatoid Arthritis in Relation to Autoantibody Levels, Disease Measures and Time. Lupus (2006) 15 :570–6. 10.1177/0961203306071871\n56 Fontaine J Chagnon-Choquet J Valcke H Poudrier J Roger M Groups MPHI . And L-TN-PS. High Expression Levels of B Lymphocyte Stimulator (BlyS) by Dendritic Cells Correlate With HIV-Related B-Cell Disease Progression in Humans. Blood (2011) 117 :145–55. 10.1182/blood-2010-08-301887\n57 Coquery CM Wade NS Loo WM Kinchen JM Cox KM Jiang C . Neutrophils Contribute to Excess Serum BAFF Levels and Promote CD4+ T Cell and B Cell Responses in Lupus-Prone Mice. PloS One (2014) 9 :e102284.  10.1371/journal.pone.0102284 25010693\n58 Sutherland A Ng L Fletcher C Shum B Newton R Grey S . BAFF Augments Certain Th1-Associated Inflammatory Responses. J Immunol (2005) 174 :5537–44.  10.4049/jimmunol.174.9.5537\n59 Sasaki Y Derudder E Hobeika E Pelanda R Reth M Rajewsky K . Canonical NF-κb Activity, Dispensable for B Cell Development, Replaces BAFF-Receptor Signals and Promotes B Cell Proliferation Upon Activation. Immunity (2006) 24 :729–39.  10.1016/j.immuni.2006.04.005\n\n", "fulltext_license": "CC BY", "issn_linking": "1664-3224", "issue": "12()", "journal": "Frontiers in immunology", "keywords": "MHCII; central tolerance; primary immunodeficiency; thymic epithelial cells; thymus", "medline_ta": "Front Immunol", "mesh_terms": "D000293:Adolescent; D000818:Animals; D001402:B-Lymphocytes; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D004847:Epithelial Cells; D005060:Europe; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009656:North America; D020543:Proteome; D016511:Severe Combined Immunodeficiency; D050378:T-Lymphocytes, Regulatory; D060168:Thymocytes; D013950:Thymus Gland; D059467:Transcriptome; D055815:Young Adult", "nlm_unique_id": "101560960", "other_id": null, "pages": "669943", "pmc": null, "pmid": "34211466", "pubdate": "2021", "publication_types": "D016428:Journal Article; D016448:Multicenter Study; D052060:Research Support, N.I.H., Intramural; D013485:Research Support, Non-U.S. Gov't", "references": "23300712;1909605;3874194;9012922;16848795;12506036;25001848;1910207;25224068;15143213;17080911;22124120;26006015;20861359;15972655;11983150;22836362;25516281;27043002;23530124;8229525;18799149;19033538;17322887;31028919;28455312;25429061;21908431;26450177;11704716;16782029;31921728;29906526;15843552;10999878;26257733;31932845;27776542;12705848;25904912;21042335;17562816;7561702;23228244;20870901;11244040;22666784;25010693;9103437;14500633;19704418;11781351;26572061;14991600;17142726;9063413;27941786;18799151", "title": "Thymic Epithelial Cell Alterations and Defective Thymopoiesis Lead to Central and Peripheral Tolerance Perturbation in MHCII Deficiency.", "title_normalized": "thymic epithelial cell alterations and defective thymopoiesis lead to central and peripheral tolerance perturbation in mhcii deficiency" }

[ { "companynumb": "IT-OTSUKA-2021_045444", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BUSULFAN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "020954", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Allogenic stem cell transplantation", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUSULFAN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "BUSULFAN" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "020954", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Bone marrow conditioning regimen", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUSULFAN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "FLUDARABINE PHOSPHATE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Allogenic stem cell transplantation", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUDARABINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "FLUDARABINE PHOSPHATE" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Bone marrow conditioning regimen", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUDARABINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Allogenic stem cell transplantation", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Bone marrow conditioning regimen", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LAPINE T-LYMPHOCYTE IMMUNE GLOBULIN" } ], "patientagegroup": "2", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Death", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Respiratory failure", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ferrua F, Bortolomai I, Fontana E, Di Silvestre D, Rigoni R, Marcovecchio GE et al. Thymic Epithelial Cell Alterations and Defective Thymopoiesis Lead to Central and Peripheral Tolerance Perturbation in MHCII Deficiency. Frontiers in Immunology. 2021;12:NIL_0001-NIL_0020", "literaturereference_normalized": "thymic epithelial cell alterations and defective thymopoiesis lead to central and peripheral tolerance perturbation in mhcii deficiency", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20220107", "receivedate": "20211228", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20237658, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220424" }, { "companynumb": "IT-OTSUKA-2021_045551", "fulfillexpeditecriteria": "1", "occurcountry": "IT", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "BUSULFAN" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": "020954", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Immunodeficiency", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUSULFAN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "BUSULFAN" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "020954", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Bone marrow conditioning regimen", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUSULFAN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "BUSULFAN" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": "020954", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Injection", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Stem cell transplant", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUSULFAN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "FLUDARABINE PHOSPHATE" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Immunodeficiency", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUDARABINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "FLUDARABINE PHOSPHATE" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Bone marrow conditioning regimen", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUDARABINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "FLUDARABINE PHOSPHATE" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Stem cell transplant", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUDARABINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "THIOTEPA" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Immunodeficiency", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THIOTEPA" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "THIOTEPA" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Bone marrow conditioning regimen", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THIOTEPA" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "THIOTEPA" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Stem cell transplant", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THIOTEPA" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ALEMTUZUMAB" }, "drugadditional": "4", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Immunodeficiency", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALEMTUZUMAB" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ALEMTUZUMAB" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Bone marrow conditioning regimen", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALEMTUZUMAB" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ALEMTUZUMAB" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Stem cell transplant", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ALEMTUZUMAB" } ], "patientagegroup": null, "patientonsetage": "16", "patientonsetageunit": "801", "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Death", "reactionmeddraversionpt": "24.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Venoocclusive disease", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cytopenia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Ferrua F, Bortolomai I, Fontana E, Di Silvestre D, Rigoni R, Marcovecchio GE et al. Thymic Epithelial Cell Alterations and Defective Thymopoiesis Lead to Central and Peripheral Tolerance Perturbation in MHCII Deficiency. Frontiers in Immunology. 2021;12:NIL_0001-NIL_0020", "literaturereference_normalized": "thymic epithelial cell alterations and defective thymopoiesis lead to central and peripheral tolerance perturbation in mhcii deficiency", "qualification": "3", "reportercountry": "IT" }, "primarysourcecountry": "IT", "receiptdate": "20211228", "receivedate": "20211228", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20237655, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 1, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220303" } ]

{ "abstract": "BACKGROUND\nThough respiratory, immune, and coagulation systems are major targets of coronavirus disease 2019 (COVID-19), kidney dysfunction, presenting with acute kidney injury (AKI), is also common. Most AKI cases in COVID-19 manifest as acute tubular injury (ATI) in conjunction with multiorgan failure. While initial renal pathological findings were limited to acute tubular necrosis and collapsing glomerulopathy, a recent case series reported a larger spectrum of findings.\n\n\nMETHODS\nHere, we report a case of membranous nephropathy (MN) in an 81-year-old Hispanic man with underlying chronic kidney disease (CKD) stage 3 who developed ATI in the setting of COVID-19. The patient was hospitalized for hypoxic respiratory failure in the setting of AKI stage 3 with serum creatinine 7.1 mg/dL 6 days after a positive-SARS-CoV-2 screening. He was found to have nephrotic range proteinuria, glycosuria (with normal serum glucose), anemia, and hypoalbuminemia. Kidney biopsy showed ATI and early MN. Workup for primary and secondary MN was unrevealing, and serum PLA2R antibody was negative. No viral particles were observed in podocytes.\n\n\nCONCLUSIONS\nAlthough the MN could be incidental, this observation raises the question of whether SARS-CoV-2 infection can trigger or worsen an underlying MN from an exaggerated immune response associated with COVID-19.", "affiliations": "Division of Nephrology and Hypertension.;Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, and.;Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, and.;Arkana Laboratories, Little Rock, AR, USA.;Division of Nephrology and Hypertension.", "authors": "Miao|Jing|J|;Fidler|Mary E|ME|;Nasr|Samih H|SH|;Larsen|Christopher P|CP|;Zoghby|Ziad M|ZM|", "chemical_list": null, "country": "Germany", "delete": false, "doi": "10.5414/CNCS110379", "fulltext": "\n==== Front\nClin Nephrol Case Stud\nDustri\nClinical Nephrology. Case Studies\n2196-5293 Dustri-Verlag Dr. Karl Feistle \n\n10.5414/CNCS110379\nCase Report\nNephrology\nMembranous nephropathy in a patient with coronavirus disease 2019 (COVID-19): A case report \nMiao Jing 1 Fidler Mary E. 2 Nasr Samih H. 2 Larsen Christopher P. 3 Zoghby Ziad M. 1 1 Division of Nephrology and Hypertension, \n2 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, and \n3 Arkana Laboratories, Little Rock, AR, USA\nCorrespondence to: Ziad M. Zoghby, MD, FACP Assistant Professor of Medicine Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA zoghby.ziad@mayo.edu\n2021 \n19 2 2021 \n9 11 18\n8 9 2020 10 11 2020 © Dustri-Verlag Dr. K. Feistle2021 This is an open-access article distributed under the terms of the Creative\nCommons Attribution License, which permits unrestricted use, distribution, and\nreproduction in any medium, provided the original work is properly cited.Introduction: Though respiratory, immune, and coagulation systems are major targets of coronavirus disease 2019 (COVID-19), kidney dysfunction, presenting with acute kidney injury (AKI), is also common. Most AKI cases in COVID-19 manifest as acute tubular injury (ATI) in conjunction with multiorgan failure. While initial renal pathological findings were limited to acute tubular necrosis and collapsing glomerulopathy, a recent case series reported a larger spectrum of findings. Case report: Here, we report a case of membranous nephropathy (MN) in an 81-year-old Hispanic man with underlying chronic kidney disease (CKD) stage 3 who developed ATI in the setting of COVID-19. The patient was hospitalized for hypoxic respiratory failure in the setting of AKI stage 3 with serum creatinine 7.1 mg/dL 6 days after a positive-SARS-CoV-2 screening. He was found to have nephrotic range proteinuria, glycosuria (with normal serum glucose), anemia, and hypoalbuminemia. Kidney biopsy showed ATI and early MN. Workup for primary and secondary MN was unrevealing, and serum PLA2R antibody was negative. No viral particles were observed in podocytes. Conclusion: Although the MN could be incidental, this observation raises the question of whether SARS-CoV-2 infection can trigger or worsen an underlying MN from an exaggerated immune response associated with COVID-19. \n\nacute kidney injury (AKI)coronavirus disease 2019 (COVID-19)membranous nephropathy (MN)renal pathologySRAS-CoV-2\n==== Body\nIntroduction \nCoronavirus disease 2019 (COVID-19), caused by a coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread worldwide since December 2019 [1].The principle feature of COVID-19 is viral pneumonia, leading to acute respiratory distress syndrome (ARDS) [2]. Similar to other coronaviruses, angiotensin-converting enzyme 2 (ACE2) may play a major role in the entry of SARS-CoV-2 to its target cells [3]. Besides the respiratory system, ACE2 is also highly expressed in the brush border of proximal tubular cells and, to a lesser extent, in glomerular podocytes [4]. Kidney involvement of COVID-19, mainly presents as acute kidney injury (AKI) [5], primarily due to acute tubular injury (ATI) in the setting of multiorgan failure. Clinically, the incidence of AKI in COVID-19 varies from 0.9 to 29% in hospitalized or critically ill patients at different centers [6, 7, 8] and is associated with worse outcomes [5, 9]. ATI and direct parenchymal infection of tubular epithelial cells and podocytes were reported in 26 postmortem examinations of patients with severe COVID-19 [10]. Proteinuria and hematuria are also common, occurring in 44 and 27%, respectively [5]. Kidney biopsy findings have been reported initially in four living COVID-19 cases, all of which showed collapsing glomerulopathy [11, 12, 13, 14]. Recently, two case series of kidney biopsy findings showed that ATI was the most common finding in COVID-19-associated kidney injury, but the series by Kudose et al. [15, 16] reported a wide spectrum of glomerular and tubular disease including minimal change disease and membranous glomerulopathy. Here, we report a case of membranous nephropathy (MN) diagnosed in the setting of AKI associated with COVID-19. \n\nCase report \nAn 81-year-old Hispanic man presented to the emergency department complaining of progressive fatigue and shortness of breath 6 days after being diagnosed with COVID-19 (positive nasopharyngeal SARS-CoV-2 PCR). He reported myalgia, sore throat, intermittent dry cough, loss of smell and taste, poor appetite, and nausea without vomiting. He also had diarrhea and an episode of urinary incontinence. He denied fever or chills, chest pain, and headache. Because of hypoxemia requiring high-flow oxygen, the patient was admitted to the critical care unit. \n\nPrevious medical history includes prostate cancer treated with chemotherapy and androgen deprivation therapy in 2013, in remission with undetectable prostate-specific antigen (PSA) since 2014, prediabetes, hyperlipidemia, hypertension, chronic kidney disease (CKD) stage 3 (baseline creatinine 1.2 – 1.6 mg/dL) attributed to hypertension with prior urine analysis in 2017 showing proteinuria of 385 mg/day, aortic valve stenosis, and cervical radiculopathy. Home medications included olmesartan 20 mg twice daily and hydrochlorothiazide 12.5 mg daily. Notably, he had a history of non-steroidal anti-inflammatory drugs (NSAIDs) use, 400 – 800 mg of ibuprofen per day for chronic neck pain. He is a former smoker but quit in 2012 and did not have lung disease. \n\nInitial vital signs: temperature 37.4 °C, blood pressure 166/69 mmHg, heart rate 68 beats per minute, respiratory rate 27 breaths per minute, and peripheral capillary oxygen saturation (SpO2) 95% on high-flow nasal cannula (50 L/min with FiO2 of 100%). Physical examination was notable for tachypnea with the remainder of physical examination unremarkable. \n\n\nTable 1 and Table 2 show his laboratory results. Repeat SARS-CoV-2 PCR via nasopharyngeal swab was positive. He had evidence of AKI stage 3 with a serum creatinine of 7.1 mg/dL. Urinalysis demonstrated 3 – 10 red blood cells per high power field, nephrotic range proteinuria of 4.6 g per 24 hours, glycosuria, and tubular epithelial cells. He had anemia with hemoglobin of 10.3 g/dL, hypoalbuminemia of 1.7 g/dL, and multiple elevated inflammatory markers, including interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and ferritin. Kidney ultrasound revealed bilaterally increased parenchymal echogenicity consistent with CKD. Chest radiograph showed indistinct pulmonary vasculature bilaterally with bronchocentric ground glass, and bilateral patchy infiltrates, consistent with COVID-19 pneumonia. Lower extremities Doppler did not reveal deep vein thromboses, and transthoracic echocardiogram was normal. \n\nHe was enrolled in a randomized placebo-controlled clinical trial of lenzilumab (monoclonal antibody targeting GM-CSF) 600 mg for 3 doses, in addition to intravenous antibiotics for possible superimposed community-acquired pneumonia. He completed a steroid trial with 5 days of intravenous methylprednisolone. Due to increasing D-dimer to 100,000 ng/mL, low-intensity heparin infusion was initiated. \n\nOver the first few hospitalization days, creatinine remained elevated at ~ 7 mg/dL. He did not require dialysis as he maintained excellent urine output. Serologic testing for hepatitis B, hepatitis C, human immunodeficiency virus (HIV), tuberculosis, as well as C3, C4, anti-neutrophil cytoplasmic antibodies (ANCA), anti-glomerular basement membrane (GBM), and anti-phospholipase A2 receptors (PLA2R) were all negative. Anti-THSD7A was indeterminate due to high background. No serum monoclonal proteins were detected. Kidney biopsy was performed on hospital day 4. \n\nOn hospital day 7, the patient’s respiratory status worsened requiring intubation, mechanical ventilation, and initiation of vasopressors. Despite that, his AKI was slowly recovering and creatinine reached 3.7 mg/dL on hospital day 11. However, the shock state subsequently worsened, continuous dialysis was started but eventually the patient died on hospital day 16. Family declined an autopsy. \n\nKidney pathology findings \n19 glomeruli were sampled for light microscopy, 8 of which were globally sclerotic and 1 was segmentally sclerotic. The glomeruli showed segmental mild mesangial hypercellularity and mesangial expansion, with thickening of their basement membranes (Figure 1A). No collapsing features, endocapillary hypercellularity, thrombi, necrosis, or crescents were seen. The tubulointerstitial compartment exhibited diffuse ATI, tubular protein reabsorption granules, mild tubular atrophy and interstitial fibrosis, and very mild mononuclear cell infiltrate without tubulitis. There was moderate arteriosclerosis and arteriolar hyalinosis. \n\nImmunofluorescence studies were unable to be performed due to an inadequate sample. Immunohistochemistry staining for PLA2R was performed on sections prepared from the paraffin block and was negative. \n\nIn situ hybridization (ISH) staining for the presence of SARS-CoV-2 RNA was performed using RNAScope (ACD, Newark, CA, USA) and failed to show evidence of viral RNA in the kidney (methods in Supplemental Material). \n\nElectron microscopy showed abundant small granular sub-epithelial electron-dense deposits without or associated with early basement membrane spike formation (Figure 1B). The glomerular basement membrane lamina densa was thickened. There was mild mesangial sclerosis with segmental mesangial electron-dense deposits, without sub-endothelial deposits. Abundant tubuloreticular inclusion bodies were seen in the endothelial cell cytoplasm (Figure 1C). Podocytes exhibited severe foot process effacement. \n\nThe pathological diagnosis was MN (stage 1 to early stage 2), diffuse ATI, mild mesangial sclerosing glomerulopathy (associated with hypertension, pre-diabetes, and smoking), and moderate arteriosclerosis and arteriolar hyalinosis. \n\nDiscussion \nTo our knowledge, MN diagnosed in a patient with COVID-19 has been reported in only 2 patients in one case series of 17 patients [16]. The finding of severe ATI in this case is not surprising as reported in recent series of COVID-19 patients [10, 15]. However, the finding of MN was unexpected. \n\nMN, an inflammatory and autoimmune disease of the glomerulus, is one of the most common causes of nephrotic syndrome in adults. The etiology of ~ 75% of MN is unknown “primary”. Secondary MN can be secondary to infection, drugs, and malignancy [18]. Thus, the main question is whether the MN in this case is related to SARS-CoV-2 or not. This patient had a history of prostate cancer, but he was in remission for at least 6 years with normal PSA, so it is unlikely that his cancer was the underlying cause of the MN. NSAIDs can cause proteinuria and have been associated with minimal change disease as well as MN, but the patient did not have prior evidence of nephrotic syndrome despite being on NSAIDs for many years. The absence of detectable anti-PLA2R antibodies, the negative glomerular staining for PLA2R and the presence of mesangial deposits, as well as abundant tubuloreticular inclusions favor secondary MN over primary MN. The patient had mild proteinuria (385 mg/day) prior to COVID-19 which is likely due to underlying mild mesangial sclerosing glomerulopathy (associated with hypertension, prediabetes, and smoking). MN was mostly stage 1 favoring a recent development of disease temporally associated with COVID-19 over pre-existing MN. \n\nThe pathogenesis of MN involves formation and deposition of immune complexes in sub-epithelial sites [18]. The receptor for SARS-CoV-2, ACE2, is highly expressed on proximal tubular cells and glomerular podocytes [4]. In addition, TMPRSS2, an essential serine protease, is required for spike glycoprotein of SARS-CoV-2 priming after binding to ACE2, and thus activates membrane fusion facilitating to gain access to its target cells [19]. In kidneys, expression of TMPRSS2 is only detectable in the proximal tubule S3 segment [20]. An in vitro study showed that the administration of TMPRSS2 inhibitor, camostat mesylate, had a valuable treatment effect, blocking multiple SARS-CoV-2 entry routes [21]. In postmortem kidney samples, SARS-CoV-2 antigens and viral particles were detected in the tubular epithelium and podocytes [10, 17]. In the case of collapsing glomerulopathy associated with COVID-19 reported by Kissling et al. [13], the virus was seen in podocytes by electron microscopy. However, most recent biopsy series fail to show viral particles in kidney biopsies by immunohistochemistry staining or by electron microscopy arguing against a direct viral infection of the kidneys [15, 16]. Similarly, in this case we did not find evidence of viral particles in the kidneys. Rather than a direct toxic viral effect on the kidneys, the ATI is most likely cytokine mediated, although the NSAID, angiotensin receptor blocker, and diuretic exposures could also have contributed. Whether MN can be secondary to SARS-CoV-2 remains to be elucidated, but we speculate that it could result from an exaggerated immune response associated with COVID-19. In the passive Heymann nephritis model, sub-epithelial deposits with very early basement membrane reaction could be seen as early as 7 days after injection [22]. Therefore, we hypothesize that the development of MN deposits could possibly occur quickly after a viral infection, or alternatively the COVID-19-related immune response and the resulting high-grade proteinuria could unmask an underlying MN. If this is the case, the treatment of this patient’s MN is conservative and immunosuppressive therapy is not recommended. \n\nFunding \nNone. \n\nConflict of interest \nThe authors declare no relevant financial interest. \n\nSupplemental material \nISH methods \nIn situ hybridization was performed with RNAScope (ACD, Newark, CA) using probes directed against SARS-CoV-2 on formalin-fixed paraffin-embedded tissue sections cut at a thickness of 3 microns. 1A negative control (bacterial gene dapB) was also included to assess background signals as well as positive control probes to the housekeeping gene peptidylprolyl isomerase B (PPIB). The ISH sections were counterstained using periodic acid-Schiff. (Wang F, Flanagan J, Su N, Wang LC, Bui S, Nielson A, et al. RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. J Mol Diagn. 2012; 14: 22-29). \n\n\nTable 1. Laboratory data. \nLaboratory test\t1 year before \nadmission\tDay 1\tDay 4 \n(Kidney biopsy)\tDay 7\tReference\t\nArterial blood gas\t\n   pH\t\t7.43\t7.36\t7.29\t7.35 – 7.45\t\n   pCO2, mmHg\t\t23\t27\t38\t32 – 45\t\n   pO2, mmHg\t\t137\t68\t72\t83 – 108\t\n   HCO3\n-, mmol/L\t\t15\t15\t18\t22 – 26\t\nComplete blood count\t\n   WBC count, 109/L\t\t11.2\t15.0\t15.1\t3.4 – 9.6\t\n   Neutrophils, 109/L\t\t10.35\t\t\t1.56 – 6.45\t\n   Lymphocytes, 109/L\t\t0.46\t\t\t0.95 – 3.07\t\n   Erythrocytes, 1012/L\t\t3.37\t3.40\t2.36\t4.35 – 5.65\t\n   Hemoglobin, g/dL\t\t11.3\t11.4\t7.9\t13.2 – 16.6\t\n   Reticulocytes, %\t\t\t\t2.12\t0.6 – 2.71\t\n   Platelet count, 109/L\t\t449\t436\t295\t135 – 317\t\nSerum biochemistry\t\n   Sodium, mmol/L\t\t138\t139\t138\t135 – 145\t\n   Potassium, mmol/L\t\t5.4\t4.5\t4.1\t3.6 – 5.2\t\n   Chloride, mmol/L\t\t100\t99\t103\t98 – 107\t\n   Bicarbonate, mmol/L\t\t17\t17\t19\t22 – 29\t\n   Anion gap\t\t21\t23\t17\t7 – 15\t\n   BUN, mg/dL\t\t98\t133\t128\t8 – 24\t\n   Creatinine, mg/dL\t1.4\t7.05\t6.96\t4.41\t0.74 – 1.35\t\n   eGFR, mL/min/BSA\t49\t< 15\t< 15\t< 15\t> 60\t\n   eGFR by cystatin C, mL/min/BSA\t\t\t6\t\t> 60\t\n   Calcium, total, mg/dL\t\t8.9\t8.3\t8.1\t8.8 – 10.2\t\n   Calcium, ionized, mg/dL\t\t4.40\t4.57\t4.62\t4.65 – 5.30\t\n   Glucose, mg/dL\t\t127\t165\t145\t70 – 140\t\n   Magnesium, mg/dL\t\t\t3.8\t2.9\t1.7 – 2.3\t\n   Phosphorus, mg/dL\t\t\t11.5\t7.9\t2.5 – 4.5\t\n   Total protein, g/dL\t\t4.4\t\t4.5\t6.3 – 7.9\t\n   Albumin, g/dL\t\t1.7\t\t2.6\t3.5 – 5.0\t\n   Hemoglobin A1C, %\t5.9\t\t\t\t4 – 5.6\t\n   Lactate, mmol/L\t\t1.3\t\t1.1\t0.5 – 2.2\t\nLiver function\t\n   ALT, U/L\t45\t36\t\t11\t7 – 55\t\n   AST, U/L\t43\t49\t\t22\t8 – 48\t\n   Bilirubin, total, mg/dL\t0.6\t< 0.2\t\t0.5\t< 1.2\t\n   Bilirubin, direct, mg/dL\t0.3\t< 0.2\t\t0.4\t0.0 – 0.3\t\n   Alkaline protease, U/L\t\t155\t\t70\t40 – 129\t\nLipid/cardiac risk\t\n   Total cholesterol, mg/dL\t241\t\t226\t\t< 200\t\n   HDL, mg/dL\t38\t\t34\t\t≥ 40\t\n   LDL, mg/dL\t153\t\t131\t\t< 100\t\n   Triglycerides, mg/dL\t248\t\t304\t\t< 150\t\n   Troponin T, ng/L\t\t71\t\t160\t< 15\t\n   Troponin T-2h, ng/L\t\t80\t\t153\t< 15\t\n   Troponin T-6h, ng/L\t\t87\t\t152\t< 15\t\n   NT-pro BNP, pg/mL\t220\t5,030\t\t\t5 – 131\t\n   Creatinine kinase, U/L\t\t\t\t108\t39 – 308\t\nCoagulation\t\n   Antithrombin activity\t\t\t91\t\t80 – 130%\t\n   D-dimer, ng/mL\t\t13,286\t> 100,000\t48,550\t< 500\t\n   Fibrinogen, Clauss, mg/dL\t\t\t> 800\t561\t200 – 500\t\n   Coag factor II\t\t\t101\t92\t75 – 145%\t\n   Coag factor V\t\t\t132\t110\t70 – 165%\t\n   Coag factor VII\t\t\t116\t83\t65 – 180%\t\n   Coag factor X\t\t\t131\t86\t70 – 150%\t\n   C-reactive protein, mg/L\t\t> 400\t173.3\t142.1\t< 8\t\n   Soluble fibrin monomer, mcg/mL\t\t\t> 1,100\t36\t≤ 8\t\n   Plasminogen activity\t\t\t98\t\t75 – 140%\t\n   α-2 plasmin inhibitor\t\t\t105\t\t80 – 140%\t\n   Sedimentation rate, mm/h\t\t> 140\t123\t\t3 – 28\t\n   Ferritin, µg/L\t\t1,122\t1,813\t911\t24 – 336\t\nSerology\t\n   HBs antigen\t\tNegative\t\t\tNegative\t\n   HBc total Ab\t\tNegative\t\t\tNegative\t\n   HCV Ab screen\t\tNegative\t\t\tNegative\t\n   HIV-1/-2 Ag and Ab\t\tNegative\t\t\tNegative\t\n   Complement C3, mg/dL\t\t163\t\t\t75 – 175\t\n   Complement C4, mg/dL\t\t36\t\t\t13 – 40\t\n   C-ANCA\t\t\tNegative\t\tNegative\t\n   p-ANCA\t\t\tNegative\t\tNegative\t\n   Anti-GBM, U\t\t\t< 0.2\t\t< 1 (negative)\t\n   Anti-phospholipase A2 receptor (IF)\t\t\tNegative\t\tNegative\t\n   Anti-phospholipase A2 receptor (ELISA), RU/mL\t\t\t< 2\t\t< 14\t\n   Interleukin 6, pg/mL\t\t39.5\t3.5\t5.7\t< 1.8\t\nMonoclonal gammopathy screen\t\n   κ free light chain, mg/dL\t\t\t15.5\t\t0.33 – 1.94\t\n   λ free light chain, mg/dL\t\t\t8.73\t\t0.57 – 2.63\t\n   κ/λ ratio\t\t\t1.78\t\t0.26 – 1.65\t\n   Total protein, g/dL\t\t\t5.3\t\t6.3 – 7.9\t\n   Albumin, g/dL\t\t\t1.4\t\t3.4 – 4.7\t\n   α-1 globulin, g/dL\t\t\t0.6\t\t0.1 – 0.3\t\n   α 2-globulin, g/dL\t\t\t1.5\t\t0.6 – 1.0\t\n   β globulin, g/dL\t\t\t1.0\t\t0.7 – 1.2\t\n   γ globulin, g/dL\t\t\t0.8\t\t0.6 – 1.6\t\n   A/G ratio\t\t\t0.36\t\t\t\n   M protein isotype\t\t\tCannot rule out small monoclonal protein\t\t\t\nEndocrine\t\n   TSH, mIU/L\t1.1\t\t\t0.2\t0.3 – 4.2\t\n   T4 (thyroxine), ng/dL\t\t\t\t1.3\t0.9 – 1.7\t\n   PTH, pg/mL\t\t231\t\t\t15 – 65\t\nTumor/malignancy marker\t\n   Prostate specific Ag, ng/mL\t0.21\t0.15\t\t\t≤ 7.2\t\n\n\n\n\nTable 2. Urinalysis data. \nLaboratory test\t3 years prior to admission\tOn admission\tDay 2\tReference range\t\nSource\tMidstream\tCatheter\tCatheter\t\t\nAppearance\tNormal\tNormal\tNormal\t\t\nOsmolality, mOsm/kg\t\t372\t339\t150 – 1150\t\npH\t\t5.2\t5.5\t4.5 – 8.0\t\nGlucose, mg/dL\t5\t81\t12\t0 – 15\t\nProtein, mg/dL\t17\t339\t117\t< 26\t\nProtein/Osmolality, ratio\t0.39\t9.11\t3.45\t< 0.42\t\nPredicted 24 h protein, mg\t385\t7,735\t3,066\t\t\n24-h urine protein, mg/24 h\t\t\t4,662\t< 229\t\nHemoglobin\tNegative\tTrace\tModerate\tNegative\t\nRed blood cell\t\t\t3 – 10\t< 3/HPF\t\nDysmorphic RBC (%)\t\t\t< 25\t< 25\t\nWhite blood cell\t\t1 – 3\t1 – 3\t1 – 3/HPF\t\nCasts, hyaline\t1 – 3\t\tOccasional\t\t\nCasts, granular\t\t\tOccasional\t\t\nFat, free\t\tOccasional\tOccasional\t\t\nFat, in casts\t\t\tOccasional\t\t\nOval fat body\t\t\tOccasional\t\t\nRenal epithelial cells\t\t1 – 3\t\tNone seen/HPF\t\nKetones\t\tNegative\t\tNegative\t\nNitrite\t\tNegative\t\tNegative\t\nLeukocyte\t\tNegative\t\tNegative\t\n\n\n\nFigure 1. Renal pathologic findings in this COVID-19 patient. A: Glomerulus showing thickening of the glomerular basement membrane with mild mesangial sclerosis and hypercellularity (silver stain, × 400). B: Glomerular capillary loop showing abundant small sub-epithelial electron-dense deposits. The overlying podocytes show extensive foot process effacement (electron microscopy, × 11,000). C: Large glomerular endothelial tubuloreticular inclusion is shown. Tiny sub-epithelial electron-dense deposits are also evident (electron microscopy, × 30,000).\n==== Refs\nReferences\n1 \nLu R \nZhao X \nLi J \nNiu P \nYang B \nWu H \nWang W \nSong H \nHuang B \nZhu N \nBi Y \nMa X \nZhan F \nWang L \nHu T \nZhou H \nHu Z \nZhou W \nZhao L \nChen J \nGenomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.\n\nLancet .\n2020 ;\n395 :\n565 –574\n.\n32007145 \n2 \nWang D \nHu B \nHu C \nZhu F \nLiu X \nZhang J \nWang B \nXiang H \nCheng Z \nXiong Y \nZhao Y \nLi Y \nWang X \nPeng Z \nClinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.\n\nJAMA .\n2020 ;\n323 :\n1061 –1069\n.\n32031570 \n3 \nZhang H \nPenninger JM \nLi Y \nZhong N \nSlutsky AS \nAngiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target.\n\nIntensive Care Med .\n2020 ;\n46 :\n586 –590\n.\n32125455 \n4 \nHamming I \nTimens W \nBulthuis ML \nLely AT \nNavis G \nvan Goor H \nTissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.\n\nJ Pathol .\n2004 ;\n203 :\n631 –637\n.\n15141377 \n5 \nCheng Y \nLuo R \nWang K \nZhang M \nWang Z \nDong L \nLi J \nYao Y \nGe S \nXu G \nKidney disease is associated with in-hospital death of patients with COVID-19.\n\nKidney Int .\n2020 ;\n97 :\n829 –838\n.\n32247631 \n6 \nYang X \nYu Y \nXu J \nClinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.\n\nLancet Respir Med .\n2020 ;\n8 :\n475 –481\n.\n32105632 \n7 \nArentz M \nYim E \nKlaff L \nLokhandwala S \nRiedo FX \nChong M \nLee M \nCharacteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State.\n\nJAMA .\n2020 ;\n323 :\n1612 –1614\n.\n32191259 \n8 \nGuan WJ \nNi ZY \nHu Y \nClinical characteristics of coronavirus disease 2019 in China [Epub ahead of print March 28.\n\nN Engl J Med .\n2020 ;\n382 :\n1708 –1720\n.\n32109013 \n9 \nZhou F \nYu T \nDu R \nFan G \nLiu Y \nLiu Z \nXiang J \nWang Y \nSong B \nGu X \nGuan L \nWei Y \nLi H \nWu X \nXu J \nTu S \nZhang Y \nChen H \nCao B \nClinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.\n\nLancet .\n2020 ;\n395 :\n1054 –1062\n.\n32171076 \n10 \nSu H \nYang M \nWan C \nYi LX \nTang F \nZhu HY \nYi F \nYang HC \nFogo AB \nNie X \nZhang C \nRenal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China.\n\nKidney Int .\n2020 ;\n98 :\n219 –227\n.\n32327202 \n11 \nLarsen CP \nBourne TD \nWilson JD \nSaqqa O \nSharshir MA \nCollapsing glomerulopathy in a patient With COVID-19.\n\nKidney Int Rep .\n2020 ;\n5 :\n935 –939\n.\n32292867 \n12 \nGaillard F \nIsmael S \nSannier A \nTarhini H \nVolpe T \nGreze C \nVerpont MC \nZouhry I \nRioux C \nLescure FX \nBuob D \nDaugas E \nTubuloreticular inclusions in COVID-19-related collapsing glomerulopathy.\n\nKidney Int .\n2020 ;\n98 : 241 .\n32471641 \n13 \nKissling S \nRotman S \nGerber C \nHalfon M \nLamoth F \nComte D \nLhopitallier L \nSadallah S \nFakhouri F \nCollapsing glomerulopathy in a COVID-19 patient.\n\nKidney Int .\n2020 ;\n98 :\n228 –231\n.\n32471639 \n14 \nPeleg Y \nKudose S \nD’Agati V \nSiddall E \nAhmad S \nKisselev S \nGharavi A \nCanetta P \nAcute kidney injury due to collapsing glomerulopathy following COVID-19 infection.\n\nKidney Int Rep .\n2020 ;\n5 :\n940 –945\n.\n32346659 \n15 \nSharma P \nUppal NN \nWanchoo R \nShah HH \nYang Y \nParikh R \nKhanin Y \nMadireddy V \nLarsen CP \nJhaveri KD \nBijol V \nCOVID-19-associated kidney injury: A case series of kidney biopsy findings.\n\nJ Am Soc Nephrol .\n2020 ;\n31 :\n1948 –1958\n.\n32660970 \n16 \nKudose S \nBatal I \nSantoriello D \nXu K \nBarasch J \nPeleg Y \nCanetta P \nRatner LE \nMarasa M \nGharavi AG \nStokes MB \nMarkowitz GS \nD’Agati VD \nKidney biopsy findings in patients with COVID-19.\n\nJ Am Soc Nephrol .\n2020 ;\n31 :\n1959 –1968\n.\n32680910 \n17 \nDiao B \nWang C \nWang R \nHuman kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Infection.\n\n2020 ;\ndoi: 10.1101/2020.03.04.20031120.\n\n18 \nBomback AS \nFervenza FC \nMembranous nephropathy: Approaches to treatment.\n\nAm J Nephrol .\n2018 ;\n47 :\n30 –42\n.\n\n19 \nWu A \nPeng Y \nHuang B \nDing X \nWang X \nNiu P \nMeng J \nZhu Z \nZhang Z \nWang J \nSheng J \nQuan L \nXia Z \nTan W \nCheng G \nJiang T \nGenome composition and divergence of the novel coronavirus (2019-nCoV) originating in China.\n\nCell Host Microbe .\n2020 ;\n27 :\n325 –328\n.\n32035028 \n20 \nRansick A \nLindström NO \nLiu J \nZhu Q \nGuo JJ \nAlvarado GF \nKim AD \nBlack HG \nKim J \nMcMahon AP \nSingle-cell profiling reveals sex, lineage, and regional diversity in the mouse kidney.\n\nDev Cell .\n2019 ;\n51 :\n399 –413.e7\n.\n31689386 \n21 \nHoffmann M \nKleine-Weber H \nSchroeder S \nKrüger N \nHerrler T \nErichsen S \nSchiergens TS \nHerrler G \nWu NH \nNitsche A \nMüller MA \nDrosten C \nPöhlmann S \nSARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor.\n\nCell .\n2020 ;\n181 :\n271 –280.e8\n.\n32142651 \n22 \nJefferson JA \nPippin JW \nShankland SJ \nExperimental models of membranous nephropathy.\n\nDrug Discov Today Dis Models .\n2010 ;\n7 :\n27 –33\n.\n21359154\n\n", "fulltext_license": "CC BY", "issn_linking": "2196-5293", "issue": "9()", "journal": "Clinical nephrology. Case studies", "keywords": "SRAS-CoV-2; acute kidney injury (AKI); coronavirus disease 2019 (COVID-19); membranous nephropathy (MN); renal pathology", "medline_ta": "Clin Nephrol Case Stud", "mesh_terms": null, "nlm_unique_id": "101638685", "other_id": null, "pages": "11-18", "pmc": null, "pmid": "33633925", "pubdate": "2021", "publication_types": "D002363:Case Reports", "references": "32660970;32007145;32346659;32031570;32109013;32171076;32191259;32471641;32680910;32125455;32247631;15141377;32327202;32471639;32035028;32292867;31689386;21359154;32142651;29852477;32105632", "title": "Membranous nephropathy in a patient with coronavirus disease 2019 (COVID-19): A case report.", "title_normalized": "membranous nephropathy in a patient with coronavirus disease 2019 covid 19 a case report" }

[ { "companynumb": "US-TEVA-2021-US-1927405", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "OLMESARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "091079", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OLMESARTAN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "074978", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400?800MG/DAY FOR YEARS", "drugenddate": null, "drugenddateformat": null, "drugindication": "NECK PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "HYDROCHLOROTHIAZIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "83177", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCHLOROTHIAZIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "METHYLPREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "085600", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPREDNISOLONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "LENZILUMAB" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "RECEIVED THREE DOSES IN TOTAL", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "600", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LENZILUMAB." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "HEPARIN SODIUM" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "FIBRIN D DIMER INCREASED", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HEPARIN" } ], "patientagegroup": "6", "patientonsetage": "81", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Intentional product misuse", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Renal tubular injury", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Hypoalbuminaemia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MIAO J, FIDLER ME, NASR SH, LARSEN CP, ZOGHBY ZM. MEMBRANOUS NEPHROPATHY IN A PATIENT WITH CORONAVIRUS DISEASE 2019 (COVID?19): A CASE REPORT. CLIN?NEPHROL?CASE?STUD 2021?9(1):11?18.", "literaturereference_normalized": "membranous nephropathy in a patient with coronavirus disease 2019 covid 19 a case report", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210806", "receivedate": "20210701", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19483859, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" }, { "companynumb": "US-HIKMA PHARMACEUTICALS USA INC.-US-H14001-21-02462", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "OLMESARTAN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OLMESARTAN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "HYDROCHLOROTHIAZIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "084878", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCHLOROTHIAZIDE." } ], "patientagegroup": null, "patientonsetage": "81", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Glomerulonephritis membranous", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MIAO J, FIDLER M, NASR S, LARSEN C, ZOGHBY Z. MEMBRANOUS NEPHROPATHY IN A PATIENT WITH CORONAVIRUS DISEASE 2019 (COVID?19): A CASE REPORT. CLINICAL NEPHROLOGY ? CASE STUDIES. 2021?9:11?18. DOI:10.5414/CNCS110379", "literaturereference_normalized": "membranous nephropathy in a patient with coronavirus disease 2019 covid 19 a case report", "qualification": null, "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20210528", "receivedate": "20210528", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19326783, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210717" }, { "companynumb": "US-GLAXOSMITHKLINE-USCH2021GSK028980", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "018989", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK (400?800 MG PER DAY)", "drugenddate": null, "drugenddateformat": null, "drugindication": "NECK PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "HYDROCHLOROTHIAZIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12.5 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPERTENSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCHLOROTHIAZIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OLMESARTAN" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "HYPERTENSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OLMESARTAN" } ], "patientagegroup": null, "patientonsetage": "81", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Renal tubular injury", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Proteinuria", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Acute kidney injury", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "MIAO J, FIDLER ME, NASR SH, LARSEN CP, ZOGHBY ZM. MEMBRANOUS NEPHROPATHY IN A PATIENT WITH CORONAVIRUS DISEASE 2019 (COVID?19): A CASE REPORT. CLINICAL NEPHROLOGY ? CASE STUDIES. 2021?9 (1):11?18", "literaturereference_normalized": "membranous nephropathy in a patient with coronavirus disease 2019 covid 19 a case report", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210519", "receivedate": "20210519", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19275153, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210717" }, { "companynumb": "US-STRIDES ARCOLAB LIMITED-2021SP006736", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "211666", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "400?800MG PER DAY FOR YEARS", "drugenddate": null, "drugenddateformat": null, "drugindication": "NECK PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OLMESARTAN MEDOXOMIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MILLIGRAM, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OLMESARTAN MEDOXOMIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "HYDROCHLOROTHIAZIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "12.5 MILLIGRAM DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "12.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCHLOROTHIAZIDE." } ], "patientagegroup": null, "patientonsetage": "81", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Renal tubular injury", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Intentional product misuse", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MIAO J, FIDLER ME, NASR SH, LARSEN CP, ZOGHBY ZM.. MEMBRANOUS NEPHROPATHY IN A PATIENT WITH CORONAVIRUS DISEASE 2019 (COVID?19): A CASE REPORT.. CLIN?NEPHROL?CASE?STUD. 2021?9(1):11?18", "literaturereference_normalized": "membranous nephropathy in a patient with coronavirus disease 2019 covid 19 a case report", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210913", "receivedate": "20210913", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19822973, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" } ]

{ "abstract": "BACKGROUND\nWe report the case of an adolescent with anticholinergic toxidrome from diphenhydramine overdose, whose symptoms were treated with a novel application of dexmedetomidine.\n\n\nMETHODS\nA 13-year-old female developed an anticholinergic toxidrome after intentionally ingesting 9.5 mg/kg of diphenhydramine. Despite routine supportive therapies, to include appropriate doses of lorazepam, she continued to have significant agitation, psychosis, and hallucinations. A dexmedetomidine infusion was started to aid in the treatment of her agitation and psychosis with marked improvement of her symptoms.\n\n\nCONCLUSIONS\nUsing dexmedetomidine for the treatment of anticholinergic toxidrome has not been previously described in the literature, but there are multiple reports of its use in alcohol withdrawal syndrome. We suggest that adding dexmedetomidine as an adjunctive agent in the therapy of anticholinergic toxidrome may relieve the symptoms of agitation, psychosis, tachycardia, and hypertension, without the attendant risk of respiratory depression associated with high doses of benzodiazepines.", "affiliations": "Department of Pediatrics, Naval Medical Center Portsmouth, 620 John Paul Jones Circle, Portsmouth, VA, 23708, USA.", "authors": "Walker|Ashley|A|;Delle Donne|Andrew|A|;Douglas|Elizabeth|E|;Spicer|Kristine|K|;Pluim|Thomas|T|", "chemical_list": "D018680:Cholinergic Antagonists; D020927:Dexmedetomidine; D004155:Diphenhydramine", "country": "United States", "delete": false, "doi": "10.1007/s13181-014-0408-1", "fulltext": null, "fulltext_license": null, "issn_linking": "1556-9039", "issue": "10(4)", "journal": "Journal of medical toxicology : official journal of the American College of Medical Toxicology", "keywords": null, "medline_ta": "J Med Toxicol", "mesh_terms": "D000293:Adolescent; D018680:Cholinergic Antagonists; D020927:Dexmedetomidine; D004155:Diphenhydramine; D062787:Drug Overdose; D005260:Female; D006801:Humans", "nlm_unique_id": "101284598", "other_id": null, "pages": "406-10", "pmc": null, "pmid": "24943229", "pubdate": "2014-12", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "22391930;12811715;20881501;1311158;15008410;10736125;16814639;24359283;21521867;12799407;16749537;22620986;20028214;3718632;3586086;18306834;18780809;3168512;23037682;12421743;21821507;17030289;23247391", "title": "Novel use of dexmedetomidine for the treatment of anticholinergic toxidrome.", "title_normalized": "novel use of dexmedetomidine for the treatment of anticholinergic toxidrome" }

[ { "companynumb": "US-BAYER-2014-100496", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "DIPHENHYDRAMINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "999999", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "24 PILLS OF DIPHENHYDRAMINE (25 MG EACH, TOTAL DOSE 600 MG, 9.5 MG/KG)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "24", "drugstructuredosageunit": "032", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIPHENHYDRAMINE HYDROCHLORIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "AMPHETAMINE ASPARTATE\\AMPHETAMINE SULFATE\\DEXTROAMPHETAMINE SACCHARATE\\DEXTROAMPHETAMINE SULFATE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "ATTENTION DEFICIT/HYPERACTIVITY DISORDER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ADDERALL XR" } ], "patientagegroup": "4", "patientonsetage": "13", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Anticholinergic syndrome", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Intentional overdose", "reactionmeddraversionpt": "17.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WALKER A, DELLE DONNE A, DOUGLAS E, SPICER K, PLUIM T. NOVEL USE OF DEXMEDETOMIDINE FOR THE TREATMENT OF ANTICHOLINERGIC TOXIDROME. J MED TOXICOL. 2014;ONLINE:ONLINE", "literaturereference_normalized": "novel use of dexmedetomidine for the treatment of anticholinergic toxidrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20140711", "receivedate": "20140711", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10297718, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150326" }, { "companynumb": "PHHY2014US170443", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DIPHENHYDRAMINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "080832", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "24 DF, (TOTAL DOSE 600 MG; 9.5 MG/KG)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "24", "drugstructuredosageunit": "032", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIPHENHYDRAMINE" } ], "patientagegroup": null, "patientonsetage": "13", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Mucosal dryness", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Mental status changes", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Anticholinergic syndrome", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Intentional overdose", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Flushing", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tachycardia", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Agitation", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hallucination, visual", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Aggression", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Confusional state", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Incoherent", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Mydriasis", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Psychotic disorder", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WALKER A, DELLE DONNE A, DOUGLAS E, SPICER K, PLUIM T.. NOVEL USE OF DEXMEDETOMIDINE FOR THE TREATMENT OF ANTICHOLINERGIC TOXIDROME.. J-MED-TOXICOL. 2014;10(4):406-10", "literaturereference_normalized": "novel use of dexmedetomidine for the treatment of anticholinergic toxidrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20150106", "receivedate": "20150106", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10693676, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150721" }, { "companynumb": "US-BANPHARM-20154325", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "DIPHENHYDRAMINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "090397", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DF 600MG, ONCE", "drugenddate": null, "drugenddateformat": null, "drugindication": "DRUG ABUSE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIPHENHYDRAMINE UNKNOWN PRODUCT" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "AMPHETAMINE ASPARTATE\\AMPHETAMINE SULFATE\\DEXTROAMPHETAMINE SACCHARATE\\DEXTROAMPHETAMINE SULFATE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DF 20MG, QD,", "drugenddate": null, "drugenddateformat": null, "drugindication": "ATTENTION DEFICIT/HYPERACTIVITY DISORDER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ADDERALL XR" } ], "patientagegroup": "4", "patientonsetage": "13", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Anticholinergic syndrome", "reactionmeddraversionpt": "18.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WALKER ASHLEY, ET AL. NOVEL USE OF DEXMEDETOMIDINE FOR THE TREATMENT OF ANTICHOLINERGIC TOXIDROME. J. MED. TOXICOL. 2014? 10:406-410 DOI 10.1007/S13181-014-0408-1.", "literaturereference_normalized": "novel use of dexmedetomidine for the treatment of anticholinergic toxidrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20151023", "receivedate": "20151023", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11656086, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160304" }, { "companynumb": "US-JNJFOC-20141207782", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "DIPHENHYDRAMINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNSPECIFIED", "drugdosagetext": "APPROXIMATELY 24 PILLS OF 25MG EACH , TOTAL 600MG, 9.5 MG/KG", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DIPHENHYDRAMINE HYDROCHLORIDE." } ], "patientagegroup": "4", "patientonsetage": "13", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Anticholinergic syndrome", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Intentional overdose", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "WALKER A, DONNE AD, DOUGLAS E, SPICER K, PLUIM T. NOVEL USE OF DEXMEDETOMIDINE FOR THE TREATMENT OF ANTICHOLINERGIC TOXIDROME. J MED TOXICOL 2014;10:406-10.", "literaturereference_normalized": "novel use of dexmedetomidine for the treatment of anticholinergic toxidrome", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20141219", "receivedate": "20141219", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10663449, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20150529" } ]

{ "abstract": "Naloxegol is a new peripherally acting mu-opioid receptor antagonist to treat opioid-induced constipation with supposedly no effect on opioid analgesia. We present a patient with cancer-related pain who developed acute opioid withdrawal symptoms due to an interaction between the opioid antagonist naloxone and naloxegol. He was treated with oxycodone sustained release because of poor pain control. For opioid-related constipation, he had been receiving naloxegol. He complained about worsening pain and constipation and oxycodone was switched to oxycodone/naloxone. Shortly after intake, he experienced acute severe agitation, anxiety, sweating, tachycardia, disorientation and yawning without improvement after intravenous midazolam. Only after intravenous morphine administration, symptoms were controlled. He was switched back to the previous oxycodone dose without naloxone, with naloxegol being maintained. In the light of this case we suggest to avoid the use of naloxone and naloxegol in combination, or at least, to use it with extreme caution and monitorisation of tolerance.", "affiliations": "Palliative Care Unit, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain molmo@iconcologia.net.;Palliative Care Unit, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.;Palliative Care Unit, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.;Oncologic Emergency Room, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spaing.;Palliative Care Unit, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.", "authors": "Olmo|Montserrat|M|http://orcid.org/0000-0002-0004-5829;González-Barboteo|Jesús|J|;Moreno|Deborah|D|;Coma|Eva|E|;Serrano|Gala|G|", "chemical_list": "D000701:Analgesics, Opioid; D009019:Morphinans; D009292:Narcotic Antagonists; D009270:Naloxone; D011092:Polyethylene Glycols; C000589308:naloxegol; D010098:Oxycodone", "country": "England", "delete": false, "doi": "10.1136/bmjspcare-2020-002387", "fulltext": null, "fulltext_license": null, "issn_linking": "2045-435X", "issue": "11(4)", "journal": "BMJ supportive & palliative care", "keywords": "constipation; drug administration; pain; pharmacology", "medline_ta": "BMJ Support Palliat Care", "mesh_terms": "D000701:Analgesics, Opioid; D003248:Constipation; D006801:Humans; D008297:Male; D009019:Morphinans; D009270:Naloxone; D009292:Narcotic Antagonists; D010098:Oxycodone; D011092:Polyethylene Glycols; D013375:Substance Withdrawal Syndrome", "nlm_unique_id": "101565123", "other_id": null, "pages": "408-410", "pmc": null, "pmid": "32788278", "pubdate": "2021-12", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Acute opioid withdrawal syndrome from naloxone/naloxegol interaction.", "title_normalized": "acute opioid withdrawal syndrome from naloxone naloxegol interaction" }

[ { "companynumb": "ES-VIRTUS PHARMACEUTICALS, LLC-2020VTS00063", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "NALOXONE HYDROCHLORIDE\\OXYCODONE HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "207846", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "60/30 MG (40/20 MG PLUS 20/10 MG), 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC NEUROENDOCRINE TUMOUR METASTATIC", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXONE?OXYCODONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "OXYCODONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MG, 2X/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXYCODONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "FENTANYL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FENTANYL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "OMEPRAZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMEPRAZOLE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "UNSPECIFIED INSULIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "NALOXONE HYDROCHLORIDE\\OXYCODONE HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "207846", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CONSTIPATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXONE?OXYCODONE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "NALOXEGOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CONSTIPATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXEGOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ACETAMINOPHEN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACETAMINOPHEN." } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug withdrawal syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "OLMO M, GONZALEZ?BARBOTEO J, MORENDO D., ET AL.. ACUTE OPIOID WITHDRAWAL SYNDROME FROM NALOXONE/NALOXEGOL INTERACTION. BMJ SUPPORT PALLIAT.CARE. 2020", "literaturereference_normalized": "acute opioid withdrawal syndrome from naloxone naloxegol interaction", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20200908", "receivedate": "20200908", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18241788, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" }, { "companynumb": "ES-BIODELIVERY SCIENCES INTERNATIONAL-2020BDSI0563", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "ACETAMINOPHEN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PARACETAMOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "OMEPRAZOLE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMEPRAZOLE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NALOXONE HYDROCHLORIDE\\OXYCODONE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "TOTAL 60/30 MG TWICE DAILY (DIVIDED IN 40/20 MG PILL AND 20/10 MG PILL)", "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXYCODONE/NALOXONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NALOXEGOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CONSTIPATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXEGOL" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "STREPTOZOCIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "STREPTOZOCIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NALOXONE HYDROCHLORIDE\\OXYCODONE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "TOTAL 60/30 MG TWICE DAILY (DIVIDED IN 40/20 MG PILL AND 20/10 MG PILL)", "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXYCODONE/NALOXONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DOXORUBICIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXORUBICIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "EVEROLIMUS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EVEROLIMUS." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "SUNITINIB" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SUNITINIB" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "OXYCODONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXYCODONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "FENTANYL CITRATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "022266", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FENTANYL CITRATE." } ], "patientagegroup": "5", "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug withdrawal syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Constipation", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MONTSERRAT O, GONZALEZ?BARBOTEO J, MORENO D, COMA E, SERRANO G. ACUTE OPIOID WITHDRAWAL SYNDROME FROM NALOXONE/NALOXEGOL INTERACTION. BMJ?SUPPORT?PALLIAT?CARE. 2020?.", "literaturereference_normalized": "acute opioid withdrawal syndrome from naloxone naloxegol interaction", "qualification": "1", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20200910", "receivedate": "20200910", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 18251999, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" }, { "companynumb": "ES-SUN PHARMACEUTICAL INDUSTRIES LTD-2020R1-260328", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "NALOXEGOL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXOGEL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXYCODONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "90659", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXYCODONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "NALOXONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXONE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Drug withdrawal syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Condition aggravated", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "OLMO M, GONZALEZ?BARBOTEO J, MORENO D, COMA E, SERRANO G. ACUTE OPIOID WITHDRAWAL SYNDROME FROM NALOXONE/NALOXEGOL INTERACTION. BMJ SUPPORT PALLIAT CARE. 2020?NO PAGINATION", "literaturereference_normalized": "acute opioid withdrawal syndrome from naloxone naloxegol interaction", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20200915", "receivedate": "20200915", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18269132, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "ES-TEVA-2020-ES-1829544", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "SUNITINIB" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC NEUROENDOCRINE TUMOUR METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SUNITINIB" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OMEPRAZOLE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMEPRAZOLE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EVEROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC NEUROENDOCRINE TUMOUR METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EVEROLIMUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FENTANYL" }, "drugadditional": "3", "drugadministrationroute": "050", "drugauthorizationnumb": "020747", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FENTANYL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "STREPTOZOCIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC NEUROENDOCRINE TUMOUR METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "STREPTOZOCIN" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "NALOXONE HYDROCHLORIDE\\OXYCODONE HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "TOTAL 60/30 MG TWICE DAILY: (DIVIDED IN 40/20 MG PILL AND 20/10 MG PILL)", "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXONE W/ OXYCODONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DOXORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC NEUROENDOCRINE TUMOUR METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXORUBICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ACETAMINOPHEN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACETAMINOPHEN." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "NALOXEGOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CONSTIPATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXEGOL" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "OXYCODONE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "80 MILLIGRAM DAILY;", "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXYCODONE" } ], "patientagegroup": "5", "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Constipation", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug withdrawal syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "OLMO M, GONZALEZ?BARBOTEO J, MORENO D, COMA E, SERRANO G. ACUTE OPIOID WITHDRAWAL SYNDROME FROM NALOXONE/NALOXEGOL INTERACTION. BMJ?SUPPORT?PALLIAT?CARE 2020?:.", "literaturereference_normalized": "acute opioid withdrawal syndrome from naloxone naloxegol interaction", "qualification": "1", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20200922", "receivedate": "20200922", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18292182, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" }, { "companynumb": "ES-ALKEM LABORATORIES LIMITED-ES-ALKEM-2020-06185", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "ACETAMINOPHEN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACETAMINOPHEN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "OMEPRAZOLE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMEPRAZOLE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "FENTANYL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FENTANYL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "OXYCODONE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "211749", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANALGESIC THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXYCODONE HYDROCHLORIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pain", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Constipation", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "OLMO M, GONZALEZ-BARBOTEO J, MORENO D, COMA E, ET.AL. ACUTE OPIOID WITHDRAWAL SYNDROME FROM NALOXONE/NALOXEGOL INTERACTION. BMJ SUPPORTIVE + PALLIATIVE CARE. 2020?0:1-3", "literaturereference_normalized": "acute opioid withdrawal syndrome from naloxone naloxegol interaction", "qualification": "3", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20201130", "receivedate": "20201130", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18558165, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 2, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210114" }, { "companynumb": "ES-MYLANLABS-2020M1077985", "fulfillexpeditecriteria": "1", "occurcountry": "ES", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "NALOXEGOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CONSTIPATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXEGOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOCLOPRAMIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOCLOPRAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ACETAMINOPHEN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACETAMINOPHEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EVEROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC NEUROENDOCRINE TUMOUR METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EVEROLIMUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OMEPRAZOLE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMEPRAZOLE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "NALOXONE HYDROCHLORIDE\\OXYCODONE HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "TOTAL 60/30 MG TWICE DAILY: (DIVIDED IN 40/20 MG PILL AND 20/10 MG PILL)", "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXONE/OXYCODONE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "NALOXONE HYDROCHLORIDE\\OXYCODONE HYDROCHLORIDE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "3", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "TOTAL 60/30 MG TWICE DAILY: (DIVIDED IN 40/20 MG PILL AND 20/10 MG PILL))", "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "NALOXONE/OXYCODONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "FENTANYL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "076258", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FENTANYL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SUNITINIB" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC NEUROENDOCRINE TUMOUR METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SUNITINIB" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "OXYCODONE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MILLIGRAM, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "CANCER PAIN", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXYCODONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "STREPTOZOCIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC NEUROENDOCRINE TUMOUR METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "STREPTOZOCIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DOXORUBICIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PANCREATIC NEUROENDOCRINE TUMOUR METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DOXORUBICIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug withdrawal syndrome", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Constipation", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Drug interaction", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "OLMO M, GONZALEZ?BARBOTEO J, MORENO D, COMA E, SERRANO G. ACUTE OPIOID WITHDRAWAL SYNDROME FROM NALOXONE/NALOXEGOL INTERACTION. BMJ?SUPPORT?PALLIAT?CARE 2020?NULL:NULL.", "literaturereference_normalized": "acute opioid withdrawal syndrome from naloxone naloxegol interaction", "qualification": "1", "reportercountry": "ES" }, "primarysourcecountry": "ES", "receiptdate": "20200911", "receivedate": "20200911", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18257753, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20201103" } ]

{ "abstract": "BACKGROUND\nWe report the case of a patient who experienced severe neurological symptoms collectively characterized as being \"frozen\" following a second oxaliplatin infusion.\n\n\nMETHODS\nA 52-year-old woman with metastatic colon cancer developed severe motor slowing, delayed and incomplete grip and dorsiflexion, speech difficulty, visual impairment, leg cramping and tingling after her second infusion of oxaliplatin. She was transferred from the infusion center to the emergency room and admitted to the hospital for further evaluation. Motor, verbal, and ocular symptoms gradually resolved within 24 hours, and she was discharged home without sequela.Management and outcome: Oxaliplatin dose was subsequently lowered and infusion time increased, and she tolerated future treatments without motor, verbal, or ocular disturbance.\n\n\nCONCLUSIONS\nIn this case report, we describe a rare form of neurological toxicity involving severe motor slowing, slurred speech, and blurry vision secondary to oxaliplatin.", "affiliations": "Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Rogel Cancer Center, Ann Arbor, USA.;Department of Pharmacy, University of Michigan Rogel Cancer Center, Ann Arbor, USA.;Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, USA.;Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Rogel Cancer Center, Ann Arbor, USA.", "authors": "Patel|Monica A|MA|;McDevitt|Rachel L|RL|https://orcid.org/0000-0001-7209-8818;Sassack|Will|W|;Zalupski|Mark M|MM|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1177/10781552211004985", "fulltext": null, "fulltext_license": null, "issn_linking": "1078-1552", "issue": null, "journal": "Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners", "keywords": "Oxaliplatin; eloxatin; oxalatin; toxicity", "medline_ta": "J Oncol Pharm Pract", "mesh_terms": null, "nlm_unique_id": "9511372", "other_id": null, "pages": "10781552211004985", "pmc": null, "pmid": "33765873", "pubdate": "2021-03-26", "publication_types": "D016428:Journal Article", "references": null, "title": "Motor \"freezing\" with oxaliplatin.", "title_normalized": "motor freezing with oxaliplatin" }

[ { "companynumb": "US-QILU PHARMACEUTICAL CO.LTD.-QLU-000065-2021", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "204368", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "130 MILLIGRAM/SQ. METER, FOR 2 HOURS", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLON CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "130", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CAPECITABINE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG/M2, BID (ON DAYS 1?14)", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLON CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CAPECITABINE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "204368", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "85 MILLIGRAM/SQ. METER, EVERY 14 DAYS, FOR 4 HOURS", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "85", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Tremor", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypokinesia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Grip strength decreased", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cold dysaesthesia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Speech disorder developmental", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Muscle tightness", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Vision blurred", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Paraesthesia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Blepharospasm", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Dysarthria", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypertonia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Dysphonia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Visual field defect", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PATEL MA MCDEVITT RL SASSACK W ZALUPSKI MM. MOTOR ^FREEZING^ WITH OXALIPLATIN. JOURNAL OF ONCOLOGY PHARMACY PRACTICE. 2021?1?4", "literaturereference_normalized": "motor freezing with oxaliplatin", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210917", "receivedate": "20210917", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19847707, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" }, { "companynumb": "US-MLMSERVICE-20210405-2820038-1", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "1", "drugadministrationroute": "041", "drugauthorizationnumb": "078813", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": "130", "drugcumulativedosageunit": "009", "drugdosageform": "Solution for injection", "drugdosagetext": "130 MG/M2, ON DAY 1, EVERY 21 DAYS", "drugenddate": "20200212", "drugenddateformat": "102", "drugindication": "Colon cancer metastatic", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "20190925", "drugstartdateformat": "102", "drugstructuredosagenumb": "130", "drugstructuredosageunit": "009", "drugtreatmentduration": "141", "drugtreatmentdurationunit": "804", "medicinalproduct": "OXALIPLATIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CAPECITABINE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG/M2, ON DAYS 1-14, EVERY 21 DAYS (TWICE DAILY )", "drugenddate": null, "drugenddateformat": null, "drugindication": "Colon cancer metastatic", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2019", "drugstartdateformat": "602", "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CAPECITABINE" } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": "98", "reaction": [ { "reactionmeddrapt": "Cold dysaesthesia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Grip strength decreased", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Temperature intolerance", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tremor", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Dysarthria", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypertonia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Paraesthesia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypokinesia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hyporeflexia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Vision blurred", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Neurotoxicity", "reactionmeddraversionpt": "24.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20190101" } }, "primarysource": { "literaturereference": "McDevitt, R.. Motor ^freezing^ with oxaliplatin.. Journal of Oncology Pharmacy Practice. 2021;10.1177/10781552211004985", "literaturereference_normalized": "motor freezing with oxaliplatin", "qualification": "2", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20220308", "receivedate": "20210419", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19153088, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" }, { "companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2021R1-290931", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "202922", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "INFUSION", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLON CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Nervous system disorder", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PATEL MA, MCDEVITT RL, SASSACK W,. MOTOR ^FREEZING^ WITH OXALIPLATIN. J ONCOL PHARM PRACT. 2021?MAR 26? 1078155:ONLINE AHEAD OF PRINT", "literaturereference_normalized": "motor freezing with oxaliplatin", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210414", "receivedate": "20210414", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19130209, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210717" }, { "companynumb": "US-FRESENIUS KABI-FK202104075", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "CAPECITABINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "SECOND CYCLE OF CAPOX WITHOUT DOSE REDUCTION", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CAPECITABINE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "078811", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "IV; 130 MG/M2 ON DAY 1; EVERY 21 DAYS (CAPOX)", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLON CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "130", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN (MANUFACTURER UNKNOWN)" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "078811", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "SECOND CYCLE OF CAPOX WITHOUT DOSE REDUCTION", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN (MANUFACTURER UNKNOWN)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CAPECITABINE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": "1000 MG/M2, TWICE DAILY ON DAYS 1?14; EVERY 21 DAYS (CAPOX)", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLON CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CAPECITABINE." } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Cold dysaesthesia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Neurotoxicity", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Freezing phenomenon", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PATEL M, MCDEVITT R, MCDEVITT R, SASSACK W, ZALUPSKI M. MOTOR FREEZING WITH OXALIPLATIN. JOURNAL OF ONCOLOGY PHARMACY PRACTICE. 2021 MAR 26?0 (0):1?4.", "literaturereference_normalized": "motor freezing with oxaliplatin", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210422", "receivedate": "20210422", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19169810, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210717" }, { "companynumb": "US-PFIZER INC-2021442242", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "078813", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "85 MG/M2, CYCLIC (EVERY 14 DAYS)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "85", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "078813", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "130 MG/M2, EVERY 3 WEEKS (ON DAY 1, EVERY 21 DAYS)", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLON CANCER METASTATIC", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "130", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CAPECITABINE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1000 MG/M2, TWICE DAILY ON DAYS 1?14, EVERY 21 DAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLON CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CAPECITABINE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "078813", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INJECTION", "drugdosagetext": "130 MG/M2, EVERY 3 WEEKS (ON DAY 1, EVERY 21 DAYS)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "130", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." } ], "patientagegroup": null, "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Bradykinesia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Bradyphrenia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Speech disorder", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Dysarthria", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Vision blurred", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Tremor", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Paraesthesia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Hypertonia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cold dysaesthesia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "PATEL, M.. MOTOR ^^FREEZING^^ WITH OXALIPLATIN. JOURNAL OF ONCOLOGY PHARMACY PRACTICE. 2021?0 (0):10.1177/10781552211004985", "literaturereference_normalized": "motor freezing with oxaliplatin", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210422", "receivedate": "20210422", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19168975, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210717" }, { "companynumb": "US-TEVA-2021-US-1904690", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CAPECITABINE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "CAPOX REGIMEN; ON DAYS 1?14, EVERY 21 DAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLON CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CAPECITABINE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "1", "drugadministrationroute": "041", "drugauthorizationnumb": "022160", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "CAPOX REGIMEN; ON DAY 1, EVERY 21 DAYS", "drugenddate": null, "drugenddateformat": null, "drugindication": "COLON CANCER METASTATIC", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "2", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "130", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." } ], "patientagegroup": "5", "patientonsetage": "52", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Freezing phenomenon", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Neurotoxicity", "reactionmeddraversionpt": "24.0", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "PATEL MA, MCDEVITT RL, SASSACK W, ZALUPSKI MM. MOTOR ^FREEZING^ WITH OXALIPLATIN. J?ONCOL?PHARM?PRACT 2021?:1?4.", "literaturereference_normalized": "motor freezing with oxaliplatin", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210628", "receivedate": "20210429", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19196625, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210717" } ]

{ "abstract": "In a 59-year old man with IIIb non-small-cell lung cancer, a combined treatment with paclitaxel and carboplatin was used for potentiation of radiotherapy. The patient was alive and free of neoplastic disease 14 months after the end of treatment but irreversible lung fibrosis had developed.", "affiliations": "Service de Médecine Interne, Institut Jules Bordet, Université Libre de Bruxelles, Belgium.", "authors": "Sotiriou|C|C|;van Houtte|P|P|;Klastersky|J|J|", "chemical_list": "D011838:Radiation-Sensitizing Agents; D016190:Carboplatin; D017239:Paclitaxel", "country": "Germany", "delete": false, "doi": "10.1007/s005200050135", "fulltext": null, "fulltext_license": null, "issn_linking": "0941-4355", "issue": "6(1)", "journal": "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer", "keywords": null, "medline_ta": "Support Care Cancer", "mesh_terms": "D000971:Antineoplastic Combined Chemotherapy Protocols; D016190:Carboplatin; D002289:Carcinoma, Non-Small-Cell Lung; D017024:Chemotherapy, Adjuvant; D006801:Humans; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel; D011658:Pulmonary Fibrosis; D011838:Radiation-Sensitizing Agents; D014057:Tomography, X-Ray Computed", "nlm_unique_id": "9302957", "other_id": null, "pages": "68-71", "pmc": null, "pmid": "9458540", "pubdate": "1998-01", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Lung fibrosis induced by paclitaxel.", "title_normalized": "lung fibrosis induced by paclitaxel" }

[ { "companynumb": "BE-PFIZER INC-2019330864", "fulfillexpeditecriteria": "1", "occurcountry": "BE", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "PROMETHAZINE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "030", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG, UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PREMEDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PROMETHAZINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "076131", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG/M2, CYCLIC (IN 1 HR)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "076131", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200 MG/M2, CYCLIC (IN 3 H)", "drugenddate": null, "drugenddateformat": null, "drugindication": "NON-SMALL CELL LUNG CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "20 MG, UNK ( 12H AND 6 H BEFORE TREATMENT)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PREMEDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "20", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "RANITIDINE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG, UNK (30 MIN BEFORE EACH TREATMENT.)", "drugenddate": null, "drugenddateformat": null, "drugindication": "PREMEDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RANITIDINE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": "1", "drugadministrationroute": "040", "drugauthorizationnumb": "076517", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG/M2, CYCLIC (ON THE 1ST AND 3RD DAYS OF EACH WEEK)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "076517", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "EVERY 3 WEEKS (TOTAL DOSE OF 650 MG I.V. IN 2 H EVERY 3 WEEKS)", "drugenddate": null, "drugenddateformat": null, "drugindication": "NON-SMALL CELL LUNG CANCER", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "3", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." } ], "patientagegroup": null, "patientonsetage": "59", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pulmonary fibrosis", "reactionmeddraversionpt": "22.0", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "SOTIRIOU, A.. LUNG FIBROSIS INDUCED BY PACLITAXEL. SUPPORTIVE CARE IN CANCER. 1997?6 (1):68-71", "literaturereference_normalized": "lung fibrosis induced by paclitaxel", "qualification": "1", "reportercountry": "BE" }, "primarysourcecountry": "BE", "receiptdate": "20190806", "receivedate": "20190806", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16672554, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20191004" } ]

{ "abstract": "Combining antiviral regimens in the hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfected population can be complex as they share overlapping mechanisms for elimination that may result in drug interactions. The pharmacokinetics, safety, and tolerability of sofosbuvir/velpatasvir (SOF/VEL) with multiple antiretroviral (ARV) regimens were evaluated.\n\n\n\nHealthy volunteers were enrolled into 2 phase 1, open-label, randomized, multiple-dose, cross-over studies. SOF/VEL and ARV regimens were administered alone and in combination; ARVs (and pharmacokinetic enhancers) included atazanavir (ATV), cobicistat (COBI), darunavir (DRV), dolutegravir (DTG), efavirenz (EFV), elvitegravir (EVG), emtricitabine (FTC), lopinavir (LPV), raltegravir (RAL), rilpivirine (RPV), ritonavir (RTV), tenofovir alafenamide (TAF), and tenofovir disoproxil fumarate (TDF). Geometric least squares means ratios (coadministration:alone) and 90% confidence intervals were constructed for area under the plasma concentration-time curve over the dosing interval, maximum concentration, and trough, for all analytes. Safety and tolerability were also evaluated.\n\n\n\nIn total, 237 participants were enrolled. No clinically relevant differences in the pharmacokinetics (PK) of SOF, SOF metabolite GS-331007, or VEL were observed other than an approximate 50% decrease in VEL exposure when administered with EFV/FTC/TDF. No clinically relevant differences in the PK of ARVs were observed when administered with SOF/VEL. Study treatments were well tolerated, including no observed creatinine clearance changes during evaluation of TDF-containing regimens.\n\n\n\nSOF/VEL and ARV regimens including ATV, COBI, DRV, DTG, EVG, FTC, LPV, RAL, RPV, RTV, TAF, or TDF may be coadministered without dose adjustment. Use of SOF/VEL with EFV-containing regimens is not recommended due to an approximate 50% reduction in VEL exposure.", "affiliations": "Gilead Sciences, Foster City, California.;Gilead Sciences, Foster City, California.;Gilead Sciences, Foster City, California.;Gilead Sciences, Foster City, California.;Gilead Sciences, Foster City, California.;Gilead Sciences, Foster City, California.;Gilead Sciences, Foster City, California.", "authors": "Mogalian|Erik|E|;Stamm|Luisa M|LM|;Osinusi|Anu|A|;Brainard|Diana M|DM|;Shen|Gong|G|;Ling|Kah Hiing John|KHJ|;Mathias|Anita|A|", "chemical_list": "D019380:Anti-HIV Agents; D002219:Carbamates; D006576:Heterocyclic Compounds, 4 or More Rings; D000068698:Tenofovir; C000604171:velpatasvir; D000069474:Sofosbuvir", "country": "United States", "delete": false, "doi": "10.1093/cid/ciy201", "fulltext": null, "fulltext_license": null, "issn_linking": "1058-4838", "issue": "67(6)", "journal": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America", "keywords": null, "medline_ta": "Clin Infect Dis", "mesh_terms": "D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents; D002219:Carbamates; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006576:Heterocyclic Compounds, 4 or More Rings; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069474:Sofosbuvir; D000068698:Tenofovir; D055815:Young Adult", "nlm_unique_id": "9203213", "other_id": null, "pages": "934-940", "pmc": null, "pmid": "29522076", "pubdate": "2018-08-31", "publication_types": "D017426:Clinical Trial, Phase I; D016428:Journal Article; D016449:Randomized Controlled Trial; D013485:Research Support, Non-U.S. Gov't", "references": null, "title": "Drug-Drug Interaction Studies Between Hepatitis C Virus Antivirals Sofosbuvir/Velpatasvir and Boosted and Unboosted Human Immunodeficiency Virus Antiretroviral Regimens in Healthy Volunteers.", "title_normalized": "drug drug interaction studies between hepatitis c virus antivirals sofosbuvir velpatasvir and boosted and unboosted human immunodeficiency virus antiretroviral regimens in healthy volunteers" }

[ { "companynumb": "US-GILEAD-2018-0370965", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "SOFOSBUVIR\\VELPATASVIR" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SOFOSBUVIR W/VELPATASVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DARUNAVIR" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DARUNAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EMTRICITABINE\\RILPIVIRINE\\TENOFOVIR DISOPROXIL FUMARATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "202123", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EMTRICITABINE/RILPIVIRINE/TENOFOVIR DF" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EMTRICITABINE\\TENOFOVIR DISOPROXIL FUMARATE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": "DOSAGE FORM: UNSPECIFIED", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EMTRICITABINE/TENOFOVIR DISOPROXIL FUMARATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RITONAVIR" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "DOSAGE FORM: UNSPECIFIED", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITONAVIR." } ], "patientagegroup": "5", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Blood urine present", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Constipation", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Headache", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MOGALIAN E, STAMM LM, OSINUSI A, BRAINARD DM, SHEN G, KAH HJ, ET AL.. DRUG-DRUG INTERACTION STUDIES BETWEEN HEPATITIS C VIRUS ANTIVIRALS SOFOSBUVIR/VELPATASVIR AND BOOSTED AND UNBOOSTED HUMAN IMMUNODEFICIENCY VIRUS ANTIRETROVIRAL REGIMENS IN HEALTHY VOLUNTEERS. CLINICAL INFECTIOUS DISEASES. 2018?67(6):934-940", "literaturereference_normalized": "drug drug interaction studies between hepatitis c virus antivirals sofosbuvir velpatasvir and boosted and unboosted human immunodeficiency virus antiretroviral regimens in healthy volunteers", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181025", "receivedate": "20181025", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15552221, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" }, { "companynumb": "US-JNJFOC-20181024858", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DARUNAVIR" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "021976", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLETS", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DARUNAVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EMTRICITABINE\\TENOFOVIR DISOPROXIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNSPECIFIED", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EMTRICITABINE W/TENOFOVIR DISOPROXIL FUMARATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "RITONAVIR" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNSPECIFIED", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RITONAVIR." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SOFOSBUVIR" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SOFOSBUVIR" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "EMTRICITABINE\\RILPIVIRINE\\TENOFOVIR DISOPROXIL FUMARATE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "000000", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "EMTRICITABINE/RILPIVIRINE/TENOFOVIR DISOPROXIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VELPATASVIR" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLET", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VELPATASVIR" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Headache", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Blood urine present", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Constipation", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MOGALIAN E, STAMM LM, OSINUSI A, BRAINARD DM, SHEN G, KAH HJ, ET AL. DRUG-DRUG INTERACTION STUDIES BETWEEN HEPATITIS C VIRUS ANTIVIRALS SOFOSBUVIR/VELPATASVIR AND BOOSTED AND UNBOOSTED HUMAN IMMUNODEFICIENCY VIRUS ANTIRETROVIRAL REGIMENS IN HEALTHY VOLUNTEERS. CLINICAL INFECTIOUS DISEASES 31-AUG-2018?67(6):934-940.", "literaturereference_normalized": "drug drug interaction studies between hepatitis c virus antivirals sofosbuvir velpatasvir and boosted and unboosted human immunodeficiency virus antiretroviral regimens in healthy volunteers", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20181025", "receivedate": "20181022", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15538273, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" } ]

{ "abstract": "To evaluate the effect of capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer.\n\n\n\nPatients with rectum cancer T4 or T3 involving the mesorectal fascia was included in a prospective phase 2 trial. Liver or lung metastases were accepted if the surgeons found them resectable. The patients received 6 weeks of capecitabine and oxaliplatin before chemoradiotherapy (CRT), continued capecitabine and oxaliplatin during radiotherapy, and received 4 weeks of capecitabine and oxaliplatin after CRT. The patients received radiotherapy as intensity-modulated radiotherapy. Total mesorectal excision was planned 8 weeks after CRT. The patients were evaluated with magnetic resonance imaging (MRI) before start of treatment, after 6 weeks of chemotherapy, and again just before the operation. The European Organization for Research and Treatment of Cancer (EORTC) QLQ-CR29 scoring system was used to evaluate adverse events.\n\n\n\nFifty-two patients were enrolled between 2009 and 2012. The treatment was well tolerated, with only one death during treatment. Eighty percent of assessable patients experienced response to chemotherapy alone as evaluated by MRI, which increased to 94% after complete oncologic treatment. Forty-nine patients had a total mesorectal excision performed, all with a R0 resection and with a pathologic complete response of 20% for patients with T3 tumor and 7% for patients with T4 tumor. Five patients had metastases at study entry, while 47 patients had locally advanced rectal cancer without metastases. Of these 47 patients, overall survival and progression-free survival at 5 years was 72% and 62%, respectively, with a median follow-up of 60 months.\n\n\n\nThis aggressive approach with capecitabine and oxaliplatin before, during, and after radiotherapy for high-risk rectal cancer is safe and feasible; it also has an impressive response rate as measured by MRI and a promising 5-year overall survival.", "affiliations": "Department of Oncology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark. Electronic address: Finn.Ole.Larsen@regionh.dk.;Department of Oncology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark.;Department of Oncology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark.;Department of Oncology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark.;Department of Oncology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark.;Department of Oncology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark.;Department of Pathology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark.;Department of Radiology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark.;Department of Radiology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark.;Department of Oncology, Copenhagen University Hospital, Herlev-Gentofte, Herlev, Denmark.", "authors": "Larsen|Finn Ole|FO|;Markussen|Alice|A|;Jensen|Benny V|BV|;Fromm|Anne L|AL|;Vistisen|Kirsten K|KK|;Parner|Vibeke K|VK|;Linnemann|Dorte|D|;Hansen|Rasmus H|RH|;Johannesen|Helle H|HH|;Schou|Jakob V|JV|", "chemical_list": "D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine", "country": "United States", "delete": false, "doi": "10.1016/j.clcc.2016.07.020", "fulltext": null, "fulltext_license": null, "issn_linking": "1533-0028", "issue": "16(2)", "journal": "Clinical colorectal cancer", "keywords": "IMRT; LARC; Neoadjuvant; Radiotherapy; Rectum cancer", "medline_ta": "Clin Colorectal Cancer", "mesh_terms": "D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D000069287:Capecitabine; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D011446:Prospective Studies; D050397:Radiotherapy, Intensity-Modulated; D012004:Rectal Neoplasms", "nlm_unique_id": "101120693", "other_id": null, "pages": "e7-e14", "pmc": null, "pmid": "27743742", "pubdate": "2017-06", "publication_types": "D017427:Clinical Trial, Phase II; D016428:Journal Article", "references": null, "title": "Capecitabine and Oxaliplatin Before, During, and After Radiotherapy for High-Risk Rectal Cancer.", "title_normalized": "capecitabine and oxaliplatin before during and after radiotherapy for high risk rectal cancer" }

[ { "companynumb": "DK-ROCHE-1872606", "fulfillexpeditecriteria": "1", "occurcountry": "DK", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CETUXIMAB" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RECTAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "500", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CETUXIMAB" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "OXALIPLATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RECTAL CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OXALIPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CAPECITABINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "020896", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RECTAL CANCER", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "650", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CAPECITABINE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Death", "reactionmeddraversionpt": "19.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Neurotoxicity", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fatigue", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Chronic obstructive pulmonary disease", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Palmar-plantar erythrodysaesthesia syndrome", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pneumonia", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "19.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LARSEN F, MARKUSSEN A, JENSEN B, FROMM A, VISTISEN K, PARNER V, LINNEMANN D, HANSEN R, JOHANNESEN H AND SCHOU J. CAPECITABINE AND OXALIPLATIN BEFORE, DURING, AND AFTER RADIOTHERAPY FOR HIGH-RISK RECTAL CANCER.. CLINICAL COLORECTAL CANCER 2016 FEB 29;:-.", "literaturereference_normalized": "capecitabine and oxaliplatin before during and after radiotherapy for high risk rectal cancer", "qualification": "1", "reportercountry": "DK" }, "primarysourcecountry": "DK", "receiptdate": "20161230", "receivedate": "20161230", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 13074485, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20170207" } ]

{ "abstract": "Information about the use of ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin (OBV/PTV/r/DSV ± RBV) in real-clinical practice in Latin America is scarce. We aimed to confirm safety and effectiveness of OBV/PTV/r/DSV ± RBV therapy in real-world setting. We analyzed a cohort of patients with genotype 1 infection treated with OBV/PTV/r/DSV ± RBV. Data on demographics, clinical features, safety, and virological response were retrospectively collected from 21 centers in Latin America. A total of 96 patients received OBV/PTV/r/DSV, associated with RBV in 68% of the cases. Most were genotype 1b (80%), 56 (58%) had cirrhosis, and 45 (47%) failed prior HCV treatment. Adverse events occurred in 62% of patients. The most common adverse events were pruritus (21%), hyperbilirubinemia (17%), and asthenia (17%). Five patients discontinued therapy prematurely due to hepatic decompensation, three of them were Child-Pugh B at baseline and one patient died due to multi-organ failure. Follow up HCV-RNA 12 weeks after completion of therapy was evaluated in all the patients and sustained virologic response rate was 97%. No virologic breakthrough was detected. Our study confirms that OBV/PTV/r/DSV treatment is highly effective in patients with chronic HCV without cirrhosis or with Child-Pugh A cirrhosis in non-European populations. Adverse events were often mild and rarely led to treatment discontinuation except for patients with Child-Pugh B cirrhosis or with previous history of hepatic decompensation. These results can support the development of public strategies to expand the access of OBV/PTV/r + DSV and other DAAs combinations in order to reduce the burden of HCV infection in our region.", "affiliations": "Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Pilar, Argentina.;Sección Hepatología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.;Fundación Sayani, San Salvador de Jujuy, Argentina.;Instituto Chileno Japonés de Enfermedades Digestivas, Hospital San Borja Arriaran, Santiago, Chile.;Latin American Liver Research Educational and Awarness Network (LALREAN).;Latin American Liver Research Educational and Awarness Network (LALREAN).;Instituto Chileno Japonés de Enfermedades Digestivas, Hospital San Borja Arriaran, Santiago, Chile.;Instituto Chileno Japonés de Enfermedades Digestivas, Hospital San Borja Arriaran, Santiago, Chile.;Clínica Universitaria Colombia y Centro de Enfermedades Hepáticas y Digestivas (CEHYD), Bogotá, Colombia.;Unidad de Hepatitis Virales de FUNCEI, Buenos Aires, Argentina.;Sección Hepatología, Hospital Dr. Carlos B. Udaondo, Buenos Aires, Argentina.;Sección Hepatología, Hospital Dr. Carlos B. Udaondo, Buenos Aires, Argentina.;Unidad de Hígado y Trasplante Hepático, Hospital Alemán, Buenos Aires, Argentina.;Clínica de Gastroenterología, Hospital de Clínicas, Montevideo, Uruguay.;Latin American Liver Research Educational and Awarness Network (LALREAN).;Hepatología y Trasplante Hepático, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.;Latin American Liver Research Educational and Awarness Network (LALREAN).;FUNDIEH y HPR-Grupo Gamma, Rosario, Argentina.;Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia.;Sección Hepatología, Hospital Dr. Carlos B. Udaondo, Buenos Aires, Argentina.;Trasplante Hepático, Hospital Italiano de Mendoza, Mendoza, Argentina.;Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Pilar, Argentina.;Unidad de Hígado, Hospital Francisco J. Muñiz, Buenos Aires, Argentina.;Sección Hepatología, Sanatorio Municipal Dr. Julio Méndez, Buenos Aires, Argentina.;Universidad Nacional de Rosario, Rosario, Argentina.;Sanatorio Mitre, Buenos Aires, Argentina.;Unidad de Hígado y Trasplante Hepático, Hospital Universitario Austral, Pilar, Argentina.", "authors": "Mendizabal|Manuel|M|0000-0002-7026-9908;Haddad|Leila|L|;Gallardo|Patricia E|PE|;Ferrada|Alejandro|A|;Soza|Alejandro A|AA|;Adrover|Raul|R|;Aravena|Edmundo|E|;Roblero|Juan P|JP|;Prieto|Jhon|J|;Vujacich|Claudia|C|;Romero|Gustavo|G|;Muñoz|Alberto|A|;Anders|Margarita|M|;Hernández|Nelia|N|;Coccozella|Daniel|D|;Gruz|Fernando|F|;Reggiardo|Maria V|MV|;Ruf|Andres E|AE|;Varón|Adriana|A|;Cartier|Mariano|M|;Pérez Ravier|Roberto|R|;Ridruejo|Ezequiel|E|;Peralta|Mirta|M|;Poncino|Daniel|D|;Vorobioff|Julio|J|;Aballay Soteras|Gabriel|G|;Silva|Marcelo O|MO|", "chemical_list": "D000998:Antiviral Agents", "country": "United States", "delete": false, "doi": "10.1002/jmv.24816", "fulltext": null, "fulltext_license": null, "issn_linking": "0146-6615", "issue": "89(9)", "journal": "Journal of medical virology", "keywords": "antiviral agents; disease control; hepatitis C virus; public policy", "medline_ta": "J Med Virol", "mesh_terms": "D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005838:Genotype; D016174:Hepacivirus; D019698:Hepatitis C, Chronic; D006801:Humans; D007843:Latin America; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult", "nlm_unique_id": "7705876", "other_id": null, "pages": "1590-1596", "pmc": null, "pmid": "28370222", "pubdate": "2017-09", "publication_types": "D016428:Journal Article; D016448:Multicenter Study", "references": null, "title": "Ombitasvir/paritaprevir/ritonavir/dasabuvir ± ribavirin is safe and effective in HCV-infected patients in a real-life cohort from Latin America.", "title_normalized": "ombitasvir paritaprevir ritonavir dasabuvir ribavirin is safe and effective in hcv infected patients in a real life cohort from latin america" }

[ { "companynumb": "AR-LANNETT COMPANY, INC.-AR-2017LAN001283", "fulfillexpeditecriteria": "1", "occurcountry": "AR", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "LOPINAVIR\\RITONAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "207407", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIRETROVIRAL THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOPINAVIR AND RITONAVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "OMBITASVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C VIRUS TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMBITASVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "RIBAVIRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C VIRUS TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIBAVIRIN." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "RIBAVIRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIRETROVIRAL THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIBAVIRIN." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LOPINAVIR\\RITONAVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "207407", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C VIRUS TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOPINAVIR AND RITONAVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DASABUVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C VIRUS TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DASABUVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PARITAPREVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "150 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C VIRUS TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "150", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PARITAPREVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "DASABUVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIRETROVIRAL THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DASABUVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "OMBITASVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIRETROVIRAL THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMBITASVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PARITAPREVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIRETROVIRAL THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PARITAPREVIR" } ], "patientagegroup": null, "patientonsetage": "66", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "MENDIZABAL M, HADDAD L, GALLARDO PE, FERRADA A, SOZA AA, ADROVER R, ET AL. OMBITASVIR/PARITAPREVIR/RITONAVIR/DASABUVIR +/- RIBAVIRIN IS SAFE AND EFFECTIVE IN HCV-INFECTED PATIENTS IN A REAL-LIFE COHORT FROM LATIN AMERICA. J-MED-VIROL. 2017;89(9):1590-1596", "literaturereference_normalized": "ombitasvir paritaprevir ritonavir dasabuvir ribavirin is safe and effective in hcv infected patients in a real life cohort from latin america", "qualification": "3", "reportercountry": "AR" }, "primarysourcecountry": "AR", "receiptdate": "20171229", "receivedate": "20171229", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14336837, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180321" }, { "companynumb": "AR-LANNETT COMPANY, INC.-AR-2017LAN001282", "fulfillexpeditecriteria": "1", "occurcountry": "AR", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "OMBITASVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIRETROVIRAL THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMBITASVIR" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "DASABUVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIRETROVIRAL THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DASABUVIR" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "OMBITASVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "25 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C VIRUS TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "OMBITASVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PARITAPREVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "150 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C VIRUS TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "150", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PARITAPREVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LOPINAVIR\\RITONAVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "207407", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIRETROVIRAL THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOPINAVIR AND RITONAVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PARITAPREVIR" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIRETROVIRAL THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PARITAPREVIR" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "DASABUVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "250 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C VIRUS TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "250", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DASABUVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "RIBAVIRIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIRETROVIRAL THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIBAVIRIN." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "LOPINAVIR\\RITONAVIR" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "207407", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C VIRUS TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOPINAVIR AND RITONAVIR" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "RIBAVIRIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEPATITIS C VIRUS TEST POSITIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "RIBAVIRIN." } ], "patientagegroup": null, "patientonsetage": "50", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pneumonia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Hepatic failure", "reactionmeddraversionpt": "20.1", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "MENDIZABAL M, HADDAD L, GALLARDO PE, FERRADA A, SOZA AA, ADROVER R, ET AL. OMBITASVIR/PARITAPREVIR/RITONAVIR/DASABUVIR +/- RIBAVIRIN IS SAFE AND EFFECTIVE IN HCV-INFECTED PATIENTS IN A REAL-LIFE COHORT FROM LATIN AMERICA. J-MED-VIROL. 2017;89(9):1590-1596", "literaturereference_normalized": "ombitasvir paritaprevir ritonavir dasabuvir ribavirin is safe and effective in hcv infected patients in a real life cohort from latin america", "qualification": "3", "reportercountry": "AR" }, "primarysourcecountry": "AR", "receiptdate": "20171229", "receivedate": "20171229", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14336785, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180321" } ]

{ "abstract": "OBJECTIVE\nRectal cancer patients who present with peritumoral abscesses and fistulas at the time of diagnosis may be denied chemoradiotherapy (CRT) as the safety is unknown. The aim of this study was to investigate the safety of preoperative CRT in this patient group.\n\n\nMETHODS\nWe performed a retrospective nested case-control study to compare outcomes between patients with locally advanced rectal cancer with peritumoral abscesses and fistulas (study group) and patients with T4 locally advanced rectal cancer with no evidence of abscesses and fistulas (control group). These groups were matched by treatment center and radiotherapy delivery method. All patients received 50-54 Gy of conventionally fractionated RT with concurrent chemotherapy. Primary endpoint was grade 3-5 toxicity (by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE). Secondary endpoints included postoperative morbidity, pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) at 2 years.\n\n\nRESULTS\nA total of 33 patients were included in each group. Grade 3 toxicity was observed in 2 (6.1%) patients in the study group and 4 (12.1%) patients in the control group (p = 0.672). No patients developed grade 4-5 toxicity. Grade 3-4 Clavien-Dindo complications were observed in 5 (15.2%) patients in the study group and in 6 (18.2%) patients in the control group (p = 1.0). Pathologic CR was achieved in 3 (9.1%) and 5 (15.2%) patients, respectively (p = 0.708). Two-year OS was 78.3% vs. 81.8% (p = 0.944), 2‑year DFS was 62.8% vs. 69.7% (p = 0.693), respectively.\n\n\nCONCLUSIONS\nThe presence of peritumoral abscesses and fistulas in patients with locally advanced rectal cancer is not associated with increased toxicity or inferior clinical outcomes after preoperative CRT.", "affiliations": "N.N.Blokhin National Medical Research Center of Oncology, 23, Kashirskoe shosse, 115478, Moscow, Russian Federation. ss.netoncology@gmail.com.;\"PET-technology\" cancer center, 26, 50 let VLKSM st., 142110, Podolsk, Russian Federation.;N.N.Blokhin National Medical Research Center of Oncology, 23, Kashirskoe shosse, 115478, Moscow, Russian Federation.;N.N.Blokhin National Medical Research Center of Oncology, 23, Kashirskoe shosse, 115478, Moscow, Russian Federation.;N.N.Blokhin National Medical Research Center of Oncology, 23, Kashirskoe shosse, 115478, Moscow, Russian Federation.;A.F. Tsyb Medical Radiological Research Center, Zhukov st., 249031, Obninsk, Russian Federation.;Moscow city oncological hospital № 1, Baumanskaya 17/1, 105005, Moscow, Russian Federation.;Stavropol regional oncological dispensary, 182A, Oktyabrskaya st., 355047, Stavropol, Russian Federation.;Krasnodar regional oncological dispensary, 146, Dmitrova st., 350040, Krasnodar, Russian Federation.;Bashkir regional oncological dispensary, 73/1, Prospekt Octyabrya, 450054, Ufa, Russian Federation.;N.N.Blokhin National Medical Research Center of Oncology, 23, Kashirskoe shosse, 115478, Moscow, Russian Federation.", "authors": "Gordeyev|Sergey|S|http://orcid.org/0000-0002-9303-8379;Ivanov|Valerii|V|http://orcid.org/0000-0003-3028-7578;Fedianin|Mikhail|M|http://orcid.org/0000-0001-5615-7806;Chernikh|Marina|M|http://orcid.org/0000-0003-4944-4035;Kozlov|Nikolay|N|http://orcid.org/0000-0003-3852-3969;Petrov|Leonid|L|;Erygin|Dmitriy|D|http://orcid.org/0000-0002-7278-8525;Gridasov|Ivan|I|;Kaushanskiy|Valery|V|http://orcid.org/0000-0001-7839-6410;Feoktistov|Dmitry|D|;Mamedli|Zaman|Z|http://orcid.org/0000-0002-9289-1247", "chemical_list": null, "country": "Germany", "delete": false, "doi": "10.1007/s00066-021-01878-y", "fulltext": null, "fulltext_license": null, "issn_linking": "0179-7158", "issue": null, "journal": "Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]", "keywords": "Perianal fistula; Rectal cancer with abscess; Rectovaginal fistula; Rectovesical fistula; Tumor-associated fistula", "medline_ta": "Strahlenther Onkol", "mesh_terms": null, "nlm_unique_id": "8603469", "other_id": null, "pages": null, "pmc": null, "pmid": "34825253", "pubdate": "2021-11-25", "publication_types": "D016428:Journal Article", "references": "27332723;29394675;29394660;28133087;25731360;23267942;29394765;24394003;24394002;25731358;25731359;29063019;33108641;29184696;33813405", "title": "Neoadjuvant chemoradiotherapy for locally advanced rectal cancer with peritumoral abscesses and fistulas.", "title_normalized": "neoadjuvant chemoradiotherapy for locally advanced rectal cancer with peritumoral abscesses and fistulas" }

[ { "companynumb": "RU-ROCHE-3023598", "fulfillexpeditecriteria": "1", "occurcountry": null, "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CAPECITABINE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": "20896", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Tablet", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Rectal cancer", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "2", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "825", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CAPECITABINE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Leukopenia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Neutropenia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Thrombocytopenia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Anaemia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Fatigue", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Proctitis", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Vomiting", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Radiation skin injury", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cystitis", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Aspartate aminotransferase", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Alanine aminotransferase", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Gordeyev S, Ivanov V, Fedianin M, Chernikh M, Kozlov N, Petrov L, Erygin D, Gridasov I, Kaushanskiy V, Feoktistov D and Mamedli Z. Neoadjuvant chemoradiotherapy for locally advanced rectal cancer with peritumoral abscesses and fistulas. Strahlentherapie und Onkologie 2022 Feb;198 (2):201-8.", "literaturereference_normalized": "neoadjuvant chemoradiotherapy for locally advanced rectal cancer with peritumoral abscesses and fistulas", "qualification": "3", "reportercountry": "RU" }, "primarysourcecountry": "RU", "receiptdate": "20220222", "receivedate": "20220222", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 20501274, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" } ]

{ "abstract": "OBJECTIVE\nTo report a case of hypothermia in a patient with intellectual disability treated with thioridazine.\n\n\nCONCLUSIONS\nA 59-year-old female presented to the emergency department with altered mental status, generalized weakness, chills, and fatigue and was diagnosed with a urinary tract infection. Upon completion of a history and physical examination, the patient was found to be hypothermic with a temperature of 91 F. A Bair Hugger protocol was initiated to manage hypothermia, and a taper schedule for thioridazine was initiated as it was identified as a possible culprit for the patient's hypothermia. According to the Naranjo probability scale, thioridazine was a possible cause of this adverse effect. Other patient-specific risk factors for hypothermia were evaluated and ruled out.\n\n\nCONCLUSIONS\nThis case indicates a possible correlation between hypothermia and the use of phenothiazine antipsychotics such as thioridazine. Appropriate measures, including early detection and identification of possible causative agents, should be taken to prevent and treat this adverse event in patients taking these medications, specifically in patients with the inability to participate in self-care.", "affiliations": "Presbyterian College School of Pharmacy, Clinton, SC, USA nhgoodbar@presby.edu.;Presbyterian College School of Pharmacy, Clinton, SC, USA.;Marshall Pickens Hospital/Greenville Health System, Greenville, SC, USA.;Presbyterian College School of Pharmacy, Clinton, SC, USA.;Presbyterian College School of Pharmacy, Clinton, SC, USA.", "authors": "Goodbar|Nancy H|NH|;Foushee|Jaime A|JA|;Nash|Kathryn|K|;Connolly|Lindsey A|LA|;Webster|L Markie|LM|", "chemical_list": "D014150:Antipsychotic Agents; D013881:Thioridazine", "country": "United States", "delete": false, "doi": "10.1177/0897190015623154", "fulltext": null, "fulltext_license": null, "issn_linking": "0897-1900", "issue": "29(3)", "journal": "Journal of pharmacy practice", "keywords": "internal medicine; medication safety", "medline_ta": "J Pharm Pract", "mesh_terms": "D014150:Antipsychotic Agents; D005260:Female; D006801:Humans; D007035:Hypothermia; D008607:Intellectual Disability; D008875:Middle Aged; D013881:Thioridazine", "nlm_unique_id": "8900945", "other_id": null, "pages": "250-2", "pmc": null, "pmid": "26739480", "pubdate": "2016-06", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Hypothermia Associated With Thioridazine Use in an Intellectually Disabled Patient.", "title_normalized": "hypothermia associated with thioridazine use in an intellectually disabled patient" }

[ { "companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2016US-118615", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "ESTROGENS, CONJUGATED" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "0.45/1.5 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CONJUGATED ESTROGENS" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "SENNA LEAF\\SENNOSIDES\\SENNOSIDES A AND B" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "8.6 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8.6", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SENNA" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LEVETIRACETAM" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "750 MG, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "12", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "750", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVETIRACETAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "1 MG, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "LEVOTHYROXINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LEVOTHYROXINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ATORVASTATIN" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG, QD (AT BEDTIME)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ATORVASTATIN" }, { "actiondrug": null, "activesubstance": null, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, BID", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "12", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CALCIUM AND VITAMIN D SUPPLEMENTATION" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MICONAZOLE NITRATE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CREAM", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MICONAZOLE NITRATE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "THIORIDAZINE" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "089953", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MG, TID", "drugenddate": null, "drugenddateformat": null, "drugindication": "AGITATION", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "20131105", "drugstartdateformat": "102", "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THIORIDAZINE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "200 MG, PRN", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "200", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "THIORIDAZINE" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "089953", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG, TID", "drugenddate": "20131104", "drugenddateformat": "102", "drugindication": "INTELLECTUAL DISABILITY", "drugintervaldosagedefinition": "805", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "2013", "drugstartdateformat": "602", "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THIORIDAZINE" }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "THIORIDAZINE" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "089953", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PSYCHOTIC DISORDER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "THIORIDAZINE" } ], "patientagegroup": null, "patientonsetage": "59", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Hypothermia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2013" } }, "primarysource": { "literaturereference": "GOODBAR NH, FOUSHEE JA, NASH K, CONNOLLY LA, WEBSTER LM. HYPOTHERMIA ASSOCIATED WITH THIORIDAZINE USE IN AN INTELLECTUALLY DISABLED PATIENT. J PHARM PRACT. 2014;29(3):250-252", "literaturereference_normalized": "hypothermia associated with thioridazine use in an intellectually disabled patient", "qualification": "2", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20171117", "receivedate": "20160622", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12487640, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180320" } ]

{ "abstract": "OBJECTIVE\nA therapeutic failure (TF) is defined as a failure to accomplish the goals of treatment attributable to inadequate therapy, a drug-drug interaction that results in a subtherapeutic level for a drug, or medication nonadherence. The objective of this study was to evaluate the prevalence of and factors associated with TF-related hospitalizations in older adults.\n\n\nMETHODS\nThis investigation was a retrospective cohort study.\n\n\nMETHODS\nThis study was conducted within a university-based hospital setting.\n\n\nMETHODS\nThis investigation included patients with a primary care physician from the University of Pittsburgh Medical Center (UPMC) Senior Care Institute admitted to any UPMC hospital between September 1, 2011, and December 1, 2011.\n\n\nMETHODS\nChart abstracts of patient records were screened for a TF using a validated tool called the Therapeutic Failure Questionnaire (TFQ). Covariate data were also obtained. Descriptive statistics and bivariate analyses using Fisher's exact tests were conducted to assess the association between the covariates and the primary outcome.\n\n\nMETHODS\nThe primary outcome was the presence of a TF as measured by the TFQ. Secondary outcomes included associations between covariates and the presence of a TF.\n\n\nRESULTS\nOf the 93 hospitalizations screened, 57 met inclusion criteria, and 18% of hospitalizations were as a result of preventable TFs. On bivariate analyses, both congestive heart failure (P = 0.03) and dependency for medication management (P = 0.04) were significantly associated with occurrence of TF.\n\n\nCONCLUSIONS\nTFs are a potentially preventable cause of hospitalization in the elderly population and are commonly caused by omission of therapy.", "affiliations": "Department of Pharmacy Practice, Thomas Jefferson University, Jefferson School of Pharmacy, Philadelphia, Pennsylvania, USA.", "authors": "Patel|Roshni S|RS|;Marcum|Zachary A|ZA|;Peron|Emily P|EP|;Ruby|Christine M|CM|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.4140/TCP.n.2014.376.", "fulltext": null, "fulltext_license": null, "issn_linking": "0888-5109", "issue": "29(6)", "journal": "The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists", "keywords": null, "medline_ta": "Consult Pharm", "mesh_terms": "D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006333:Heart Failure; D006760:Hospitalization; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D017211:Treatment Failure", "nlm_unique_id": "9013983", "other_id": null, "pages": "376-86", "pmc": null, "pmid": "25202891", "pubdate": "2014-06", "publication_types": "D016428:Journal Article", "references": null, "title": "Prevalence of and factors associated with therapeutic failure-related hospitalizations in the elderly.", "title_normalized": "prevalence of and factors associated with therapeutic failure related hospitalizations in the elderly" }

[ { "companynumb": "US-B.I. PHARMACEUTICALS,INC./RIDGEFIELD-2015-BI-32264GD", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "METOPROLOL" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METOPROLOL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TELMISARTAN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "020850", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MICARDIS" } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug dose omission", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Treatment failure", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PATEL R,MARCUM Z,PERON E,RUBY C. PREVALENCE OF AND FACTORS ASSOCIATED WITH THERAPEUTIC FAILURE-RELATED HOSPITALIZATIONS IN THE ELDERLY. CONSULTANT PHARM 2014 JUN;29:6:376-386.", "literaturereference_normalized": "prevalence of and factors associated with therapeutic failure related hospitalizations in the elderly", "qualification": "3", "reportercountry": "COUNTRY NOT SPECIFIED" }, "primarysourcecountry": "US", "receiptdate": "20150618", "receivedate": "20150618", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 11200318, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150821" }, { "companynumb": "US-PFIZER INC-2019174437", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "FUROSEMIDE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "018667", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "CARDIAC FAILURE CONGESTIVE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FUROSEMIDE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Treatment noncompliance", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Treatment failure", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "PATEL, R.. PREVALENCE OF AND FACTORS ASSOCIATED WITH THERAPEUTIC FAILURE-RELATED HOSPITALIZATIONS IN THE ELDERLY. THE CONSULTANT PHARMACIST. 2014?29 (6):376-386", "literaturereference_normalized": "prevalence of and factors associated with therapeutic failure related hospitalizations in the elderly", "qualification": "2", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190425", "receivedate": "20190425", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 16239583, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20190711" } ]

{ "abstract": "Adenovirus is a rare cause of hemorrhagic cystitis in the transplant population. We present a case of a forty-one-year-old man with end-stage renal disease who underwent living unrelated donor kidney transplant in 2016. In 2018 he presented with acute onset gross hematuria and dysuria, with serologic testing and immunohistochemical stains of biopsy specimens positive for adenovirus. He was treated with reduction in immunosuppression, cystoscopy with evacuation of clots, and alum bladder irrigation. His hematuria resolved almost immediately with no recurrence to date. This case demonstrates the efficacy and safety of alum irrigation in patients with adenovirus hemorrhagic cystitis.", "affiliations": "MedStar Georgetown University Hospital, USA.;MedStar Georgetown University Hospital, USA.;MedStar Georgetown University Hospital, USA.", "authors": "Egan|Jillian|J|;Vranic|Gayle|G|;Ghasemian|Seyed Reza|SR|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1016/j.eucr.2019.101042", "fulltext": "\n==== Front\nUrol Case RepUrol Case RepUrology Case Reports2214-4420Elsevier S2214-4420(19)30387-010.1016/j.eucr.2019.101042101042Inflammation and InfectionAlum irrigation for the treatment of adenovirus induced hemorrhagic cystitis in a kidney transplant recipient Egan Jillian Jillian.Egan@Gunet.Georgetown.edu∗Vranic Gayle Gayle.M.Vranic@Gunet.Georgetown.eduGhasemian Seyed Reza Seyed.Ghasemian@Medstar.netMedStar Georgetown University Hospital, USA∗ Corresponding author. Jillian.Egan@Gunet.Georgetown.edu10 10 2019 5 2020 10 10 2019 30 10104219 9 2019 7 10 2019 8 10 2019 © 2019 Published by Elsevier Inc.2019This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Adenovirus is a rare cause of hemorrhagic cystitis in the transplant population. We present a case of a forty-one-year-old man with end-stage renal disease who underwent living unrelated donor kidney transplant in 2016. In 2018 he presented with acute onset gross hematuria and dysuria, with serologic testing and immunohistochemical stains of biopsy specimens positive for adenovirus. He was treated with reduction in immunosuppression, cystoscopy with evacuation of clots, and alum bladder irrigation. His hematuria resolved almost immediately with no recurrence to date. This case demonstrates the efficacy and safety of alum irrigation in patients with adenovirus hemorrhagic cystitis.\n==== Body\nIntroduction\nAdenovirus is a common culprit in respiratory and gastrointestinal illness, usually affecting children and military recruits. It is also an important cause of morbidity and mortality in the immunosuppressed. Acute hemorrhage cystitis from adenovirus has been reported following bone marrow transplant but is rarely reported following solid organ transplant. It typically presents with fever, dysuria, urinary frequency, and gross hematuria. Treatment strategies have included adjustments of immunosuppression, treatment with antivirals, and continuous bladder irrigation with varying degrees of success. We present a case report of a renal transplant recipient with hemorrhagic cystitis secondary to adenovirus which resolved completely with alum irrigation.\n\nCase presentation\nA forty-one-year-old man with end stage renal disease from IgA nephropathy underwent living unrelated donor kidney transplant. Induction with alemtuzumab was followed by maintenance immunosuppression with tacrolimus and mycophenolate mofetil (MMF). Twenty-two months after transplant he presented with acute onset of dysuria and gross hematuria with clots. Renal function was at baseline with a serum creatinine of 1.1–1.2 mg/dL. Urinalysis and microscopy showed >50 WBC and >50 RBC per high power field and trace leukocyte esterase with no bacteria. Bacterial urine culture had no growth. Cystoscopy demonstrated a diffusely erythematous bladder with areas of hemorrhage without any discrete bladder tumors(Fig. 1). Random biopsies were taken. He was started on continuous bladder irrigation with 1% alum. Hematuria resolved within 24 h.Fig. 1 Cystoscopy demonstrating diffusely erythematous bladder mucosa.\n\nFig. 1\n\nPathology revealed totally denuded bladder mucosa, markedly engorged capillaries in the superficial submucosa and focal hemorrhage. Viral immunohistochemistry revealed stromal cells and vascular endothelial cells positive for adenovirus (Fig. 2). Serum quantitative DNA by PCR for adenovirus was highly positive (53,208 copies/mL) and negative for cytomegalovirus (CMV), BK virus, and herpes simplex virus (HSV). Foley catheter removed and patient discharged on post-operative day two. His MMF was discontinued, low dose prednisone was started, and tacrolimus was continued to target 12-h trough levels of 5–8 ng/mL. Adenovirus was detectable (32,086 copies/mL) 6 weeks after treatment and undetectable at 8 weeks and on all subsequent serum PCR assays. Low dose MMF at 250 mg orally twice daily was restarted three months after diagnosis. Renal function remained stable with serum creatinine of 1.1 mg/dL and no recurrence of hematuria at 18 months.Fig. 2 Immunohistochemistry stain of bladder biopsy specimen revealing adenovirus positive cells.\n\nFig. 2\n\nDiscussion\nAdenovirus is a non-enveloped, double-stranded DNA virus. It is endemic in the population and 80% of children have antibody to one or more serotypes by age 5. It has been known to cause respiratory illness, gastroenteritis, and conjunctivitis but disease is typically mild in immunocompetent hosts. In immunosuppressed populations illness can be prolonged, severe, and sometimes fatal. In these patients, infection can be related to reactivation of the virus as well as primary infection. One unusual sequelae is hemorrhagic cystitis which was first reported in 1968 in children.1 Typically, it presents with fever, gross hematuria, and dysuria and can be associated with acute kidney injury in the setting of negative bacterial urine cultures.\n\nAdenoviral hemorrhagic cystitis is well reported in stem cell transplant but infrequently reported in solid organ transplants, specifically kidney transplants. The incidence of adenovirus infection in kidney transplant recipients has been reported as 6.5%2 but the incidence of hemorrhagic cystitis from adenovirus is much lower. Mechanisms of spread to the bladder are unknown. Hypotheses include viral particles from the kidney travelling to the bladder in urine, retrograde spread through the urethra, pelvic lymphatic spread from the gastrointestinal tract, or direct hematogenous spread.1\n\nThe differential diagnosis for gross hematuria following transplant is broad and adenoviral infection is difficult to diagnose. Viral urine cultures have low sensitivity and therefore a negative viral culture does not exclude the possibility of adenovirus infection. Serologic tests should be performed with PCR.3 On cystoscopy, bladder mucosa appears diffusely erythematous and hyperemic. Pathologic analysis shows cystitis, usually with an erosive component. If performed, immunohistochemical evaluation demonstrates large nuclei with basophilic inclusion bodies consistent with adenovirus.3\n\nReduction in pharmacologic immunosuppression permits T cell recovery allowing the immune system to mount an appropriate response to adenovirus.3 Antiviral agents such as ribavirin and cidofovir1 have been used. Treatment with cidofovir can be limited by nephrotoxicity. Intractable hematuria warrants aggressive intervention and cystoscopy with clot evacuation and fulguration with continuous bladder irrigation are sometimes necessary. Irrigation can be performed with normal saline, aminocaproic acid, alum, and formalin. Sparse literature is available on the use of alum in these patients.1\n\nAlum irrigation was first reported in 1982 in the treatment of six patients with hemorrhagic cystitis of different etiologies. A 1% alum solution is created by mixing 50g of aluminum potassium sulfate with 5L of sterile water which is instilled as continuous bladder irrigation at a rate of 300 cc/hr. Alum is well tolerated and unlike formalin instillation, which requires instillation in the operating room under general anesthesia, can be delivered bedside. Alum is renally excreted and caution should be used in patients with impaired renal function as aluminum toxicity resulting in neurologic symptoms has been reported with inappropriate use.4 The mechanism of action is proposed to be the induction of protein precipitation at the cell surface, decreased capillary permeability, vasoconstriction, hardening of the capillary endothelium, and a reduction in edema and inflammation.4 Studies have shown the preservation of the mucosal integrity after alum irrigation, which is why alum can be delivered safely in the setting of vesicoureteral reflux.5 Therefore, no cystogram is needed. This is important in kidney transplant patients because many have some degree of reflux.\n\nWesterman et al. reported on the efficacy and safety of alum irrigation in the general population. In their series alum irrigation was successful in 60% of patients with mild adverse effects. Of those who responded to alum irrigation, response was durable in 54%, requiring no further hospitalizations for hemorrhagic cystitis at a median follow up of 16 months.4 To our knowledge, this is the first report of its use in adenovirus associated hemorrhagic cystitis after renal transplant.\n\nConclusion\nOur case report suggests alum irrigation is a safe and effective management strategy for gross hematuria secondary to adenovirus hemorrhagic cystitis.\n==== Refs\nReferences\n1 Londergan T.A. Walzak M.P. Hemorrhagic cystitis due to adenovirus infection following bone marrow transplantation J Urol 1994 \n2 Ortiz M. Ulloa C. Troncoso P. Rabagliati R. Jara A. Hemorrhagic cystitis secondary to adenovirus infection in a kidney transplant recipient: case report Transplant Proc 2009 \n3 Majorant D. Qiu F. Kalil A.C. Wilson N. Florescu D.F. Adenovirus—a deadly disease in the solid organ transplant population: risk factors and outcomes Transplant Proc 2018 \n4 Westerman M.E. Boorjian S.A. Linder B.J. Safety and efficacy of intravesical alum for intractable hemorrhagic cystitis: a contemporary evaluation Int Braz J Urol 2016 \n5 Goel A.K. Rao M.S. Bhagwat A.G. Vaidyanathan S. Goswami A.K. Sen T.K. Intravesical irrigation with alum for the control of massive bladder hemorrhage J Urol 1985\n\n", "fulltext_license": "CC BY-NC-ND", "issn_linking": "2214-4420", "issue": "30()", "journal": "Urology case reports", "keywords": null, "medline_ta": "Urol Case Rep", "mesh_terms": null, "nlm_unique_id": "101626357", "other_id": null, "pages": "101042", "pmc": null, "pmid": "32055446", "pubdate": "2020-05", "publication_types": "D002363:Case Reports", "references": "3999219;19716001;30577268;8126773;27509371", "title": "Alum irrigation for the treatment of adenovirus induced hemorrhagic cystitis in a kidney transplant recipient.", "title_normalized": "alum irrigation for the treatment of adenovirus induced hemorrhagic cystitis in a kidney transplant recipient" }

[ { "companynumb": "NVSC2020US024173", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "65379", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": "65379", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "65461", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "65461", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, 12-H TROUGH LEVELS OF 5-8 NG/ML", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." } ], "patientagegroup": null, "patientonsetage": "41", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Haematuria", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Adenovirus infection", "reactionmeddraversionpt": "22.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Dysuria", "reactionmeddraversionpt": "22.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "EGAN J, VRANIC G, GHASEMIAN SR. ALUM IRRIGATION FOR THE TREATMENT OF ADENOVIRUS INDUCED HEMORRHAGIC CYSTITIS IN A KIDNEY TRANSPLANT RECIPIENT. UROLOGY CASE REPORTS. 2020?30:1-4", "literaturereference_normalized": "alum irrigation for the treatment of adenovirus induced hemorrhagic cystitis in a kidney transplant recipient", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200202", "receivedate": "20200202", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 17358792, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20200409" } ]

{ "abstract": "To report a case of arachnoiditis as a complication of epidural blood patch procedures and to systematically review the diagnostic workup, clinical outcomes, and treatment modalities reported in the literature.\n\n\n\nEpidural blood patching is an effective treatment for low-pressure headache secondary to spontaneous cerebrospinal fluid leak or iatrogenic post-dural puncture. Spontaneous intracranial hypotension is believed to be a rare headache disorder, but recently has been diagnosed at higher frequencies, making it an important differential diagnosis for intractable headaches. Arachnoiditis has surfaced as a rare complication of epidural blood patching. Symptom presentation does not always correlate with evidence of meningeal enhancement on imaging. Optimal methods for treatment remain largely unknown.\n\n\n\nDatabases Embase and PubMed were searched for all published studies on arachnoiditis post-epidural blood patch using a combination of the following medical subject headings and keywords: arachnoiditis, arachnoid inflammation, adverse event, and epidural blood patch. All original English-language articles that described arachnoid and/or meningeal inflammation in conjunction with epidural blood patch procedures were included for analysis. Title and abstract screening, data extraction, and risk of bias assessment were conducted independently and in duplicate by two reviewers.\n\n\n\nSeven other cases of arachnoiditis post-blood patch placement have been documented, most of which were diagnosed via magnetic resonance imaging. Six of these were a result of a spinal-epidural anesthesia for labor and delivery. Common symptoms reported were headache, back and radicular pain, paresthesia, and motor weakness. There are currently no proven consensus-based treatment recommendations available. While intravenous methylprednisolone followed by oral prednisone taper was found to be effective in the case presented, the benefit of other multi-modal therapies was unclear.\n\n\n\nHeadache specialists who treat postural headache should be aware of arachnoiditis as a potentially severe complication of epidural blood patch. The case presented is the first of its kind to report arachnoiditis as a complication of high-volume blood patch for the treatment of spontaneous intracranial hypotension. More studies are required to determine suitable treatment options for post-epidural blood patch arachnoiditis.", "affiliations": "Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.;Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.;Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.;Division of Headache and Neuro-Ophthalmology, University of Utah School of Medicine, Salt Lake City, UT, USA.;Division of Neuroradiology Imaging, University of Utah School of Medicine, Salt Lake City, UT, USA.;Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.", "authors": "Villani|Linda A|LA|;Digre|Kathleen B|KB|;Cortez|Melissa M|MM|;Bokat|Christina|C|;Rassner|Ulrich A|UA|;Ozudogru|Seniha N|SN|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.1111/head.14076", "fulltext": null, "fulltext_license": null, "issn_linking": "0017-8748", "issue": "61(2)", "journal": "Headache", "keywords": "arachnoid Inflammation; arachnoiditis; epidural blood patch; intracranial hypotension", "medline_ta": "Headache", "mesh_terms": null, "nlm_unique_id": "2985091R", "other_id": null, "pages": "244-252", "pmc": null, "pmid": "33583044", "pubdate": "2021-02", "publication_types": "D016428:Journal Article; D016454:Review", "references": null, "title": "Arachnoiditis, a complication of epidural blood patch for the treatment of low-pressure headache: A case report and systematic review.", "title_normalized": "arachnoiditis a complication of epidural blood patch for the treatment of low pressure headache a case report and systematic review" }

[ { "companynumb": "US-STRIDES ARCOLAB LIMITED-2021SP006802", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "211666", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEADACHE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "ACETAMINOPHEN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEADACHE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ACETAMINOPHEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CAFFEINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "HEADACHE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CAFFEINE." } ], "patientagegroup": null, "patientonsetage": "30", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Maternal exposure during pregnancy", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "VILLANI LA, DIGRE KB, CORTEZ MM, BOKAT C, RASSNER UA, OZUDOGRU SN.. ARACHNOIDITIS, A COMPLICATION OF EPIDURAL BLOOD PATCH FOR THE TREATMENT OF LOW?PRESSURE HEADACHE: A CASE REPORT AND SYSTEMATIC REVIEW. HEADACHE. 2021?61(2):244?252", "literaturereference_normalized": "arachnoiditis a complication of epidural blood patch for the treatment of low pressure headache a case report and systematic review", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210913", "receivedate": "20210913", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19822974, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" } ]

{ "abstract": "Various adverse events can occur during antineoplastic therapy. A 67-year-old diabetic woman developed an emphysematous urinary tract infection (UTI) associated with chemoradiotherapy for lung cancer. She had received weekly carboplatin plus paclitaxel with thoracic radiotherapy and developed a fever on day 19. Computed tomography showed a large quantity of gas within the urinary tract. She was therefore diagnosed with emphysematous UTI. Poor diabetes control due to the weekly administration of dexamethasone, an existing urinary tract obstruction, and bone marrow suppression were involved in her serious infection. The potential development of emphysematous UTI during chemoradiotherapy should be considered in at-risk patients.", "affiliations": "Division of Respiratory Medicine, Department of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.;Division of Respiratory Medicine, Department of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.;Division of Respiratory Medicine, Department of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.;Division of Respiratory Medicine, Department of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.;Division of Respiratory Medicine, Department of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.", "authors": "Yokoyama|Tetsuya|T|;Shinozaki|Seiji|S|;Arimura|Hidenobu|H|;Nakatomi|Keita|K|;Wataya|Hiroshi|H|", "chemical_list": null, "country": "Switzerland", "delete": false, "doi": "10.1159/000463381", "fulltext": "\n==== Front\nCase Rep OncolCase Rep OncolCROCase Reports in Oncology1662-6575S. Karger AG Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch 10.1159/000463381cro-0010-0239Case ReportEmphysematous Pyelonephritis and Cystitis: Unusual Adverse Events during Concurrent Chemoradiotherapy for Lung Cancer Yokoyama Tetsuya *Shinozaki Seiji Arimura Hidenobu Nakatomi Keita Wataya Hiroshi Division of Respiratory Medicine, Department of Internal Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan*Tetsuya Yokoyama, MD, Division of Respiratory Medicine, Department of Internal Medicine, Saiseikai Fukuoka General Hospital, 1-3-46 Tenjin, Chuo-ku, Fukuoka 810-0001 (Japan), E-Mail yokoyama.tetsuya.1979@gmail.comJan-Apr 2017 9 3 2017 9 3 2017 10 1 239 243 14 2 2017 14 2 2017 Copyright © 2017 by The Author(s)Published by S. Karger AG, Basel2017This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.Various adverse events can occur during antineoplastic therapy. A 67-year-old diabetic woman developed an emphysematous urinary tract infection (UTI) associated with chemoradiotherapy for lung cancer. She had received weekly carboplatin plus paclitaxel with thoracic radiotherapy and developed a fever on day 19. Computed tomography showed a large quantity of gas within the urinary tract. She was therefore diagnosed with emphysematous UTI. Poor diabetes control due to the weekly administration of dexamethasone, an existing urinary tract obstruction, and bone marrow suppression were involved in her serious infection. The potential development of emphysematous UTI during chemoradiotherapy should be considered in at-risk patients.\n\nKey Words\nLung cancerChemoradiotherapyAdverse eventEmphysematous pyelonephritisEmphysematous cystitis\n==== Body\nIntroduction\nSerious infection is one of the most critical adverse events of antineoplastic therapy. Emphysematous urinary tract infection (UTI) is rare and life-threatening and is often associated with poorly controlled diabetes mellitus (DM). We herein report a case of emphysematous UTI that was affected by worsening diabetes control occurring in association with the weekly administration of dexamethasone for antiemesis during chemoradiotherapy.\n\nCase Report\nA 67-year-old diabetic woman, whose hemoglobin A1c level was 7.7%, was being treated with a dipeptidyl peptidase-4 inhibitor. She was found to have anemia (hemoglobin 8.6 g/dL), and subsequent upper gastrointestinal endoscopy revealed gastric cancer with poorly differentiated adenocarcinoma. Computed tomography showed multiple mediastinal lymphadenopathies, right renal aplasia, and left megaureter. Although we could not identify the primary lesion in the lungs and other organs by 18F-fluorodeoxyglucose positron emission tomography, transbronchial needle biopsies of mediastinal lymph nodes revealed metastases of squamous cell carcinoma. Finally, we diagnosed the patient with locally advanced non-small-cell lung cancer (cT0N2M0, cStage IIIA). Urological evaluation revealed congenital right renal aplasia and ruled out ureteral stenosis (such as a stone or neoplasm).\n\nThe patient was admitted for concurrent chemoradiotherapy before surgery for gastric cancer because her lung cancer seemed to be more serious than her gastric cancer. The predefined treatments were as follows: total radiation doses 60 Gy in 2-Gy fractions, and chemotherapy with weekly paclitaxel (40 mg/m2) plus carboplatin (area under the curve: 2). Dexamethasone was administered for antiemesis at 10 mg/day (intravenously) on day 1 and 8 mg/day (orally) on days 2 and 3; this protocol was repeated every week. Her preprandial blood glucose level was elevated beyond 200 mg/dL on days 1–3, despite the administration of sliding-scale insulin therapy.\n\nThe patient had a white blood cell (WBC) count of 3,500 cells/mm3 with 77% neutrophils on day 14. We administered chemotherapeutic agents as planned on day 15. She developed a fever on day 19, but did not complain of any other symptoms. Laboratory tests showed a WBC count of 6,700 cells/mm3 with 96% neutrophils, an elevated C-reactive protein level (17.9 mg/dL), 3+ urine leukocytes, and 1+ urine nitrite. Contrast-enhanced computed tomography showed enlargement of her left kidney compared with the state before chemoradiotherapy as well as a large quantity of gas within the kidney pelvis, ureter, and bladder (Fig. 1). She was diagnosed with emphysematous pyelonephritis and cystitis. Klebsiella pneumoniae was subsequently isolated from urine, but not from blood. Transurethral insertion of a urethral stent and intravenous administration of antibiotics (meropenem followed by oral levofloxacin) resulted in symptom relief and disease remission. Two weeks after the onset of disease, the remaining chemoradiotherapy was restarted and completed with the insertion of a urethral stent.\n\nDiscussion\nWe describe a case of emphysematous UTI that occurred in association with concurrent chemoradiotherapy for lung cancer. A variety of adverse events can occur during the course of chemoradiotherapy; serious infection represents one of the most critical adverse events. Emphysematous UTI is a rare form of bacterial infection that often causes sepsis and sometimes results in death. Emphysematous pyelonephritis is associated with a mortality rate of approximately 10–25% [1, 2, 3, 4]. The pathogenesis of emphysematous UTI is believed to be as follows: the infecting pathogen induces the fermentation of high concentrations of glucose and produces carbon dioxide [5]. DM is a major risk factor for this life-threatening disease [6]. A systematic review showed that DM was the most common underlying disease in patients with emphysematous pyelonephritis (96%), and that urinary tract obstruction was seen in 29% patients [1]. Our patient had 2 risk factors: DM and left megaureter of unknown cause. We suspect that chemoradiotherapy caused the development of emphysematous UTI in the present case. More than 60% of patients receiving concurrent chemoradiotherapy develop grade ≥3 neutropenia, and 0–23% develop infection (based on the Common Terminology Criteria for Adverse Events version 3.0 or later) [7, 8, 9]. In the present case, the patient's WBC count was within normal limits despite the serious infection, which indicated the existence of bone marrow suppression by chemoradiotherapy. Bone marrow suppression is thought to be a factor that influences the development of emphysematous UTI.\n\nThe weekly administration of dexamethasone during chemoradiotherapy can give rise to the development of emphysematous UTI due to worsening diabetes control. Although the patient's creatinine level was normal, she had a single kidney. Thus, we selected a weekly carboplatin-based chemotherapy regimen. Carboplatin is less nephrotoxic than cisplatin and is administered with adjustment for the patient's renal function. A weekly carboplatin plus paclitaxel regimen with thoracic radiotherapy is generally selected for patients with locally advanced non-small-cell lung cancer. The weekly regimen was considered to have equivalent efficacy and to be less toxic than standard cisplatin-based regimens [8]. Dexamethasone is usually administered in chemotherapy for antiemesis. According to a recent guideline, the administration of dexamethasone (8 mg/day) for 3–4 days is recommended for patients receiving carboplatin-containing regimens [10]. However, the regular weekly administration of dexamethasone is expected to worsen diabetes control. Although our patient's hemoglobin A1c had actually increased to 8.8% at the time, the time to the onset of the patient's disease seemed to be short. We therefore suspect that dexamethasone-induced hyperglycemia, in addition to other risk factors, accelerated the development of emphysematous UTI. The administration interval of chemotherapeutic agents is generally longer in patients receiving cisplatin-containing regimens, which results in a lower dosage of dexamethasone being administered in comparison to carboplatin-containing regimens. Nonetheless, we still believe that the weekly regimen was the only acceptable regimen for the present patient, who had a single kidney.\n\nWe describe a case of emphysematous UTI associated with concurrent chemoradiotherapy for lung cancer. The weekly administration of dexamethasone during chemoradiotherapy can give rise to the development of emphysematous UTI as a result of worsening diabetes control. In addition, urinary tract obstruction and bone marrow suppression by chemoradiotherapy contributed to the disease development in the present case. Although emphysematous UTI associated with antineoplastic therapy is a rare condition, we should be alert for the development of serious infection and select optimal chemotherapy regimens for patients who have risk factors for infection.\n\nStatement of Ethics\nInformed consent was obtained from the patient's family for publication of this case report.\n\nDisclosure Statement\nThe authors declare no conflicts of interest in association with the present study.\n\nAcknowledgments\nWe thank Dr. Ichiro Kawahara and his colleagues (Department of Urology, Harasanshin Hospital, Fukuoka, Japan) for performing the urological evaluation and treatment.\n\nFig. 1 Contrast-enhanced computed tomography images showing the enlargement of the left kidney, renal pelvis, and ureter (a–c) and gas accumulation within the renal pelvis, ureter, and bladder (a–d). The patient's right kidney is absent, and a thickened gastric wall can be observed (arrows).\n==== Refs\nReferences\n1 Falagas ME Alexiou VG Giannopoulou KP Siempos II Risk factors for mortality in patients with emphysematous pyelonephritis: a meta-analysis. J Urol 2007 178 880 885 17631348 \n2 Somani BK Nabi G Thorpe P Hussey J Cook J N'Dow J ABACUS Research Group Is percutaneous drainage the new gold standard in the management of emphysematous pyelonephritis? Evidence from a systematic review. J Urol 2008 179 1844 1849 18353396 \n3 Lin YC Lin YC Lin HD Lin LY Risk factors of renal failure and severe complications in patients with emphysematous pyelonephritis – a single-center 15-year experience. Am J Med Sci 2012 343 186 191 21804369 \n4 Lu YC Chiang BJ Pong YH Huang KH Hsueh PR Huang CY Pu YS Predictors of failure of conservative treatment among patients with emphysematous pyelonephritis. BMC Infect Dis 2014 14 418 25074590 \n5 Yang WH Shen NC Gas-forming infection of the urinary tract: an investigation of fermentation as a mechanism. J Urol 1990 143 960 964 2184258 \n6 Pontin AR Barnes RD Joffe J Kahn D Emphysematous pyelonephritis in diabetic patients. Br J Urol 1995 75 71 74 7850302 \n7 Segawa Y Kiura K Takigawa N Kamei H Harita S Hiraki S Watanabe Y Sugimoto K Shibayama T Yonei T Ueoka H Takemoto M Kanazawa S Takata I Nogami N Hotta K Hiraki A Tabata M Matsuo K Tanimoto M Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer: OLCSG 0007. J Clin Oncol 2010 28 3299 3306 20530281 \n8 Yamamoto N Nakagawa K Nishimura Y Tsujino K Satouchi M Kudo S Hida T Kawahara M Takeda K Katakami N Sawa T Yokota S Seto T Imamura F Saka H Iwamoto Y Semba H Chiba Y Uejima H Fukuoka M Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol 2010 28 3739 3745 20625120 \n9 Sugawara S Maemondo M Tachihara M Inoue A Ishimoto O Sakakibara T Usui K Watanabe H Matsubara N Watanabe K Kanazawa K Ishida T Saijo Y Nukiwa T North Japan Lung Cancer Study Group Randomized phase II trial of uracil/tegafur and cisplatin versus vinorelbine and cisplatin with concurrent thoracic radiotherapy for locally advanced unresectable stage III non-small-cell lung cancer: NJLCG 0601. Lung Cancer 2013 81 91 96 23643176 \n10 Roila F Molassiotis A Herrstedt J Aapro M Gralla RJ Bruera E Clark-Snow RA Dupuis LL Einhorn LH Feyer P Hesketh PJ Jordan K Olver I Rapoport BL Roscoe J Ruhlmann CH Walsh D Warr D van der Wetering M participants of the MASCC/ESMO Consensus Conference Copenhagen 2015 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol 2016 27 v119 v133 27664248\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "1662-6575", "issue": "10(1)", "journal": "Case reports in oncology", "keywords": "Adverse event; Chemoradiotherapy; Emphysematous cystitis; Emphysematous pyelonephritis; Lung cancer", "medline_ta": "Case Rep Oncol", "mesh_terms": null, "nlm_unique_id": "101517601", "other_id": null, "pages": "239-243", "pmc": null, "pmid": "28638336", "pubdate": "2017", "publication_types": "D002363:Case Reports", "references": "25074590;23643176;21804369;17631348;7850302;18353396;20530281;27664248;2184258;20625120", "title": "Emphysematous Pyelonephritis and Cystitis: Unusual Adverse Events during Concurrent Chemoradiotherapy for Lung Cancer.", "title_normalized": "emphysematous pyelonephritis and cystitis unusual adverse events during concurrent chemoradiotherapy for lung cancer" }

[ { "companynumb": "JP-TEVA-786267ROM", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MG/ME2", "drugenddate": null, "drugenddateformat": null, "drugindication": "NON-SMALL CELL LUNG CANCER STAGE IIIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "77269", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "AREA UNDER CURVE 2", "drugenddate": null, "drugenddateformat": null, "drugindication": "NON-SMALL CELL LUNG CANCER STAGE IIIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "8 MG/DAY ON DAY 2 AND DAY 3; EVERY WEEK", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIEMETIC SUPPORTIVE CARE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG/DAY ON DAY 1", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIEMETIC SUPPORTIVE CARE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." } ], "patientagegroup": null, "patientonsetage": "67", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Urinary tract obstruction", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bone marrow failure", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diabetes mellitus inadequate control", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Emphysematous pyelonephritis", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Emphysematous cystitis", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Klebsiella infection", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "YOKOYAMA T, SHINOZAKI S, ARIMURA H, NAKATOMI K, WATAYA H. EMPHYSEMATOUS PYELONEPHRITIS AND CYSTITIS: UNUSUAL ADVERSE EVENTS DURING CONCURRENT CHEMORADIOTHERAPY FOR LUNG CANCER. CASE-REP-ONCOL 2017;10(1):239-243.", "literaturereference_normalized": "emphysematous pyelonephritis and cystitis unusual adverse events during concurrent chemoradiotherapy for lung cancer", "qualification": "1", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20170712", "receivedate": "20170712", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13746539, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20171127" }, { "companynumb": "PHHY2017JP098439", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "10 MG/DAY ON DAY 1", "drugenddate": null, "drugenddateformat": null, "drugindication": "PROPHYLAXIS OF NAUSEA AND VOMITING", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": "3", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "8 MG/DAY ON DAYS 2 AND 3", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "40 MG/M2, QW", "drugenddate": null, "drugenddateformat": null, "drugindication": "NON-SMALL CELL LUNG CANCER STAGE III", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "76959", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK UNK, QW", "drugenddate": null, "drugenddateformat": null, "drugindication": "NON-SMALL CELL LUNG CANCER STAGE III", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INSULIN NOS" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DIABETES MELLITUS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INSULIN" } ], "patientagegroup": null, "patientonsetage": "67", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pyrexia", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Emphysematous pyelonephritis", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Cystitis", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Klebsiella infection", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "YOKOYAMA T, SHINOZAKI S, ARIMURA H, NAKATOMI K, WATAYA H. EMPHYSEMATOUS PYELONEPHRITIS AND CYSTITIS: UNUSUAL ADVERSE EVENTS DURING CONCURRENT CHEMORADIOTHERAPY FOR LUNG CANCER. CASE REPORTS IN ONCOLOGY. 2017;10(1):239-243", "literaturereference_normalized": "emphysematous pyelonephritis and cystitis unusual adverse events during concurrent chemoradiotherapy for lung cancer", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20171227", "receivedate": "20170712", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13744350, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20180320" }, { "companynumb": "JP-FRESENIUS KABI-FK201706016", "fulfillexpeditecriteria": "1", "occurcountry": "JP", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "042", "drugauthorizationnumb": "084916", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "VOMITING", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "10", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE INJECTION (MANUFACTURER UNKNOWN)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "DEXAMETHASONE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "084916", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "8", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "DEXAMETHASONE INJECTION (MANUFACTURER UNKNOWN)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CARBOPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "077266", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NON-SMALL CELL LUNG CANCER STAGE IIIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CARBOPLATIN (MANUFACTURER UNKNOWN)" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PACLITAXEL" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "NON-SMALL CELL LUNG CANCER STAGE IIIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "40", "drugstructuredosageunit": "009", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PACLITAXEL." } ], "patientagegroup": null, "patientonsetage": "67", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Urinary tract infection", "reactionmeddraversionpt": "20.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "YOKOYAMA T,SHINOZAKI S,ARIMURA H,NAKATOMI K,WATAYA H. EMPHYSEMATOUS PYELONEPHRITIS AND CYSTITIS: UNUSUAL ADVERSE EVENTS DURING CONCURRENT CHEMORADIOTHERAPY FOR LUNG CANCER. CASE REP ONCOL 2017;10 (1):239-243.", "literaturereference_normalized": "emphysematous pyelonephritis and cystitis unusual adverse events during concurrent chemoradiotherapy for lung cancer", "qualification": "3", "reportercountry": "JP" }, "primarysourcecountry": "JP", "receiptdate": "20170713", "receivedate": "20170713", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13751661, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20171127" } ]

{ "abstract": "ST segment elevation is associated with non-cardiac pathologies but is not as well reported as myocardial infarction. We present a case of a 63-year-old man who was admitted for an overdose on cyclobenzaprine with signs of anti-cholinergic toxicity. He developed signs of ileus on imaging and became progressively obtunded. He was noted to have ST segment elevations on electrocardiogram (EKG) with no troponin elevation. Patient required urgent catheterization which showed normal coronary arteries. His bowel was decompressed subsequently resulting in resolution of the ST segment changes. Other cases of ST segment elevations with gastrointestinal pathologies including cholecystitis, pancreatitis and gastric dilation have been reported but the etiology is still unclear. This case illustrates the importance of understanding EKGs in the clinical context. ST segment elevation on EKG, if there is contradicting symptomology and lab reports, should be further investigated to prevent unnecessary work-up and potentially dangerous therapies. [Full article available at http://rimed.org/rimedicaljournal-2016-11.asp].", "affiliations": "Providence VA Medical Center, The Warren Alpert Medical School, Brown University.;Providence VA Medical Center, The Warren Alpert Medical School, Brown University.;Providence VA Medical Center, The Warren Alpert Medical School, Brown University.;Providence VA Medical Center, The Warren Alpert Medical School, Brown University.", "authors": "Siddique|Osama|O|;Rasla|Somwail|S|;Clark|Seth|S|;Kokkirala|Aravind|A|", "chemical_list": "D000929:Antidepressive Agents, Tricyclic; D014336:Troponin; D000639:Amitriptyline; C004704:cyclobenzaprine", "country": "United States", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0363-7913", "issue": "99(11)", "journal": "Rhode Island medical journal (2013)", "keywords": "Ileus; ST segment elevation; STEMI; non-cardiac", "medline_ta": "R I Med J (2013)", "mesh_terms": "D000639:Amitriptyline; D000929:Antidepressive Agents, Tricyclic; D002404:Catheterization; D004562:Electrocardiography; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072657:ST Elevation Myocardial Infarction; D014336:Troponin", "nlm_unique_id": "101605827", "other_id": null, "pages": "44-46", "pmc": null, "pmid": "27801921", "pubdate": "2016-11-01", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "A Case of Ileus and ST Segment Elevation.", "title_normalized": "a case of ileus and st segment elevation" }

[ { "companynumb": "US-STRIDES ARCOLAB LIMITED-2017SP006945", "fulfillexpeditecriteria": "2", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "78329", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MELOXICAM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MELOXICAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CYCLOBENZAPRINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, UNKNOWN", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOBENZAPRINE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Overdose", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SIDDIQUE O, RASLA S, CLARK S, KOKKIRALA A. A CASE OF ILEUS AND ST SEGMENT ELEVATION. R I MED J (2013). 2016?99(11):44-46", "literaturereference_normalized": "a case of ileus and st segment elevation", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20180222", "receivedate": "20180222", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14560734, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20180509" }, { "companynumb": "US-TEVA-768268USA", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "MELOXICAM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "77936", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "OVERDOSE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MELOXICAM." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "074978", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "OVERDOSE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYCLOBENZAPRINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "071611", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "OVERDOSE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOBENZAPRINE." } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Retching", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Delirium", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Disorientation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Mental disorder", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Constipation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Electrocardiogram ST segment elevation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Ileus", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Agitation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Overdose", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dyspnoea", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SIDDIQUE O, RASLA S, CLARK S, KOKKIRALA A. A CASE OF ILEUS AND ST SEGMENT ELEVATION. R-I-MED-J 2016;99(11):44-46.", "literaturereference_normalized": "a case of ileus and st segment elevation", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20170516", "receivedate": "20170516", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13551827, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20170830" }, { "companynumb": "US-MYLANLABS-2017M1027009", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYCLOBENZAPRINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "073144", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOBENZAPRINE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MELOXICAM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MELOXICAM." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Electrocardiogram ST segment elevation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Agitation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Ileus", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Delirium", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dyspnoea", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Mental disorder", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Overdose", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Disorientation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Diarrhoea", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Constipation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Retching", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SIDDIQUE O, RASLA S, CLARK S, KOKKIRALA A. A CASE OF ILEUS AND ST SEGMENT ELEVATION. R-I-MED-J 2016;99(11):44-46.", "literaturereference_normalized": "a case of ileus and st segment elevation", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20170508", "receivedate": "20170508", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13521897, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20170830" }, { "companynumb": "US-CIPLA LTD.-2016US21266", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "MELOXICAM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "077929", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MELOXICAM." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYCLOBENZAPRINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOBENZAPRINE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Ileus", "reactionmeddraversionpt": "22.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Electrocardiogram ST segment elevation", "reactionmeddraversionpt": "22.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Overdose", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SIDDIQUE O, RASLA S, CLARK S AND KOKKIRALA A. A CASE OF ILEUS AND ST SEGMENT ELEVATION. RHODE ISLAND MEDICAL JOURNAL. 2016?99 (11):44 TO 46", "literaturereference_normalized": "a case of ileus and st segment elevation", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190923", "receivedate": "20161122", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 12963177, "safetyreportversion": 5, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20191004" }, { "companynumb": "US-OXFORD PHARMACEUTICALS, LLC-2018OXF00060", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOBENZAPRINE HYDROCHLORIDE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "077209", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOBENZAPRINE HYDROCHLORIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MELOXICAM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MELOXICAM." } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Overdose", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Electrocardiogram ST segment elevation", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Delirium", "reactionmeddraversionpt": "21.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Ileus", "reactionmeddraversionpt": "21.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dyspnoea", "reactionmeddraversionpt": "21.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SIDDIQUE O, RASLA S, CLARK S, KOKKIRALA A. A CASE OF ILEUS AND ST SEGMENT ELEVATION. R I MED J. 2016?99(11):44-46", "literaturereference_normalized": "a case of ileus and st segment elevation", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20180605", "receivedate": "20180605", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 14974560, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180711" }, { "companynumb": "US-ZYDUS-015214", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOBENZAPRINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOBENZAPRINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MELOXICAM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "077921", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MELOXICAM." } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Condition aggravated", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Nausea", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Retching", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Electrocardiogram ST segment elevation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Dyspnoea", "reactionmeddraversionpt": "20.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Agitation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Delirium", "reactionmeddraversionpt": "20.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Ileus", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Overdose", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Disorientation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Mental status changes", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Bowel movement irregularity", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Abdominal distension", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "SIDDIQUE O, RASLA S, CLARK S, KOKKIRALA A. A CASE OF ILEUS AND ST SEGMENT ELEVATION. R-I-MED-J 2016;99(11):44-46.", "literaturereference_normalized": "a case of ileus and st segment elevation", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20170517", "receivedate": "20170517", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13553210, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20170830" }, { "companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2017US-140055", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "MELOXICAM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MELOXICAM." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOBENZAPRINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "78722", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOBENZAPRINE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Ileus", "reactionmeddraversionpt": "20.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Electrocardiogram ST segment elevation", "reactionmeddraversionpt": "20.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Delirium", "reactionmeddraversionpt": "20.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "20.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Overdose", "reactionmeddraversionpt": "20.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "SIDDIQUE O, RASLA S, CLARK S, KOKKIRALA A. A CASE OF ILEUS AND ST SEGMENT ELEVATION. R I MED J. 2016;NOV;99(11):44-6", "literaturereference_normalized": "a case of ileus and st segment elevation", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20171216", "receivedate": "20170509", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13526365, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20180320" }, { "companynumb": "US-JUBILANT CADISTA PHARMACEUTICALS-2017JUB00158", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOBENZAPRINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "077563", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOBENZAPRINE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MELOXICAM" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MELOXICAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "IBUPROFEN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "IBUPROFEN." } ], "patientagegroup": null, "patientonsetage": "63", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Atrial fibrillation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Ileus", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Delirium", "reactionmeddraversionpt": "20.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Dyspnoea", "reactionmeddraversionpt": "20.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Toxicity to various agents", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Overdose", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Electrocardiogram ST segment elevation", "reactionmeddraversionpt": "20.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "OSAMA SIDDIQUE, MD. A CASE OF ILEUS AND ST SEGMENT ELEVATION. R I MED J. 2016;99:44-46", "literaturereference_normalized": "a case of ileus and st segment elevation", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20170525", "receivedate": "20170525", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13580663, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 1, "seriousnessother": 1, "transmissiondate": "20170830" } ]

{ "abstract": "Solid organ transplant recipients are at risk for infectious complications due to chronic immunosuppression. The outbreak of coronavirus disease 2019 (COVID-19) in the United States has raised growing concerns for the transplant patient population. We seek to add to the current limited literature on COVID-19 in transplant recipients by describing the clinical course of two kidney transplant recipients with SARS-CoV-2 infection monitored by both RT-PCR and serology. Through careful adjustment of their immunosuppression regimen, both patients had excellent recovery with intact graft function and development of anti-SARS-CoV-2 antibodies.", "affiliations": "Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.;Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.;Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.;Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.;Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.", "authors": "Wang|Aileen X|AX|https://orcid.org/0000-0002-1097-9270;Quintero Cardona|Orlando|O|;Ho|Dora Y|DY|;Busque|Stephan|S|https://orcid.org/0000-0003-1048-1621;Lenihan|Colin R|CR|", "chemical_list": "D007166:Immunosuppressive Agents", "country": "Denmark", "delete": false, "doi": "10.1111/tid.13423", "fulltext": null, "fulltext_license": null, "issn_linking": "1398-2273", "issue": "23(1)", "journal": "Transplant infectious disease : an official journal of the Transplantation Society", "keywords": "COVID-19; RT-PCR; SARS-CoV-2; antibodies; immunosuppression; seroconversion", "medline_ta": "Transpl Infect Dis", "mesh_terms": "D000368:Aged; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents; D016030:Kidney Transplantation; D008875:Middle Aged; D000086402:SARS-CoV-2; D000069078:Seroconversion; D066027:Transplant Recipients", "nlm_unique_id": "100883688", "other_id": null, "pages": "e13423", "pmc": null, "pmid": "32701196", "pubdate": "2021-02", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Influence of immunosuppression on seroconversion against SARS-CoV-2 in two kidney transplant recipients.", "title_normalized": "influence of immunosuppression on seroconversion against sars cov 2 in two kidney transplant recipients" }

[ { "companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2021R1-305145", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MILLIGRAM, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "201691", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROXYCHLOROQUINE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Drug ineffective", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Condition aggravated", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "WANG AX, QUINTERO CARDONA O, HO DY, BUSQUE S, LENIHAN CR. INFLUENCE OF IMMUNOSUPPRESSION ON SEROCONVERSION AGAINST SARS?COV?2 IN TWO KIDNEY TRANSPLANT RECIPIENTS. TRANSPL INFECT DIS. 2021?23(1):E13423 (1?5)", "literaturereference_normalized": "influence of immunosuppression on seroconversion against sars cov 2 in two kidney transplant recipients", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210726", "receivedate": "20210726", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19612464, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "US-TEVA-2021-US-1936446", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "080356", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLIC ACID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "65457", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROXYCHLOROQUINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZITHROMYCIN ANHYDROUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZITHROMYCIN ANHYDROUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LOSARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOSARTAN." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WANG AX, QUINTERO CARDONA O, HO DY, BUSQUE S, LENIHAN CR. INFLUENCE OF IMMUNOSUPPRESSION ON SEROCONVERSION AGAINST SARS?COV?2 IN TWO KIDNEY TRANSPLANT RECIPIENTS. TRANSPL?INFECT?DIS 2021?23(1):E13423.", "literaturereference_normalized": "influence of immunosuppression on seroconversion against sars cov 2 in two kidney transplant recipients", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210805", "receivedate": "20210729", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19634937, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" }, { "companynumb": "US-MYLANLABS-2021M1044197", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "090596", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZITHROMYCIN ANHYDROUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZITHROMYCIN ANHYDROUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "LOSARTAN" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "50 MILLIGRAM, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "PRODUCT USED FOR UNKNOWN INDICATION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "50", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "LOSARTAN." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROXYCHLOROQUINE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "CEFTRIAXONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CEFTRIAXONE." } ], "patientagegroup": "6", "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "COVID-19", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WANG AX, QUINTERO CARDONA O, HO DY, BUSQUE S, LENIHAN CR. INFLUENCE OF IMMUNOSUPPRESSION ON SEROCONVERSION AGAINST SARS?COV?2 IN TWO KIDNEY TRANSPLANT RECIPIENTS. TRANSPL?INFECT?DIS 2021?23(1):E13423.", "literaturereference_normalized": "influence of immunosuppression on seroconversion against sars cov 2 in two kidney transplant recipients", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210723", "receivedate": "20210723", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19602947, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" }, { "companynumb": "US-TEVA-2021-US-1936447", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "080356", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLIC ACID" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "65457", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE" }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VALGANCICLOVIR" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIVIRAL PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VALGANCICLOVIR." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROXYCHLOROQUINE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIFUNGAL PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TRIMETHOPRIM?SULFAMETHOXAZOLE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANTI?THYMOCYTE GLOBULIN" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "COVID-19 pneumonia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WANG AX, QUINTERO CARDONA O, HO DY, BUSQUE S, LENIHAN CR. INFLUENCE OF IMMUNOSUPPRESSION ON SEROCONVERSION AGAINST SARS?COV?2 IN TWO KIDNEY TRANSPLANT RECIPIENTS. TRANSPL?INFECT?DIS 2021?23(1):E13423.", "literaturereference_normalized": "influence of immunosuppression on seroconversion against sars cov 2 in two kidney transplant recipients", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210729", "receivedate": "20210729", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19634928, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" }, { "companynumb": "NVSC2020US222836", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "65379", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "65461", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "ADJUSTED TO A LOWER TARGET LEVEL OF 4?7 NG/ML,", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "65461", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "VALGANCICLOVIR" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIVIRAL PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VALGANCICLOVIR." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIFUNGAL PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "SULFAMETHOXAZOLE AND TRIMETHOPRIM" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "COVID-19 pneumonia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" }, { "reactionmeddrapt": "Delayed graft function", "reactionmeddraversionpt": "23.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "WANG XA, CARDONA OQ, HO DY, BUSQUE S, LENIHAN CR. INFLUENCE OF IMMUNOSUPPRESSION ON SEROCONVERSION AGAINST SARS?COV?2 IN TWO KIDNEY TRANSPLANT RECIPIENTS. TRANSPLANT INFECTIOUS DISEASE. 2020?1?5", "literaturereference_normalized": "influence of immunosuppression on seroconversion against sars cov 2 in two kidney transplant recipients", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20200813", "receivedate": "20200813", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18147436, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20201103" }, { "companynumb": "US-PFIZER INC-202101120711", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "103676", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CONCENTRATE FOR SOLUTION FOR INFUSION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANTILYMPHOCYTE IMMUNOGLOBULINS" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "103676", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "CONCENTRATE FOR SOLUTION FOR INFUSION", "drugdosagetext": "5 MG/KG", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANTILYMPHOCYTE IMMUNOGLOBULINS" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MG, DAILY", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK; (ADJUSTED TO A LOWER TARGET LEVEL OF 4?7 NG/ML)", "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "2", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "RENAL TRANSPLANT", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "COVID-19 pneumonia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "WANG, A.. INFLUENCE OF IMMUNOSUPPRESSION ON SEROCONVERSION AGAINST SARS?COV?2 IN TWO KIDNEY TRANSPLANT RECIPIENTS. TRANSPLANT INFECTIOUS DISEASE. 2021?23 (1):1?5", "literaturereference_normalized": "influence of immunosuppression on seroconversion against sars cov 2 in two kidney transplant recipients", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210907", "receivedate": "20210907", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19798761, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "US-MYLANLABS-2021M1044336", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "VALGANCICLOVIR" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIVIRAL PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "VALGANCICLOVIR." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "TACROLIMUS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "090596", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TACROLIMUS." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "PREDNISONE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISONE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "HYDROXYCHLOROQUINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "COVID-19 PNEUMONIA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROXYCHLOROQUINE" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "THYMOCYTE IMMUNE GLOBULIN NOS" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5 MILLIGRAM/KILOGRAM", "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ANTITHYMOCYTE IMMUNOGLOBULIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "SULFAMETHOXAZOLE\\TRIMETHOPRIM" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "ANTIFUNGAL PROPHYLAXIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "TRIMETHOPRIM SULFAMETHOXAZOLE" } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "COVID-19 pneumonia", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "WANG AX, QUINTERO CARDONA O, HO DY, BUSQUE S, LENIHAN CR. INFLUENCE OF IMMUNOSUPPRESSION ON SEROCONVERSION AGAINST SARS?COV?2 IN TWO KIDNEY TRANSPLANT RECIPIENTS. TRANSPL?INFECT?DIS 2021?23(1):E13423.", "literaturereference_normalized": "influence of immunosuppression on seroconversion against sars cov 2 in two kidney transplant recipients", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210723", "receivedate": "20210723", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19602961, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20211014" } ]

{ "abstract": "To assess the incidence and the risk factors for zoster in patients exposed to intravenous cyclophosphamide (CYC) for systemic vasculitis or systemic lupus erythematosus (SLE), as well as the protective effect of prophylaxis by valacyclovir (VCV).\n\n\n\nThis retrospective study included all adults treated by intravenous CYC for SLE or systemic vasculitis between 2011 and 2015 at Toulouse University Hospital, France. Zoster occurrence was recorded using medical chart review, laboratory data, and patient interviews. Univariate Cox models were computed to assess the risk factors for zoster and the protective effect of prophylaxis by VCV.\n\n\n\nThe cohort consisted of 110 patients (81 systemic vasculitis and 29 SLE). During a mean followup of 3.4 years after CYC initiation, 10 cases of zoster occurred, leading to an overall incidence of 27.9/1000 patient-years (95% CI 15.2-50.6); it was 59.4/1000 patients (95% CI 27.5-123.6) during the year after CYC initiation. Four patients experienced persistent postherpetic neuralgia. Probable risk factors were lymphopenia < 500/µl at CYC initiation (HR 5.11, 95% CI 0.94-27.93) and female sex (HR 4.36, 95% CI 0.51-37.31). The incidence was higher in patients with SLE (HR as compared with systemic vasculitis patients = 2.68, 95% CI 0.54-13.26). None of the 19 patients exposed to VCV during the followup developed zoster.\n\n\n\nThe incidence of zoster is high in systemic vasculitis and in patients with SLE exposed to intravenous CYC. CYC may favor postherpetic neuralgia. Prophylaxis by VCV should be considered, particularly in cases of lymphopenia < 500/µl at CYC initiation and during the year after.", "affiliations": "From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France.;From Service de Maladies Infectieuses et Tropicales; Département de Néphrologie et transplantation d'organes, et Centre de Référence Maladies Rénales Rares; Service de Médecine Interne; CIC 1436; Service de Rhumatologie et Médecine Interne; Service de Pneumologie; Service de Médecine Interne, Fédération Digestive; Département d'information médicale; Service de Virologie, CHU de Toulouse; UMR 1027, Inserm-Université de Paul Sabatier, Toulouse, France. moulis.g@chu-toulouse.fr.", "authors": "Garnier|Camille|C|;Ribes|David|D|;Chauveau|Dominique|D|;Huart|Antoine|A|;Pugnet|Grégory|G|;Adoue|Daniel|D|;Prevot|Grégoire|G|;Alric|Laurent|L|;Delobel|Pierre|P|;Derumeaux|Hélène|H|;Mengelle|Catherine|C|;Sailler|Laurent|L|;Moulis|Guillaume|G|0000-0001-9953-4640", "chemical_list": "D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide", "country": "Canada", "delete": false, "doi": "10.3899/jrheum.180310", "fulltext": null, "fulltext_license": null, "issn_linking": "0315-162X", "issue": "45(11)", "journal": "The Journal of rheumatology", "keywords": "ANCA-ASSOCIATED VASCULITIS; EPIDEMIOLOGY; HERPES ZOSTER; SYSTEMIC LUPUS ERYTHEMATOSUS; SYSTEMIC VASCULITIS; VALACYCLOVIR", "medline_ta": "J Rheumatol", "mesh_terms": "D000328:Adult; D000368:Aged; D000998:Antiviral Agents; D003520:Cyclophosphamide; D005260:Female; D006562:Herpes Zoster; D006801:Humans; D007166:Immunosuppressive Agents; D015994:Incidence; D008180:Lupus Erythematosus, Systemic; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D014657:Vasculitis; D055815:Young Adult", "nlm_unique_id": "7501984", "other_id": null, "pages": "1541-1548", "pmc": null, "pmid": "30008461", "pubdate": "2018-11", "publication_types": "D016428:Journal Article", "references": null, "title": "Zoster after Cyclophosphamide for Systemic Lupus Erythematosus or Vasculitis: Incidence, Risk Factors, and Effect of Antiviral Prophylaxis.", "title_normalized": "zoster after cyclophosphamide for systemic lupus erythematosus or vasculitis incidence risk factors and effect of antiviral prophylaxis" }

[ { "companynumb": "FR-MYLANLABS-2018M1093858", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": "3000", "drugcumulativedosageunit": "003", "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "SYSTEMIC LUPUS ERYTHEMATOSUS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "065520", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." } ], "patientagegroup": null, "patientonsetage": "75", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Varicella zoster virus infection", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Post herpetic neuralgia", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GARNIER C, RIBES D, CHAUVEAU D, HUART A, PUGNET G, ADOUE D, ET AL. ZOSTER AFTER CYCLOPHOSPHAMIDE FOR SYSTEMIC LUPUS ERYTHEMATOSUS OR VASCULITIS: INCIDENCE, RISK FACTORS, AND EFFECT OF ANTIVIRAL PROPHYLAXIS. J-RHEUMATOL 2018?45(11):1541-1548.", "literaturereference_normalized": "zoster after cyclophosphamide for systemic lupus erythematosus or vasculitis incidence risk factors and effect of antiviral prophylaxis", "qualification": "1", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20181221", "receivedate": "20181221", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15750414, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" }, { "companynumb": "FR-MYLANLABS-2018M1093929", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": null, "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": "4440", "drugcumulativedosageunit": "003", "drugdosageform": "INJECTION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "GRANULOMATOSIS WITH POLYANGIITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZATHIOPRINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "075568", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZATHIOPRINE." } ], "patientagegroup": null, "patientonsetage": "87", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Post herpetic neuralgia", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Varicella zoster virus infection", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "GARNIER C, RIBES D, CHAUVEAU D, HUART A, PUGNET G, ADOUE D, ET AL. ZOSTER AFTER CYCLOPHOSPHAMIDE FOR SYSTEMIC LUPUS ERYTHEMATOSUS OR VASCULITIS: INCIDENCE, RISK FACTORS, AND EFFECT OF ANTIVIRAL PROPHYLAXIS. J-RHEUMATOL 2018?45(11):1541-1548.", "literaturereference_normalized": "zoster after cyclophosphamide for systemic lupus erythematosus or vasculitis incidence risk factors and effect of antiviral prophylaxis", "qualification": "1", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20181226", "receivedate": "20181226", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 15761466, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190205" }, { "companynumb": "FR-NOVPHSZ-PHHY2018FR187199", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "50722", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Systemic lupus erythematosus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "50722", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Immunosuppressant drug therapy", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Infusion", "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Systemic lupus erythematosus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE" } ], "patientagegroup": null, "patientonsetage": "75", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Post herpetic neuralgia", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Herpes zoster", "reactionmeddraversionpt": "24.1", "reactionoutcome": "3" }, { "reactionmeddrapt": "Varicella zoster virus infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Garnier C, Ribes D, Chauveau D, Huart A, Pugnet G, Adoue D et al. Zoster after Cyclophosphamide for Systemic Lupus Erythematosus or Vasculitis: Incidence, Risk Factors, and Effect of Antiviral Prophylaxis.. JOURNAL OF RHEUMATOLOGY. 2018;45:1541-1548.", "literaturereference_normalized": "zoster after cyclophosphamide for systemic lupus erythematosus or vasculitis incidence risk factors and effect of antiviral prophylaxis", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220204", "receivedate": "20220204", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "3", "safetyreportid": 20427820, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" }, { "companynumb": "FR-ROCHE-2244433", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "MICROSCOPIC POLYANGIITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "050722", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "MICROSCOPIC POLYANGIITIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL." } ], "patientagegroup": null, "patientonsetage": "67", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Varicella zoster virus infection", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Off label use", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Herpes zoster", "reactionmeddraversionpt": "21.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Intentional product use issue", "reactionmeddraversionpt": "21.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "GARNIER C. ZOSTER AFTER CYCLOPHOSPHAMIDE FOR SYSTEMIC LUPUS ERYTHEMATOSUS OR VASCULITIS: INCIDENCE, RISK FACTORS, AND EFFECT OF ANTIVIRAL PROPHYLAXIS. JOURNAL OF RHEUMATOLOGY. 2018?45(11):1541-1548.", "literaturereference_normalized": "zoster after cyclophosphamide for systemic lupus erythematosus or vasculitis incidence risk factors and effect of antiviral prophylaxis", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20190125", "receivedate": "20190125", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15866620, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190417" }, { "companynumb": "PHHY2018FR187205", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": "041", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": "1000", "drugcumulativedosageunit": "003", "drugdosageform": null, "drugdosagetext": "1000 MG (INFUSION)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Systemic lupus erythematosus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "1000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "65379", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Systemic lupus erythematosus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "65379", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Immunosuppressant drug therapy", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL" } ], "patientagegroup": null, "patientonsetage": "26", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Herpes zoster", "reactionmeddraversionpt": "24.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Varicella zoster virus infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Product use in unapproved indication", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "Garnier C, Ribes D, Chauveau D, Huart A, Pugnet G, Adoue D et al.. Zoster after cyclophosphamide for systemic lupus erythematosus or vasculitis: incidence, risk factors, and effect of antiviral prophylaxis. JOURNAL OF RHEUMATOLOGY. 2018;45:1541-8", "literaturereference_normalized": "zoster after cyclophosphamide for systemic lupus erythematosus or vasculitis incidence risk factors and effect of antiviral prophylaxis", "qualification": "3", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220125", "receivedate": "20181217", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 15731571, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" }, { "companynumb": null, "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "MYCOPHENOLATE MOFETIL" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": "065416", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Immunosuppressant drug therapy", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MYCOPHENOLATE MOFETIL" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CYCLOPHOSPHAMIDE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Systemic lupus erythematosus", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CYCLOPHOSPHAMIDE" } ], "patientagegroup": null, "patientonsetage": "26", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Herpes zoster", "reactionmeddraversionpt": "24.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Varicella zoster virus infection", "reactionmeddraversionpt": "24.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "Garnier C, Ribes D, Chauveau D, Huart A, Pugnet G, Adoue D et al.. Zoster after cyclophosphamide for systemic lupus erythematosus or vasculitis: incidence, risk factors, and effect of antiviral prophylaxis. JOURNAL OF RHEUMATOLOGY. 2018;45:1541-8", "literaturereference_normalized": "zoster after cyclophosphamide for systemic lupus erythematosus or vasculitis incidence risk factors and effect of antiviral prophylaxis", "qualification": "1", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20220225", "receivedate": "20220225", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "2", "safetyreportid": 20516611, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" } ]

{ "abstract": "OBJECTIVE\nTo describe a case of serous retinopathy and associated photoreceptor atrophy after intravenous cisplatin therapy.\n\n\nMETHODS\nEvaluation was performed using electroretinogram, optical coherence tomography, fundus autofluorescence, and funduscopic examinations to assess the extent of retinal disease, toxicity, and eventual atrophy.\n\n\nRESULTS\nA 56 year-old man with metastatic small cell carcinoma with vision changes after initiation of cisplatin therapy. The patient developed loss of vision to 20/400. A serous retinopathy was found on spectral domain optical coherence tomography with associated outer retinal atrophy and subretinal fibrosis. He developed outer ellipsoid layer atrophy after discontinuation of cisplatin therapy. He had patchy hypoautofluorescent areas in his macula on fundus autofluorescence and decreased cone response and slowed b-wave on electroretinogram. The serous retinopathy resolved with discontinuation of cisplatin and the malignancy was further managed with etoposide without recurrence of subretinal serous fluid or further vision loss.\n\n\nCONCLUSIONS\nCommonly used to treat various solid tumors, cisplatin is not without significant neurologic, ocular, and retinal toxicities. Multimodal imaging may further the authors' understanding of toxicity and this case highlights the benefits of optical coherence tomography, especially with color vision deviation or visual acuity change.", "affiliations": "Department of Ophthalmology, Nassau University Medical Center, East Meadow, New York.;Department of Ophthalmology, Harkness Eye Institute, Columbia University College of Physicians and Surgeons, New York, New York.;Department of Ophthalmology, Harkness Eye Institute, Columbia University College of Physicians and Surgeons, New York, New York.", "authors": "Langevin|Spencer|S|;Chang|Jonathan S|JS|;Chang|Stanley|S|", "chemical_list": "D000970:Antineoplastic Agents; D002945:Cisplatin", "country": "United States", "delete": false, "doi": "10.1097/ICB.0000000000000573", "fulltext": null, "fulltext_license": null, "issn_linking": "1935-1089", "issue": "13(3)", "journal": "Retinal cases & brief reports", "keywords": null, "medline_ta": "Retin Cases Brief Rep", "mesh_terms": "D000970:Antineoplastic Agents; D056833:Central Serous Chorioretinopathy; D002945:Cisplatin; D006801:Humans; D008297:Male; D008875:Middle Aged", "nlm_unique_id": "101298744", "other_id": null, "pages": "211-214", "pmc": null, "pmid": "28333855", "pubdate": "2019", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "SEROUS RETINOPATHY ASSOCIATED WITH CISPLATIN TREATMENT.", "title_normalized": "serous retinopathy associated with cisplatin treatment" }

[ { "companynumb": "US-MYLANLABS-2019M1066420", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "091062", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "INJECTION", "drugdosagetext": "4 CYCLES TOTALLY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "149", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Subretinal fibrosis", "reactionmeddraversionpt": "22.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Serous retinal detachment", "reactionmeddraversionpt": "22.0", "reactionoutcome": "2" }, { "reactionmeddrapt": "Maculopathy", "reactionmeddraversionpt": "22.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Retinopathy", "reactionmeddraversionpt": "22.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Blindness", "reactionmeddraversionpt": "22.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Cataract nuclear", "reactionmeddraversionpt": "22.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Retinal degeneration", "reactionmeddraversionpt": "22.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LANGEVIN S, CHANG JS, CHANG S. SEROUS RETINOPATHY ASSOCIATED WITH CISPLATIN TREATMENT. RETIN-CASES-BRIEF-REP 2019?13(3):211-214.", "literaturereference_normalized": "serous retinopathy associated with cisplatin treatment", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190715", "receivedate": "20190715", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16573777, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20191004" }, { "companynumb": "US-HQ SPECIALTY-US-2019INT000172", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, TWO ADDITIONAL CYCLES", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, 2 CYCLES", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "018057", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "149 MG, 2 CYCLES", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." }, { "actiondrug": "4", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, TWO ADDITIONAL CYCLES", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "018057", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, TWO ADDITIONAL CYCLES", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Blindness", "reactionmeddraversionpt": "22.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Retinopathy", "reactionmeddraversionpt": "22.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Maculopathy", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Retinal degeneration", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "LANGEVIN S, CHANG JS, CHANG S.. SEROUS RETINOPATHY ASSOCIATED WITH CISPLATIN TREATMENT.. RETIN CASES BRIEF REP.. 2019?13(3):211-214", "literaturereference_normalized": "serous retinopathy associated with cisplatin treatment", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190722", "receivedate": "20190722", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16611948, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20191004" }, { "companynumb": "US-ACCORD-049949", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "6 CYCLE", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "206774", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "2 CYCLES OF CISPLATIN (149 MG)", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "149", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Retinal degeneration", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Retinopathy", "reactionmeddraversionpt": "22.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Blindness", "reactionmeddraversionpt": "22.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Subretinal fibrosis", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Maculopathy", "reactionmeddraversionpt": "22.0", "reactionoutcome": "3" } ], "summary": null }, "primarysource": { "literaturereference": "LANGEVIN S, CHANG JS, CHANG S. SEROUS RETINOPATHY ASSOCIATED WITH CISPLATIN TREATMENT. RETIN CASES BRIEF REP. 2017 MAR 22.", "literaturereference_normalized": "serous retinopathy associated with cisplatin treatment", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190717", "receivedate": "20170407", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 13419692, "safetyreportversion": 3, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": 1, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20191004" }, { "companynumb": "US-TEVA-2019-US-1081421", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "6", "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": "2", "drugadministrationroute": "042", "drugauthorizationnumb": "74656", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "4 CYCLES TOTALLY", "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "149", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Maculopathy", "reactionmeddraversionpt": "22.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Chorioretinopathy", "reactionmeddraversionpt": "22.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Cataract nuclear", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Retinal degeneration", "reactionmeddraversionpt": "22.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Serous retinal detachment", "reactionmeddraversionpt": "22.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Subretinal fibrosis", "reactionmeddraversionpt": "22.0", "reactionoutcome": "3" }, { "reactionmeddrapt": "Blindness", "reactionmeddraversionpt": "22.0", "reactionoutcome": "3" } ], "summary": null }, "primarysource": { "literaturereference": "LANGEVIN S, CHANG JS, CHANG S. SEROUS RETINOPATHY ASSOCIATED WITH CISPLATIN TREATMENT. RETIN-CASES-BRIEF-REP 2019?13(3):211-214.", "literaturereference_normalized": "serous retinopathy associated with cisplatin treatment", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190723", "receivedate": "20190723", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16619122, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20191004" }, { "companynumb": "US-FRESENIUS KABI-FK201907979", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": "1", "drugadministrationroute": "042", "drugauthorizationnumb": "074735", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "SMALL CELL CARCINOMA", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "149", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN (MANUFACTURER UNKNOWN)" } ], "patientagegroup": null, "patientonsetage": "56", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Retinopathy", "reactionmeddraversionpt": "22.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "LANGEVIN S, CHANG J, CHANG S. SEROUS RETINOPATHY ASSOCIATED WITH CISPLATIN TREATMENT.. RETINAL CASES AND BRIEF REPORTS. 2019?211-214.", "literaturereference_normalized": "serous retinopathy associated with cisplatin treatment", "qualification": "3", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190718", "receivedate": "20190718", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16594901, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20191004" } ]

{ "abstract": "We present a case of a 16-year-old boy with Klinefelter syndrome who presented with a syndrome of impaired alertness, orofacial dyskinesias, choreiform movements, epileptic seizures, and autonomic instability, pointing to a diagnosis of anti-N-methyl-Daspartate (anti-NMDA) receptor antibody encephalitis.", "affiliations": "1Department of Neurology, Ghent University Hospital, Ghent, Belgium.", "authors": "Sommeling|Charlotte|C|;Santens|Patrick|P|", "chemical_list": "D000305:Adrenal Cortex Hormones", "country": "United States", "delete": false, "doi": "10.1177/0883073813520499", "fulltext": null, "fulltext_license": null, "issn_linking": "0883-0738", "issue": "29(5)", "journal": "Journal of child neurology", "keywords": "Klinefelter syndrome; anti-N-methyl-D-aspartate receptor encephalitis; autoimmune; teratoma", "medline_ta": "J Child Neurol", "mesh_terms": "D000293:Adolescent; D000305:Adrenal Cortex Hormones; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis; D006801:Humans; D008297:Male; D008479:Mediastinal Neoplasms; D011859:Radiography; D013724:Teratoma; D015898:Tomography Scanners, X-Ray Computed", "nlm_unique_id": "8606714", "other_id": null, "pages": "688-90", "pmc": null, "pmid": "24563471", "pubdate": "2014-05", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": null, "title": "Anti-N-methyl-D-aspartate (anti-NMDA) receptor antibody encephalitis in a male adolescent with a large mediastinal teratoma.", "title_normalized": "anti n methyl d aspartate anti nmda receptor antibody encephalitis in a male adolescent with a large mediastinal teratoma" }

[ { "companynumb": "BE-UCBSA-2014000842", "fulfillexpeditecriteria": "1", "occurcountry": "BE", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHYLPHENIDATE HYDROCHLORIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "021259", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "ATTENTION DEFICIT/HYPERACTIVITY DISORDER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHYLPHENIDATE HYDROCHLORIDE." } ], "patientagegroup": null, "patientonsetage": "16", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Teratoma", "reactionmeddraversionpt": "18.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Encephalitis autoimmune", "reactionmeddraversionpt": "18.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "SOMMELING C, SANTENS P. ANTI-N-METHYL-D-ASPARTATE (ANTI-NMDA) RECEPTOR ANTIBODY ENCEPHALITIS IN A MALE ADOLESCENT WITH A LARGE MEDIASTINAL TERATOMA. J CHILD NEUROL. 2014;29:688-90", "literaturereference_normalized": "anti n methyl d aspartate anti nmda receptor antibody encephalitis in a male adolescent with a large mediastinal teratoma", "qualification": "1", "reportercountry": "BE" }, "primarysourcecountry": "BE", "receiptdate": "20141020", "receivedate": "20140612", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10234053, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150528" } ]

{ "abstract": "Ovarian carcinosarcoma is also referred to as malignant mixed Mullerian tumor (MMMT). It is a rare neoplasm, and although it represents less than 5% of malignant ovarian tumors, it remains generally well-known among clinicians and pathologists. Rarer yet is ovarian teratoid carcinosarcoma, defined as carcinosarcoma with the added feature of immature neuroectodermal tissue, with or without elements of primitive germ cell tumor. To our knowledge, six ovarian teratoid carcinosarcomas have been reported in the literature [Matsuura et al. J Obstet Gynaecol Res. 2010 Aug; 36(4): 907-11]. These tumors resemble nasopharyngeal tumors of the same name. We report a 55-year-old woman seen at Orlando Health's division of gynecological oncology whose pathology showed ovarian teratoid carcinosarcoma, and present what we believe to be a seventh report of this entity.", "affiliations": "Obstetrics and Gynecology Residency Program, Orlando Health Department of Obstetrics and Gynecology, Orlando, Florida, USA.;Pathology Residency Program, Orlando Health Department of Pathology, Orlando, Florida, USA.;Orlando Health Department of Obstetrics and Gynecology, Division of Gynecological Oncology, Orlando, Florida, USA.;Orlando Health Department of Pathology, Orlando, Florida, USA.", "authors": "Fox|Courtney|C|;Allen|Nichole|N|;Schimp|Veronica|V|;Maksem|John|J|", "chemical_list": null, "country": "Switzerland", "delete": false, "doi": "10.1159/000498918", "fulltext": "\n==== Front\nCase Rep OncolCase Rep OncolCROCase Reports in Oncology1662-6575S. Karger AG Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.ch 10.1159/000498918cro-0012-0241Case ReportOvarian Teratoid Carcinosarcoma Is an Aggressive Tumor of Probable Mullerian Derivation with a Carcinosarcomatous and Mixed Germ-Cell Morphology Fox Courtney a*Allen Nichole bSchimp Veronica cMaksem John daObstetrics and Gynecology Residency Program, Orlando Health Department of Obstetrics and Gynecology, Orlando, Florida, USAbPathology Residency Program, Orlando Health Department of Pathology, Orlando, Florida, USAcOrlando Health Department of Obstetrics and Gynecology, Division of Gynecological Oncology, Orlando, Florida, USAdOrlando Health Department of Pathology, Orlando, Florida, USA*Courtney Fox, Orlando Health Department of Obstetrics and Gynecology, 1401 Lucerne Terrace, Orlando, FL 32806 (USA), E-Mail Courtney.fox@orlandohealth.comJan-Apr 2019 19 3 2019 19 3 2019 12 1 241 247 12 2 2019 13 2 2019 2019 Copyright © 2019 by S. Karger AG, Basel2019This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.Ovarian carcinosarcoma is also referred to as malignant mixed Mullerian tumor (MMMT). It is a rare neoplasm, and although it represents less than 5% of malignant ovarian tumors, it remains generally well-known among clinicians and pathologists. Rarer yet is ovarian teratoid carcinosarcoma, defined as carcinosarcoma with the added feature of immature neuroectodermal tissue, with or without elements of primitive germ cell tumor. To our knowledge, six ovarian teratoid carcinosarcomas have been reported in the literature [Matsuura et al. J Obstet Gynaecol Res. 2010 Aug; 36(4): 907–11]. These tumors resemble nasopharyngeal tumors of the same name. We report a 55-year-old woman seen at Orlando Health's division of gynecological oncology whose pathology showed ovarian teratoid carcinosarcoma, and present what we believe to be a seventh report of this entity.\n\nKey Words\nChemotherapyDrug TherapyGynecological CancerMolecular PathologyOvarian CarcinomaPathologyTargeted Therapy\n==== Body\nIntroduction\nTeratoid carcinosarcoma was first described in the nasopharynx [1] and ovarian teratoid carcinosarcoma, described in 1989 [2], closely resembles its nasopharyngeal counterpart. Teratoid carcinosarcomas are biologically aggressive tumors. All previously reported cases of ovarian teratoid carcinosarcoma occurred in post-menopausal women and were discovered in advanced clinical stages. As with their nasopharyngeal counterparts, all ovarian teratoid carcinosarcomas behaved in a highly aggressive manner [3]. Histologically, teratoid carcinosarcomas show an admixture of carcinosarcoma, primitive neural tissue (a component whose overall proportion has been associated with progressively worse prognosis in immature teratomas [4]), and other components of mixed germ cell tumor. Normally, mixed germ cell tumor of ovary is a tumor of children and young adults and is uncommon in postmenopausal women.\n\nCase Report\nA 55-year-old Caucasian woman presented to Orlando Health's gynecologic oncology division with complaints of increasing abdominal pain, low-grade fevers, and early satiety of approximately two months. Computed tomography showed ascites and a 13 cm in greatest dimension mixed cystic and solid mass in the central portion of her pelvis, without radiographic evidence of extra pelvic masses. Serum tumor markers were: increased quantitative HCG, 126 mIU/mL (reference range: ≤8 mIU/mL); increased α-1-Fetoprotein, 5.0 ng/mL (reference range: 0.0–0.9 ng/mL); increased Lactate Dehydrogenase, 406 U/L (reference range: 140–271 U/L); and increased CA-125, 599 U/mL (reference range: 0–35 U/mL). Following exploratory laparotomy, optimal tumor-reductive surgery was performed along with total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and omentectomy, leaving only microscopic residual disease.\n\nSurgical findings encompassed a 16.8 cm in greatest diameter left ovarian cystic, necrotic mass that had ruptured prior to surgery and in which there was pre-operative abdominal cavity spillage. The mass was uniformly soft, necrotic and approximately 50% attached to the cyst wall of the ovary. Pre-procedural pelvic washings were positive for malignant cells. Remaining surgical-pathology specimens were negative for malignancy; however, the opposite ovary showed clustered benign epithelial inclusions resembling a small adenofibroma that was WT1-negative, ER-positive and PAX8-positive and was consistent with endometrioid adenofibroma, generally considered a product of remote endometriosis. This observation is noteworthy, because the presentation of an aggressive tumor, for example clear cell carcinoma, as stage I disease is not an uncommon finding among endometriosis-associated malignancies; although, carcinosarcoma associated endometriosis is extremely rare [5].\n\nSpecimen microscopy showed assorted tumor components that comprised: (1) carcinosarcoma with EMA (epithelial membrane antigen) positive and PAX-8 positive glands that were present in a CD10 positive stroma; (2) immature teratoma with neuroepithelial, blastemal and primitive cartilage tissue; (3) immature embryonic elements including embryoid bodies that showed well-defined inner cell mass, trophoderm and yolk-sac; (4) an isolated focus resembling embryonal carcinoma; and, (5) an isolated focus of CD117 positive cells resembling dysgerminoma. Stage IC teratoid carcinosarcoma was diagnosed; and, an extramural expert consultant confirmed the diagnosis. Salient histopathological findings are highlighted in Figure 1.\n\nChemotherapeutic options were discussed with the patient; and proposed agents included carboplatin, paclitaxel and ifosfamide [6, 7, 8]. Also considered were bevacizumab and Herceptin. At the time of the first patient encounter, there were phase 1 and phase 2 randomized clinical trials for ovarian carcinosarcoma without extant phase 3 trials. The patient was made aware of the gravity of her disease and offered chemotherapy.\n\nThe patient elected to defer chemotherapy until disease recurrence. A month later, she presented with increasing abdominal girth, early satiety and abdominal discomfort. Computed tomography showed significant ascites, carcinomatosis, an 8 cm right pelvic sidewall mass, an abdominal wall nodule and an enlarged left internal iliac lymph node.\n\nShe underwent therapeutic paracentesis and chemotherapy port placement. Her initial chemotherapy included six cycles of ifosfamide and paclitaxel. She then received 3 cycles of carboplatin, gemzar (Gemcitabine, an antimetabolite used to treat a variety of cancers) and bevacizumab. Follow up computed tomography showed disease progression and chemotherapy was discontinued. She then received two cycles of nivolumab (Opdivo®, a PD-1 protein inhibitor used for platinum resistant tumors) but, again, showed disease progression. FoundationOne CDx TM Testing (Foundation Medicine, Cambridge, MA, USA; FDA approved as companion diagnostic in solid tumors, 2017) was performed on her tumor and the outcome revealed: PIK3CA E545K-subclonal, MSI-stable and Tumor Mutation Burden (TMB)–low, with 3 mutations per megabase. In this context, the Analysis of Tumor mutational burden (TMB) and Microsatellite Instability (MSI) serves as the basis for therapeutic decisions on cancer immunotherapies.\n\nBecause of the PIK3CA-E545K mutation, it was concluded that therapies that would potentially benefit this patient included the mTOR (mammalian target of rapamycin) inhibitors, Everolimus and Temsirolimus. The PIK3CA-E545K occurs within the highly conserved helical domain. Mutated PIK3CA proteins have increased catalytic activity resulting in enhanced downstream signaling and oncogenic transformation in vitro [9]. Alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway are common in endometrial cancers. PIK3CA mutations promote cell growth and invasion, are oncogenic both in vitro and in vivo, and have been associated with response to PI3K/AKT/mTOR signaling pathway inhibitors [9, 10, 11, 12].\n\nThe patient declined other chemotherapy or radiation therapy options and decided on going to University of Texas MD Anderson Cancer Center in Houston, Texas, USA, for further intervention. She was admitted to the hospital directly after her initial consultation. She was found to be in renal failure. She had bilateral percutaneous nephrostomy tubes placed and her renal function normalized. She was then given “BEP” as one 5-day cycle of Bleomycin, Etoposide, and Cisplatin [13]. She developed a neutropenic fever one week later, was hospitalized for another week, and died prior to being able to receive cycle 2. Her death occurred 14 months from the time of her initial surgery.\n\nDiscussion\nA malignant ovarian tumor composed of Mullerian epithelial tumor and malignant germ cell tumor is rare, with most cases composed of endometrioid adenocarcinoma and yolk sac tumor [14]. Ovarian carcinosarcoma with malignant neuroectodermal components resembling immature teratoma is extremely rare; and, to our knowledge, this is the seventh case of ovarian teratoid carcinosarcoma to be reported in the literature. It is uncertain whether this and other tumors of similar kind develop from arrested primitive embryonic tissues or from somatically derived pluripotential cells arising in the course of epithelial tumor dedifferentiation or in the course of epithelial to mesenchymal transition with the acquisition cellular stemness.\n\nTeratoid carcinosarcomas show significant tumor heterogeneity; and, we argue that, in this case, tumor heterogeneity is linked to carcinoma dedifferentiation followed by stable epithelial to mesenchymal transition (i.e., carcinosarcoma) with increased stemness leading to fetal-like stem cell emergence and the appearance of differentiated germ tumor end-products. Cellular differentiation is a process eventuating in cellular change, generally to a more specialized type. Ontogenetic differentiation happens when a multicellular organism changes from a simple zygote, for example, an embryo or embryoid body to a complex system of tissues and cell types. Cellular differentiation does not involve a change in the cells' DNA sequence. Tissue stem cells are a self-renewing population of cells that undergo divisions to self-renew or differentiate into multiple kinds of differentiated progeny. Stem cells have prolonged self-renewal ability, can repopulate the bone marrow in transplant paradigms, and can produce multiple phenotypes in colony assays [15, 16, 17].\n\nIt has become apparent that cancers are not composed of a group of near-homogenous, ectopically growing cells. Rather, cancer cells are heterogeneous, including in terms of their malignant potential to metastasize and to cause relapse. Phenotypic and functional heterogeneity arises among cancer cells within the same tumor because of genetic change, micro-environmental differences and reversible changes in cell properties. Cancers may contain a hierarchy of cells in which tumorigenic cancer stem cells may even differentiate into non-tumorigenic end-organ progeny [18]. Intra-tumor heterogeneity impedes the investigation and treatment of cancer since individual tumor-tissue samples may not be representative of the whole tumor. Cancer stem cells are the only cells within a tumor that possess indefinite self-renewal abilities and whose differentiation leads to the emergence of all cell types in the tumor [19, 20, 21, 22, 23].\n\nEpithelial to mesenchymal transitions (EMT) are transdifferentiation programs required for tissue morphogenesis during embryonic development (ontogenesis) and these programs reemerge during tissue repair and in tissue neoplasms. The EMT process is regulated by a diverse array of cytokines and growth factors that can be dysregulated during malignant tumor progression. EMT induction in cancer cells results in the acquisition of invasiveness, metastasis and drug resistance. Recent reports indicate that the emergence of stem cell-like features occurs as a result of EMT, for example, via cues from tumor stromal components [24]. Investigators from the Cancer Genome Atlas project identified a strong EMT gene signature in a subset of endometrial cancer cases that was attributable to epigenetic alterations at microRNA promoters; and, the range of EMT scores in uterine carcinosarcomas was the largest among all tumor types studied [25]. Dedifferentiation through aberrant activation of embryonic EMT enhances cancer cell motility and dissemination [26]; and, gene expression patterns in human cancers indicate that cancer cells combine EMT properties with a stem-cell phenotype that leads to cell migration and metastasis [27].\n\nTeratoid carcinosarcoma is a study in multipart tumor heterogeneity. Although it is uncertain whether this or other similar tumors develop from arrested primitive embryonic tissues or from somatically derived pluripotential cells arising in the course of epithelial tumor dedifferentiation or in the course of epithelial to mesenchymal transition, there is good data to favor a tumor's ability to eventuate in a complex, albeit disorganized, “organ system”. We speculate that this tumor may have arisen in the context of an endometriosis-associated malignancy, become a carcinosarcoma through EMT with stabilization of its stromal component and to have acquired stemness, also through EMT, allowing it to mimic the action of primitive stem cells and to exhibit multilineage differentiation. A Mullerian “endometrioid” underpinning of this lesion is proposed because: (1) there is morphological evidence of a contralateral endometriosis-associated benign lesion, (2) the tumor was confined to a large cyst of one ovary (stage I) – a typical finding of endometriosis associated neoplasms, (3) there was subclonal mutation of the PIK3CA-pathway – a common finding in endometriosis associated ovarian neoplasms, and (4) the carcinosarcoma's glands and stroma morphologically and immunohistochemically resembled those of homologous endometrial carcinosarcoma.\n\nThe EMT process and stemness may explain this tumor's ultimate resistance to any chemotherapy, as it appears that tumors presenting as heterogeneous tumor-tissue end products are highly resilient and can resist a variety of therapeutic assaults. Cancer metastasis and cancer drug resistance are two complex and poorly understood processes, which often co-exist clinically. EMT generates cancer stem cells that afford tumor heterogeneity and contributes to both metastasis and therapy resistance. EMT should be of therapeutic interest in the treatment of cancer and attempts should be made to target its pathways, either to prevent tumor dissemination in patients at high risk of developing metastatic lesions or to eradicate metastatic cancer cells in patients with advanced disease [28, 29, 30]. Being mindful of the above observations and recognizing the value of next generation sequence testing of tumor tissue could lead us to discover better treatment options with improved patient survival, especially for women with aggressive cancer subtypes.\n\nStatement of Ethics\nThe authors have no ethical conflicts to disclose.\n\nDisclosure Statement\nThe authors have no conflicts of interest to declare.\n\nFig. 1. A. Homologous carcinosarcoma with endometrioid gland morphology and nonspecific fibrous stroma. B. Primitive neuroepithelial tissue. C. CD117 positive cells (inset) resembling dysgerminoma. D. Embryoid body showing trophoderm, amniotic cavity, inner cell mass (ectoderm and endoderm), and yolk sac cavity. E. Primitive retinal tissue. F. Fetal cartilage.\n==== Refs\nReferences\n1 Shanmugaratnam K Kunaratnam N Chia KB Chiang GS Sinniah R Teratoid carcinosarcoma of the paranasal sinuses Pathology 1983 10 15 (4) 413 9 6674870 \n2 Gersell DJ Duncan DA Fulling KH Malignant mixed müllerian tumor of the uterus with neuroectodermal differentiation Int J Gynecol Pathol 1989 8 (2) 169 78 2541092 \n3 Matsuura Y Kitajima M Hachisuga T Tanimoto A Okura N Kihara I Malignant mixed müllerian tumor with malignant neuroectodermal components (teratoid carcinosarcoma) of the ovary: report of a case with clinicopathologic findings J Obstet Gynaecol Res 2010 8 36 (4) 907 11 20666968 \n4 Norris HJ Zirkin HJ Benson WL Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases Cancer 1976 5 37 (5) 2359 72 1260722 \n5 Amin K Brumley B Erickson BK Khalifa MA Müllerian carcinosarcoma arising from atypical pelvic endometriosis Gynecol Oncol Rep 2018 6 25 87 9 30014020 \n6 Homesley HD Filiaci V Markman M Bitterman P Eaton L Kilgore LC Gynecologic Oncology Group Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study J Clin Oncol 2007 2 25 (5) 526 31 17290061 \n7 Powell MA Filiaci VL Rose PG Mannel RS Hanjani P Degeest K Phase II evaluation of paclitaxel and carboplatin in the treatment of carcinosarcoma of the uterus: a Gynecologic Oncology Group study J Clin Oncol 2010 6 28 (16) 2727 31 20421537 \n8 Rauh-Hain JA Birrer M Del Carmen MG “Carcinosarcoma of the ovaryfallopian tubeand peritoneumprognostic factors and treatment modalities” Gynecol Oncol 2016 8 142 (2) 248 54 27321238 \n9 Kang S Bader AG Vogt PK Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic Proc Natl Acad Sci USA 2005 1 102 (3) 802 7 15647370 \n10 Bader AG Kang S Vogt PK Cancer-specific mutations in PIK3CA are oncogenic in vivo Proc Natl Acad Sci USA 2006 1 103 (5) 1475 9 16432179 \n11 Samuels Y Diaz LA Jr Schmidt-Kittler O Cummins JM Delong L Cheong I Mutant PIK3CA promotes cell growth and invasion of human cancer cells Cancer Cell 2005 6 7 (6) 561 73 15950905 \n12 Janku F Wheler JJ Naing A Falchook GS Hong DS Stepanek VM PIK3CA mutation H1047R is associated with response to PI3K/AKT/mTOR signaling pathway inhibitors in early-phase clinical trials Cancer Res 2013 1 73 (1) 276 84 23066039 \n13 Satoh T Aoki Y Kasamatsu T Ochiai K Takano M Watanabe Y Administration of standard-dose BEP regimen (bleomycin+etoposide+cisplatin) is essential for treatment of ovarian yolk sac tumour Eur J Cancer 2015 2 51 (3) 340 51 25559616 \n14 Roth LM Talerman A Levy T Sukmanov O Czernobilsky B Ovarian yolk sac tumors in older women arising from epithelial ovarian tumors or with no detectable epithelial component Int J Gynecol Pathol 2011 9 30 (5) 442 51 21804392 \n15 Lin H Schagat T Neuroblasts: a model for the asymmetric division of stem cells Trends Genet 1997 1 13 (1) 33 9 9009846 \n16 Morrison SJ Shah NM Anderson DJ Regulatory mechanisms in stem cell biology Cell 1997 2 88 (3) 287 98 9039255 \n17 Burns CE Zon LI Portrait of a stem cell Dev Cell 2002 11 3 (5) 612 3 12431368 \n18 Meacham CE Morrison SJ Tumour heterogeneity and cancer cell plasticity Nature 2013 9 501 (7467) 328 37 24048065 \n19 Reya T Morrison SJ Clarke MF Weissman IL Stem cellscancer, and cancer stem cells Nature 2001 11 414 (6859) 105 11 11689955 \n20 Al-Hajj M Clarke MF Self-renewal and solid tumor stem cells Oncogene 2004 9 23 (43) 7274 82 15378087 \n21 Bjerkvig R Tysnes BB Aboody KS Najbauer J Terzis AJ Opinion: the origin of the cancer stem cell: current controversies and new insights Nat Rev Cancer 2005 11 5 (11) 899 904 16327766 \n22 Bapat SA Evolution of cancer stem cells Semin Cancer Biol 2007 6 17 (3) 204 13 16787749 \n23 Michor F Polyak K The origins and implications of intratumor heterogeneity Cancer Prev Res (Phila) 2010 11 3 (11) 1361 4 20959519 \n24 Singh A Settleman J EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer Oncogene 2010 8 29 (34) 4741 51 20531305 \n25 Cherniack AD Shen H Walter V Stewart C Murray BA Bowlby R Cancer Genome Atlas Research Network Integrated Molecular Characterization of Uterine Carcinosarcoma Cancer Cell 2017 3 31 (3) 411 23 28292439 \n26 Thiery JP Acloque H Huang RY Nieto MA Epithelial-mesenchymal transitions in development and disease Cell 2009 11 139 (5) 871 90 19945376 \n27 Brabletz T Jung A Spaderna S Hlubek F Kirchner T Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression Nat Rev Cancer 2005 9 5 (9) 744 9 16148886 \n28 Davis FM Stewart TA Thompson EW Monteith GR Targeting EMT in cancer: opportunities for pharmacological intervention Trends Pharmacol Sci 2014 9 35 (9) 479 88 25042456 \n29 Fischer KR Durrans A Lee S Sheng J Li F Wong ST Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance Nature 2015 11 527 (7579) 472 6 26560033 \n30 Zheng X Carstens JL Kim J Scheible M Kaye J Sugimoto H Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer Nature 2015 11 527 (7579) 525 30 26560028\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "1662-6575", "issue": "12(1)", "journal": "Case reports in oncology", "keywords": "Chemotherapy; Drug Therapy; Gynecological Cancer; Molecular Pathology; Ovarian Carcinoma; Pathology; Targeted Therapy", "medline_ta": "Case Rep Oncol", "mesh_terms": null, "nlm_unique_id": "101517601", "other_id": null, "pages": "241-247", "pmc": null, "pmid": "31011323", "pubdate": "2019", "publication_types": "D002363:Case Reports", "references": "11689955;12431368;1260722;15378087;15647370;15950905;16148886;16327766;16432179;16787749;17290061;19945376;20421537;20531305;20666968;20959519;21804392;23066039;24048065;25042456;2541092;25559616;26560028;26560033;27321238;28292439;30014020;6674870;9009846;9039255", "title": "Ovarian Teratoid Carcinosarcoma Is an Aggressive Tumor of Probable Mullerian Derivation with a Carcinosarcomatous and Mixed Germ-Cell Morphology.", "title_normalized": "ovarian teratoid carcinosarcoma is an aggressive tumor of probable mullerian derivation with a carcinosarcomatous and mixed germ cell morphology" }

[ { "companynumb": "US-HIKMA PHARMACEUTICALS USA INC.-US-H14001-19-03752", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "BLEOMYCIN SULFATE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "065042", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BLEOMYCIN" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "ETOPOSIDE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ETOPOSIDE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CISPLATIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "OVARIAN CANCER", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CISPLATIN." } ], "patientagegroup": null, "patientonsetage": "55", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Febrile neutropenia", "reactionmeddraversionpt": "22.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "FOX C, ALLEN N, SCHIMP V, MAKSEM J. OVARIAN TERATOID CARCINOSARCOMA IS AN AGGRESSIVE TUMOR OF PROBABLE MULLERIAN DERIVATION WITH A CARCINOSARCOMATOUS AND MIXED GERM-CELL MORPHOLOGY. CASE REPORTS IN ONCOLOGY? DOI: 10.1159/000498918. 2019?12:1:241-247.", "literaturereference_normalized": "ovarian teratoid carcinosarcoma is an aggressive tumor of probable mullerian derivation with a carcinosarcomatous and mixed germ cell morphology", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20190612", "receivedate": "20190612", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 16419227, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20190711" } ]

{ "abstract": "Cardiac amyloidosis is a manifestation of multisystem disorder. The condition is rare, difficult to diagnose and invariably fatal. We report 2 cases of amyloidosis associated with plasma cell dyscrasia. A high index of clinical suspicion, echocardiographic clues (ventricular thickening, diastolic dysfunction, biatrial enlargement) and elevated cardiac biomarkers led to the diagnosis. Early institution of amyloid specific treatment should be the aim. Cardiac treatment is supportive and results are often disappointing.", "affiliations": "Registrar, Department of Cardiology, Bombay Hospital Institute of Medical Sciences, New Marine Lines, Mumbai 400020, Maharashtra, India. Electronic address: cbmunjewar@yahoo.co.in.;Registrar, Department of Cardiology, Bombay Hospital Institute of Medical Sciences, New Marine Lines, Mumbai 400020, Maharashtra, India.;Professor and Head, Department of Cardiology, Bombay Hospital Institute of Medical Sciences, New Marine Lines, Mumbai 400020, Maharashtra, India.", "authors": "Munjewar|Chandrashekhar|C|;Agrawal|Rahul|R|;Sharma|Satyavan|S|", "chemical_list": "D015415:Biomarkers", "country": "India", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0019-4832", "issue": "66(4)", "journal": "Indian heart journal", "keywords": "Cardiac amyloidosis; Plasma cell dyscrasia; Waldenstrom's macroglobulinemia", "medline_ta": "Indian Heart J", "mesh_terms": "D000368:Aged; D000686:Amyloidosis; D015415:Biomarkers; D009202:Cardiomyopathies; D015897:Comorbidity; D003937:Diagnosis, Differential; D004562:Electrocardiography; D017809:Fatal Outcome; D006439:Hemodynamics; D006801:Humans; D008297:Male; D055815:Young Adult", "nlm_unique_id": "0374675", "other_id": null, "pages": "473-6", "pmc": null, "pmid": "25173210", "pubdate": "2014", "publication_types": "D002363:Case Reports; D016428:Journal Article", "references": "18036445;16186440;21074364;15365071;9290406;22988049;7438392;23130126", "title": "Cardiac amyloidosis: a report of two cases.", "title_normalized": "cardiac amyloidosis a report of two cases" }

[ { "companynumb": "IN-CELGENE-078-21880-14093213", "fulfillexpeditecriteria": "1", "occurcountry": "IN", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "LENALIDOMIDE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": "021880", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Capsules", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CARDIAC AMYLOIDOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "REVLIMID" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "MELPHALAN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "021880", "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CARDIAC AMYLOIDOSIS", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MELPHALAN" } ], "patientagegroup": null, "patientonsetage": "72", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Death", "reactionmeddraversionpt": "18.0", "reactionoutcome": "5" } ], "summary": null }, "primarysource": { "literaturereference": "MUNJEWAR C, AGRAWAL R, SHARMA S. CARDIAC AMYLOIDOSIS: A REPORT OF TWO CASES.. INDIAN HEART JOURNAL. 2014 AUG;473-476.", "literaturereference_normalized": "cardiac amyloidosis a report of two cases", "qualification": "3", "reportercountry": "IN" }, "primarysourcecountry": "IN", "receiptdate": "20141001", "receivedate": "20141001", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 10487508, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20150528" } ]

{ "abstract": "Restless legs syndrome (RLS) is one of the most common sleep disorders. The purpose of this paper is a case description of the patient suffering from RLS, concurrent with numerous clinical problems. In our patient, during long-term therapy with a dopamine agonist (ropinirole), the phenomenon of the augmentation, defined as an increase in the severity of the RLS symptoms, was observed. The quality of life of the patient was significantly deteriorated. Due to the augmentation of RLS symptoms the dopaminergic drug was gradually withdrawn, and the gabapentin as a second-line drug for the treatment of RLS was introduced. Because of the large increase of both insomnia and RLS symptoms during the reduction of ropinirole dose, clonazepam was temporarily introduced. In addition, in the neurological assessment of the distal parts of the lower limb sensory disturbances of vibration were found. The neurographic study confirmed axonal neuropathy of the sural nerves, which explained an incomplete response to dopaminergic medications. However, gabapentin treatment in the dose recommended in neuropathies was impossible due to bothersome side effects. Another important issue in the treatment of the patient were depressive symptoms and the fact that the majority of used antidepressants (mirtazapine, mianserin, tricyclic antidepressants) increase the severity of RLS. Among antidepressants recommended for the treatment of depression in patients with RLS (such as bupropion, moclobemide, reboxetine, tianeptine and agomelatine) only agomelatine exhibits promoting sleep properties. Because of the concomitant insomnia, this drug was applied in our patient.", "affiliations": "III Klinika Psychiatryczna IPiN w Warszawie.;I Klinika Psychiatryczna IPiN w Warszawie.;Zakład Neurofizjologii Klinicznej IPiN w Warszawie.;Zakład Neurofizjologii Klinicznej IPiN w Warszawie.;III Klinika Psychiatryczna IPiN w Warszawie.;Zakład Neurofizjologii Klinicznej IPiN w Warszawie.;III Klinika Psychiatryczna IPiN w Warszawie.", "authors": "Narowska|Dominika|D|;Bożek|Milena|M|;Krysiak|Katarzyna|K|;Antczak|Jakub|J|;Holka-Pokorska|Justyna|J|;Jernajczyk|Wojciech|W|;Wichniak|Adam|A|", "chemical_list": "D000927:Anticonvulsants; D018491:Dopamine Agonists", "country": "Poland", "delete": false, "doi": null, "fulltext": null, "fulltext_license": null, "issn_linking": "0033-2674", "issue": "49(5)", "journal": "Psychiatria polska", "keywords": "augmentation; depression; restless leg syndrome", "medline_ta": "Psychiatr Pol", "mesh_terms": "D000368:Aged; D000927:Anticonvulsants; D003863:Depression; D018491:Dopamine Agonists; D005260:Female; D006801:Humans; D012148:Restless Legs Syndrome", "nlm_unique_id": "0103314", "other_id": null, "pages": "921-30", "pmc": null, "pmid": "26688843", "pubdate": "2015", "publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review", "references": null, "title": "Frequent difficulties in the treatment of restless legs syndrome - case report and literature review.", "title_normalized": "frequent difficulties in the treatment of restless legs syndrome case report and literature review" }

[ { "companynumb": "PL-GLAXOSMITHKLINE-PL2015GSK162395", "fulfillexpeditecriteria": "1", "occurcountry": "PL", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "ROPINIROLE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "020658", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "5.5 MG, QD", "drugenddate": null, "drugenddateformat": null, "drugindication": "RESTLESS LEGS SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "5.5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ROPINIROLE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM." } ], "patientagegroup": null, "patientonsetage": "72", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pain in extremity", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Anxiety", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Restless legs syndrome", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Insomnia", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Hypoaesthesia", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Condition aggravated", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Oedema peripheral", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Dysstasia", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "NAROWSKA D., BOZEK M., KRYSIAK K., ANTCZAK J., POKORSKA J.H., JERNAJCZYK W ET AL. FREQUENT DIFFICULTIES IN THE TREATMENT OF RESTLESS LEGS SYNDROME - CASE REPORT AND LITERATURE REVIEW. PSYCHIATRIA POLSKA. 2015?49:5:921-930", "literaturereference_normalized": "frequent difficulties in the treatment of restless legs syndrome case report and literature review", "qualification": "1", "reportercountry": "PL" }, "primarysourcecountry": "PL", "receiptdate": "20151113", "receivedate": "20151113", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11735088, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160304" }, { "companynumb": "PL-ALKEM-001427", "fulfillexpeditecriteria": "1", "occurcountry": "PL", "patient": { "drug": [ { "actiondrug": "2", "activesubstance": { "activesubstancename": "GABAPENTIN" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": "090858", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "AT INCREASED DOSE", "drugenddate": null, "drugenddateformat": null, "drugindication": "RESTLESS LEGS SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "900", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GABAPENTIN." }, { "actiondrug": null, "activesubstance": null, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": ".5", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "ROPINIROLE/ROPINIROLE HYDROCHLORIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "CLONAZEPAM" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "CLONAZEPAM." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "AGOMELATINE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "25", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AGOMELATINE" } ], "patientagegroup": null, "patientonsetage": "72", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Balance disorder", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "19.0", "reactionoutcome": "6" } ], "summary": null }, "primarysource": { "literaturereference": "NAROWSKA D, BOZEK M, KRYSIAK K, ANTCZAK J, HOLKA-POKORSKA J, JERNAJCZYK W, ET AL. FREQUENT DIFFICULTIES IN THE TREATMENT OF RESTLESS LEGS SYNDROME - CASE REPORT AND LITERATURE REVIEW. PSYCHIATR POL. 2015?49(5):921-930.", "literaturereference_normalized": "frequent difficulties in the treatment of restless legs syndrome case report and literature review", "qualification": "3", "reportercountry": "PL" }, "primarysourcecountry": "PL", "receiptdate": "20160112", "receivedate": "20160112", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11909530, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160526" }, { "companynumb": "PL-MYLANLABS-2015M1047600", "fulfillexpeditecriteria": "1", "occurcountry": "PL", "patient": { "drug": [ { "actiondrug": "4", "activesubstance": { "activesubstancename": "GABAPENTIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "900 MG/DAY", "drugenddate": null, "drugenddateformat": null, "drugindication": "RESTLESS LEGS SYNDROME", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "GABAPENTIN." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MIANSERIN" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MIANSERIN" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "MIRTAZAPINE" }, "drugadditional": null, "drugadministrationroute": "065", "drugauthorizationnumb": "076122", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "DEPRESSION", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "MIRTAZAPINE." } ], "patientagegroup": null, "patientonsetage": null, "patientonsetageunit": null, "patientsex": null, "patientweight": null, "reaction": [ { "reactionmeddrapt": "Dizziness", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Condition aggravated", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Balance disorder", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" }, { "reactionmeddrapt": "Restless legs syndrome", "reactionmeddraversionpt": "18.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "NAROWSKA D, BOZEK M, KRYSIAK K, ANTCZAK J, POKORSKA JH, JERNAJCZYK W, ET AL. FREQUENT DIFFICULTIES IN THE TREATMENT OF RESTLESS LEGS SYNDROME - CASE REPORT AND LITERATURE REVIEW. . PSYCHIATR-POL 2015?49(5):921-930.", "literaturereference_normalized": "frequent difficulties in the treatment of restless legs syndrome case report and literature review", "qualification": "3", "reportercountry": "PL" }, "primarysourcecountry": "PL", "receiptdate": "20151230", "receivedate": "20151230", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 11880103, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20160305" } ]

{ "abstract": "Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract with relapsing and remitting episodes. Abscesses and fistulas are the most common presentations of anorectal Crohn's disease. Antibiotics and surgical incision and drainage have been successful in treating perianal disease. We present here a 48-year-old woman with known case of Crohn's disease who presented with massive swelling in the perianal region with severe throbbing pain and high-grade fever, 38.2°C; the surgeon noted a large perianal abscess near the anal verge with redness, hotness, and tenderness. One and a half months from perianal abscess surgery, culture sensitivity was done due to delayed wound healing and passage of greenish discharge, and it revealed highly resistant bacteria Proteus mirabilis, Escherichia coli, and Staphylococci. In conclusion, clinicians should be aware that abscess and fistula have a fair chance to develop in Crohn's disease patients who are using immunomodulating and immunosuppressant therapy. In abscess and fistula cases, surgery should be determined as soon as possible, and close clinical monitoring should be performed. We recommend routine screening for enteric fistula and culture sensitivity of any discharge prior to the initiation of any antibiotic. Appropriate intervention should then be undertaken.", "affiliations": "Pathology Department, Faculty of Medicine, Umm Al-Qurra University, Mecca, Saudi Arabia.;Fifth year medical student, Umm Al-Qurra University, Mecca, Saudi Arabia.;Fifth year medical student, Umm Al-Qurra University, Mecca, Saudi Arabia.;Fifth year medical student, Umm Al-Qurra University, Mecca, Saudi Arabia.;Fifth year medical student, Umm Al-Qurra University, Mecca, Saudi Arabia.", "authors": "Ali|Abeer S|AS|;Alhothali|Omar S|OS|;Hammoudah|Abdulrahman A|AA|;Kh Alsaede|Abdullah|A|;Alraddadi|Ayman A|AA|", "chemical_list": null, "country": "Switzerland", "delete": false, "doi": "10.1159/000515611", "fulltext": "\n==== Front\nCase Rep Gastroenterol\nCase Rep Gastroenterol\nCRG\nCase Reports in Gastroenterology\n1662-0631\nS. Karger AG Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH-4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com\n\n10.1159/000515611\ncrg-0015-0626\nSingle Case\nMultidrug Resistance and Flaring up of Manifestation in Fistulizing Crohn's Disease after Surgery on a Perianal Lesion\nAli Abeer S. a *\nAlhothali Omar S. b\nHammoudah Abdulrahman A. b\nKh Alsaede Abdullah b\nAlraddadi Ayman A. b\naPathology Department, Faculty of Medicine, Umm Al-Qurra University, Mecca, Saudi Arabia\nbFifth year medical student, Umm Al-Qurra University, Mecca, Saudi Arabia\n*Abeer S. Ali, abeershaker72@gmail.com\nMay-Aug 2021\n8 7 2021\n8 7 2021\n15 2 626631\n10 2 2021\n19 2 2021\n2021\nCopyright © 2021 by S. Karger AG, Basel\n2021\nhttps://creativecommons.org/licenses/by-nc/4.0/ This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.\nCrohn's disease is a chronic inflammatory disease of the gastrointestinal tract with relapsing and remitting episodes. Abscesses and fistulas are the most common presentations of anorectal Crohn's disease. Antibiotics and surgical incision and drainage have been successful in treating perianal disease. We present here a 48-year-old woman with known case of Crohn's disease who presented with massive swelling in the perianal region with severe throbbing pain and high-grade fever, 38.2°C; the surgeon noted a large perianal abscess near the anal verge with redness, hotness, and tenderness. One and a half months from perianal abscess surgery, culture sensitivity was done due to delayed wound healing and passage of greenish discharge, and it revealed highly resistant bacteria Proteus mirabilis, Escherichia coli, and Staphylococci. In conclusion, clinicians should be aware that abscess and fistula have a fair chance to develop in Crohn's disease patients who are using immunomodulating and immunosuppressant therapy. In abscess and fistula cases, surgery should be determined as soon as possible, and close clinical monitoring should be performed. We recommend routine screening for enteric fistula and culture sensitivity of any discharge prior to the initiation of any antibiotic. Appropriate intervention should then be undertaken.\n\nKeywords\n\nCrohn's disease\nFistula\nMultidrug resistance\n==== Body\npmcIntroduction\n\nCrohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract with relapsing and remitting episodes, and it can affect the entire gastrointestinal tract. Clinical presentation of the disease includes right lower quadrant abdominal pain, chronic diarrhea, weight loss, fatigue, and anorexia. In approximately 50% of CD patients, extraintestinal manifestation may occur, such as pauciarticular large joint arthritis and erythema nodosum [1].\n\nSeveral perianal lesions including fissures, hemorrhoids, skin tags, fistulas and abscesses are associated with CD. These lesions can occur at any time in the course of the disease, and they occur in nearly half of the pediatric CD patients [2]. The most common presentations of anorectal CD are abscesses and fistulas. Twenty-six percent of patients will present with an abscess and an additional 29% will present with a fistula [3]. Treatment of the perianal abscess is surgery, but we can avoid emergent surgery by antibiotic and percutaneous drainage [1].\n\nAbout 66% of patients with inflammatory bowel disease (IBD) take corticosteroids, 14–20% are treated with immunomodulator therapy, and 5% use infliximab [4]. Around 15% of patients with IBD are treated with antibiotics over a period of 12 years. Patients with CD experience frequent hospitalizations and the routine use of antibiotics during their course of the disease, which may predispose them to antimicrobial-resistant microorganisms [5]. According to one study [6], there was no difference between IBD patients and non-IBD patients in the risk of antibiotic resistance except for high antibiotic exposure. We report a case of antimicrobial-resistant organisms and flaring up of manifestation after perianal abscess surgery in a long-standing CD female patient.\n\nCase Presentation\n\nHere, we report a case of a 48-year-old woman who was diagnosed with CD at the age of 41. Prior to the diagnosis, there were multiple surgical excisions of perianal skin tags which were diagnosed falsely as external hemorrhoids. Since the age of 41, the patient's drug therapy consisted of immunosuppressive infliximab intravenous injections and immunosuppressive azathioprine and mesalamine, an aminosalicylate anti-inflammatory agent. This aggressive drug therapy was prescribed in 2013 due to the first 2 entero-enteric fistulas. After healing of the fistulas after 6 months which was assessed through MRI for entero-enteric fistulas imaging, the treatment with anti-TNF antibodies continued and installed till now. The patient condition was not stable; on the last 7 years after 2 years from diagnosis, increasing trash level of infliximab occurred, and the gastroenterologist stopped infliximab for 2 months, and he recommended continuing immunosuppressive azathioprine and mesalamine with prednisolone 50 mg with gradual withdrawal of the dose and then subcutaneous adalimumab every 2 weeks. The condition was not improved; then, the patient was shifted to other monoclonal antibodies starting from certolizumab and vedolizumab and finally from December 2019 till now with ustekinumab (Stelara) and oral medications.\n\nIn December 2019, CT with contrast was performed as a routine follow-up, but the patient had severe anaphylactic reaction, and an aggressive course of oral corticosteroids was prescribed for 10 days. Missed diagnosis on reading the CT report. One week later after subsidence of anaphylactic reaction, a swelling in the perianal region with severe throbbing pain was felt and high-grade fever 38.2°C; the surgeon noted a large perianal abscess near the anal verge with redness, hotness, and tenderness. A course of Augmentin 1 g was prescribed with analgesic and antipyretics for 10 days; 2 days later from diagnosis, an opened sinus tract occurred discharging large amount of pus. In January 2020, MRI fistula was done which noted evidence of small right-sided intersphincteric horseshoe abscess 1.5 × 1 × 2.2 cm in intersphincteric space and extending from 7 to 9 o'clock continuous with right-sided low intersphincteric fistulous tract descending into the right side of the anal cleft. Fistulectomy operation was recommended, but due to unknown reason, the surgery was postponed till July 2020 where another MRI was done which was compared to previous imaging, and its opening was noted at 8 o'clock about 5.8 cm from the anal verge and descends at the intersphincteric space with small related horseshoe intersphincteric collection about 1.5 cm from the anal verge (shown in Fig. 1). Incision, excision of skin tags and fistulous tract which was sent to the pathologist, and drainage operation with antibiotics coverage were done, with recommendation to stop the immunomodulating therapy and immunosuppressant before and after the operation till complete healing and closure of the wound. Histopathology report revealed nonspecific inflammatory fistula showing granulation tissue lining consisting of newly formed small vascular channels, surrounded by fibroblastic proliferations with chronic inflammatory cellular infiltrations. The marginal surface epithelium shows acanthosis and hyperkeratosis with pseudoepitheliomatous hyperplasia (shown in Fig. 2a, b). One and a half months from operation, the surgeon prescribed culture sensitivity from the discharge, and it revealed highly resistant bacteria Proteus mirabilis and Escherichia coli (E. coli). Curam tablet (trimethoprim sulfamethoxazole) was prescribed for 14 days, but the condition was not improved. With the discharge passages, another culture sensitivity was done revealing P. mirabilis, E. coli, and Staphylococci. Antibiotic course was repeated with Flagyl 500 mg tablet, the opening closed after 4 months, and the patient was diagnosed with CD; fecal calprotectin 2000 μg/g, CRP 28 mg/L with abdominal distension, and passage of blood with defecation. The patient noted fecal incontinence, and the surgeon asked for MRI with contrast and examination of the fistulous tract under anesthesia to fulfill and evaluate the right diagnosis.\n\nDiscussion\n\nWe report a case of antimicrobial multidrug-resistant organisms and flaring up of manifestation after perianal abscess surgery in a patient with long-standing CD. Perianal abscesses are considered one of the most common surgical cases faced by both general and colorectal surgeons. Patients with perianal abscess present with severe pain, tenderness, swelling, and fluctuation on rectal examination. Extension of a cryptoglandular infection or obstruction of a perianal fistula is the main cause of perianal abscesses [3]. The management of perianal abscesses includes treatment of systemic symptoms with broad-spectrum antibiotics, but the definitive management is surgical incision and drainage [7] which has been delayed in our case.\n\nAntibiotics have been successful in treating perianal disease and have been used on the basis that the bacterial flora, especially anaerobes, contributes to perianal sepsis [7]. The routine use of antibiotics may be considered as malpractice and does not improve healing times in CD. Their use should be limited to treating patients with impaired resistance to infection such as immunosuppression, diabetes, and extensive cellulitis. A previous study showed resistance of Gram-negative bacteria to ciprofloxacin in CD patients with intra-abdominal abscesses [8]. In our case, one and a half months after perianal abscess surgery, culture sensitivity was done and revealed highly resistant bacteria P. mirabilis and E. coli and Staphylococci.\n\nImmunosuppressants such as corticosteroids and immunomodulators such as azathioprine are common therapies for patients with CD. Systemic corticosteroids have been widely used in CD remission induction. Immunomodulators are effective for remission maintenance, but not for remission induction [9]. They have not shown to be a risk factor for infectious complications following surgery. However, preoperative usage of CS is associated with postoperative infectious complications [10]. The presented case has been on multiple courses of CS which could be a cause of her development of postoperative wound infections.\n\nThe medical management of IBD has been revolutionized by TNF inhibitors, which include infliximab, adalimumab, golimumab, and certolizumab pegol. Anti-TNF agents inhibit disease activity and contribute to the healing of the mucosa. In the ACCENT II trial, which assessed infliximab as a maintenance therapy for fistulizing CD, 39% of patients in the infliximab maintenance arm had complete closure of all drainage fistulas, compared with only 9% in the placebo arm [9]. Ustekinumab is another biologic therapy approved for the treatment of mild to serious CD patients. It is a monoclonal antibody that blocks the common p40 subunit of IL-12 and IL-23 [11]. Our patient stopped using infliximab because she had increasing trash level of the drug and was on ustekinumab, and she stopped using it before and after the surgery to improve healing because no enough data support its effect in fistula remission. In a recent systemic review and meta-analysis of 27 controlled trials, a moderate-quality evidence was found to support the efficacy of ustekinumab to induce fistula remission, and more efficacy data are needed on this agent [11].\n\nFistulectomy is the excision of the complete fistula tract. It makes a larger wound compared to fistulotomy. This technique is usually used for intersphincteric or low transsphincteric perianal fistulae [12]. In our case, the patient had low intersphincteric fistulae and the surgeon decided to do fistulectomy, but the surgeon did not use Seton which can preserve the sphincter function, maybe because he anticipated that she will have fecal incontinence despite using Seton.\n\nIn conclusion, in CD patients who are using immunomodulating and immunosuppressant therapy, clinicians should be aware that abscess and fistula have a fair chance to develop. In cases in which abscess and fistula are suspected, surgery should be determined as soon as possible, and close clinical monitoring should be performed. We recommend routine screening for enteric fistula and culture sensitivity of any discharge prior to the initiation of any antibiotic. Appropriate intervention should then be undertaken.\n\nStatement of Ethics\n\nThis case report was approved by the Biomedical Ethics Committee. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.\n\nConflict of Interest Statement\n\nThe authors have no conflicts of interest to declare.\n\nFunding Sources\n\nThere was no financial support.\n\nAuthor Contributions\n\nAbeer Ali: corresponding author, manuscript writing, and literature review. Omar Alhothali: manuscript writing and literature review. Abdulrahman Hammoudah: manuscript writing and literature review. Abdullah Alsaede: manuscript review and literature review. Ayman Alraddadi: literature review and manuscript writing. All authors read and approved the final manuscript.\n\nFig. 1 MRI perianal fistula with small related horseshoe intersphincteric collection near the anal verge.\n\nFig. 2 a Nonspecific inflammatory fistula showing granulation tissue lining consisting of newly formed small vascular channels. b Acanthosis and hyperkeratosis with pseudoepitheliomatous hyperplasia. Power magnification for all microscopy images, ×10 objective and ×10 eyepiece.\n==== Refs\nReferences\n\n1 Torres J Mehandru S Colombel J-F Peyrin-Biroulet L Crohn's disease Lancet 2017 389 (10080) 1741 55 27914655\n2 Griffiths AM Specificities of inflammatory bowel disease in childhood Best Pract Res Clin Gastroenterol 2004 18 (3) 509 23 15157824\n3 Lewis RT Maron DJ Efficacy and complications of surgery for Crohn's disease Gastroenterol Hepatol 2010 6 (9) 587\n4 Hutfless SM Weng X Liu L Allison J Herrinton LJ Mortality by medication use among patients with inflammatory bowel disease, 1996–2003 Gastroenterology 2007 133 (6) 1779 86 18054550\n5 Epidemiological S Epidemiological and clinical features of Spanish patients with crohn's disease. Spanish epidemiological and economic study group on crohn's disease Eur J Gastroenterol Hepatol 1999 11 (10) 1121 7 10524641\n6 Leung W Malhi G Willey BM McGeer AJ Borgundvaag B Thanabalan R Prevalence and predictors of MRSA, ESBL, and VRE colonization in the ambulatory IBD population J Crohns Colitis 2012 6 (7) 743 9 22398097\n7 Singh B Jewell D George B Perianal Crohn's disease Br J Surg 2004 91 (7) 801 14 15227686\n8 Park SK Kim KJ Lee SO Yang DH Jung KW Ye BD Ciprofloxacin usage and bacterial resistance patterns in Crohn's disease patients with abscesses J Clin Gastroenterol 2014 48 (8) 703 7 24296421\n9 Gajendran M Loganathan P Catinella AP Hashash JG A comprehensive review and update on Crohn's disease Dis Mon 2018 64 (2) 20 57 28826742\n10 Aberra FN Lewis JD Hass D Rombeau JL Osborne B Lichtenstein GR Corticosteroids and immunomodulators: postoperative infectious complication risk in inflammatory bowel disease patients Gastroenterology 2003 125 (2) 320 7 12891531\n11 Lee MJ Parker CE Taylor SR Guizzetti L Feagan BG Lobo AJ Efficacy of medical therapies for fistulizing Crohn's disease: systematic review and meta-analysis Clin Gastroenterol Hepatol 2018 16 (12) 1879 92 29374617\n12 Keshaw H Foong KS Forbes A Day RM Perianal fistulae in Crohn's disease: current and future approaches to treatment Inflamm Bowel Dis 2010 16 (5) 870 80 19834976\n\n", "fulltext_license": "CC BY-NC", "issn_linking": "1662-0631", "issue": "15(2)", "journal": "Case reports in gastroenterology", "keywords": "Crohn's disease; Fistula; Multidrug resistance", "medline_ta": "Case Rep Gastroenterol", "mesh_terms": null, "nlm_unique_id": "101474819", "other_id": null, "pages": "626-631", "pmc": null, "pmid": "34616267", "pubdate": "2021", "publication_types": "D002363:Case Reports", "references": "18054550;24296421;15157824;22398097;10524641;27914655;29374617;12891531;15227686;28826742;21088749;19834976", "title": "Multidrug Resistance and Flaring up of Manifestation in Fistulizing Crohn's Disease after Surgery on a Perianal Lesion.", "title_normalized": "multidrug resistance and flaring up of manifestation in fistulizing crohn s disease after surgery on a perianal lesion" }

[ { "companynumb": "SA-MLMSERVICE-20211217-3279981-1", "fulfillexpeditecriteria": "1", "occurcountry": "SA", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "HYDROCORTISONE" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "8697", "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "100 MG", "drugenddate": null, "drugenddateformat": null, "drugindication": "Crohn^s disease", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "100", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "HYDROCORTISONE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "BUDESONIDE" }, "drugadditional": "2", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Capsule", "drugdosagetext": "3 DF, 1X/DAY (3 CAPSULE PER DAY FOR 4 WEEKS THEN GRADUAL WITHDRAWAL DURING THIS PERIOD)", "drugenddate": null, "drugenddateformat": null, "drugindication": "Crohn^s disease", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3", "drugstructuredosageunit": "032", "drugtreatmentduration": "4", "drugtreatmentdurationunit": "803", "medicinalproduct": "BUDESONIDE" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "BUDESONIDE" }, "drugadditional": "2", "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Capsule", "drugdosagetext": "UNK (3 CAPSULE PER DAY FOR 4 WEEKS THEN GRADUAL WITHDRAWAL DURING THIS PERIOD)", "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "BUDESONIDE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "USTEKINUMAB" }, "drugadditional": null, "drugadministrationroute": "058", "drugauthorizationnumb": null, "drugbatchnumb": "Unknown", "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK, MONTHLY", "drugenddate": null, "drugenddateformat": null, "drugindication": "Crohn^s disease", "drugintervaldosagedefinition": "802", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "201912", "drugstartdateformat": "610", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "STELARA" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "USTEKINUMAB" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Crohn^s disease", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "STELARA" } ], "patientagegroup": null, "patientonsetage": "48", "patientonsetageunit": "801", "patientsex": "2", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Vulvovaginal candidiasis", "reactionmeddraversionpt": "24.1", "reactionoutcome": "3" } ], "summary": null }, "primarysource": { "literaturereference": "Ali, A.. Multidrug resistance and flaring up of manifestation in fistulizing crohn^s disease after surgery on a perianal lesion. Case Reports in Gastroenterology. 2021;15 (2):626-631", "literaturereference_normalized": "multidrug resistance and flaring up of manifestation in fistulizing crohn s disease after surgery on a perianal lesion", "qualification": "3", "reportercountry": "SA" }, "primarysourcecountry": "SA", "receiptdate": "20220105", "receivedate": "20220105", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20299385, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" } ]

{ "abstract": "Several cases of Pneumocystosis pneumonia (PCP) have been reported in patients with hypercortisolism, mainly in patients with severe ectopic ACTH syndrome (EAS). We report 2 cases of PCP that did not develop until after starting treatment with metyrapone, one of which occurred in an outpatient with Cushing's disease (CD) without pulmonary symptoms before medical treatment for CD. Patient 1 presented as an outpatient with CD and severe hypercortisolism but nonetheless in good general condition. Treatment with metyrapone was started before pituitary surgery. Patient 2 had EAS due to prostate cancer. Respiratory failure in the two patients occurred 4 days and 30 days, respectively, after the start of metyrapone treatment. In both cases, chest CT showed bilateral interstitial infiltrates, and Pneumocystis jirovecii was found on bronchoalveolar lavage (BAL). A literature review was performed to identify risk factors for PCP in patients with CD: we identified 20 other cases of PCP in patients treated for hypercortisolism, including 16 patients with EAS. Ninety percent of patients had free urinary cortisol greater than 6 times the upper limit of normal (ULN). In conclusion, onset of PCP after initiation of anticortisolic therapy is not limited to patients with EAS, and may occur in CD patients with elevated cortisol levels, even if the patient remains in good general condition and has no pulmonary symptoms before treatment. In such patients, routine prophylactic treatment with trimethoprim/sulfamethoxazole (TMP/SMX) should be considered.", "affiliations": "Endocrinology Unit, University Hospital Centre Grenoble Alpes, CS 10217, 38043 Grenoble cedex 9, France. Electronic address: jcristante@chu-grenoble.fr.;Pharmacovigilance Unit, University Hospital Centre Grenoble Alpes, CS 10217, 38043 Grenoble cedex 9, France. Electronic address: mlepelley@chu-grenoble.fr.;Pharmacovigilance Unit, University Hospital Centre Grenoble Alpes, CS 10217, 38043 Grenoble cedex 9, France. Electronic address: mmallaret@chu-grenoble.fr.;Endocrinology Unit, Annecy Genevois Hospital Centre, 1, avenue de l'Hôpital, Epagny Metz-Tessy, BP 90074, 74374 Pringy Cedex, France. Electronic address: acarreau@ch-annecygenevois.fr.;Endocrinology Unit, University Hospital Centre Grenoble Alpes, CS 10217, 38043 Grenoble cedex 9, France. Electronic address: olivier.chabre@chu-grenoble.fr.", "authors": "Cristante|Justine|J|;Lepelley|Marion|M|;Mallaret|Michel|M|;Carreau|Agnès|A|;Chabre|Olivier|O|", "chemical_list": "D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D008797:Metyrapone", "country": "France", "delete": false, "doi": "10.1016/j.ando.2020.11.002", "fulltext": null, "fulltext_license": null, "issn_linking": "0003-4266", "issue": "81(6)", "journal": "Annales d'endocrinologie", "keywords": "Cushing's syndrome; Metyrapone; Métyrapone; Pneumocystosis; Pneumonie à pneumocystis; Syndrome de Cushing", "medline_ta": "Ann Endocrinol (Paris)", "mesh_terms": "D000182:ACTH Syndrome, Ectopic; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003480:Cushing Syndrome; D006801:Humans; D007153:Immunologic Deficiency Syndromes; D008297:Male; D008797:Metyrapone; D008875:Middle Aged; D009894:Opportunistic Infections; D010045:Outpatients; D011020:Pneumonia, Pneumocystis; D011292:Premedication; D012189:Retrospective Studies; D015662:Trimethoprim, Sulfamethoxazole Drug Combination", "nlm_unique_id": "0116744", "other_id": null, "pages": "551-560", "pmc": null, "pmid": "33278378", "pubdate": "2020-12", "publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review", "references": null, "title": "Pneumocystis pneumonia can complicate medical treatment of hypercortisolism even in outpatients with Cushing's disease.", "title_normalized": "pneumocystis pneumonia can complicate medical treatment of hypercortisolism even in outpatients with cushing s disease" }

[ { "companynumb": "FR-HRAPH01-202000927", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "METYRAPONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNK", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "PITUITARY-DEPENDENT CUSHING^S SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "201712", "drugstartdateformat": "610", "drugstructuredosagenumb": "3000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METYRAPONE" } ], "patientagegroup": null, "patientonsetage": "39", "patientonsetageunit": "801", "patientsex": "2", "patientweight": "105", "reaction": [ { "reactionmeddrapt": "Pneumocystis jirovecii pneumonia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 201712" } }, "primarysource": { "literaturereference": "CRISTANTE J, LEPELLEY M, MALLARET M, CARREAU A ET CHABRE O. PNEUMOCYSTIS PNEUMONIA CAN COMPLICATE MEDICAL TREATMENT OF HYPERCORTISOLISM EVEN IN OUTPATIENTS WITH CUSHING^S DISEASE. 8. ANN ENDOCRINOL (PARIS). 2020 DEC 02: S0003?4266(20)31302?0. DOI: 10.1016/J.ANDO.2020.11.002.", "literaturereference_normalized": "pneumocystis pneumonia can complicate medical treatment of hypercortisolism even in outpatients with cushing s disease", "qualification": "1", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20210106", "receivedate": "20210105", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18698234, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210419" }, { "companynumb": "FR-HRAPH01-202000928", "fulfillexpeditecriteria": "1", "occurcountry": "FR", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "METYRAPONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNK", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CUSHING^S SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": "2015", "drugstartdateformat": "602", "drugstructuredosagenumb": "750", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METYRAPONE" }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METYRAPONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": "UNK", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "GRADUALLY INCREASED UP TO 3000 MG PER DAY OVER A MONTH", "drugenddate": null, "drugenddateformat": null, "drugindication": "CUSHING^S SYNDROME", "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": "3000", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METYRAPONE" } ], "patientagegroup": null, "patientonsetage": "82", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pneumonia cytomegaloviral", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" }, { "reactionmeddrapt": "Pneumocystis jirovecii pneumonia", "reactionmeddraversionpt": "23.1", "reactionoutcome": "5" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 2015" } }, "primarysource": { "literaturereference": "CRISTANTE J, LEPELLEY M, MALLARET M, CARREAU A ET CHABRE O. PNEUMOCYSTIS PNEUMONIA CAN COMPLICATE MEDICAL TREATMENT OF HYPERCORTISOLISM EVEN IN OUTPATIENTS WITH CUSHING^S DISEASE. 8. ANN ENDOCRINOL (PARIS). 2020 DEC 02: S0003?4266(20)31302?0. DOI: 10.1016/J.ANDO.2020.11.002.", "literaturereference_normalized": "pneumocystis pneumonia can complicate medical treatment of hypercortisolism even in outpatients with cushing s disease", "qualification": "1", "reportercountry": "FR" }, "primarysourcecountry": "FR", "receiptdate": "20210108", "receivedate": "20210108", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18715214, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": 1, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20210419" } ]

{ "abstract": "Perampanel is an antiepileptic drug that blocks amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors. To date, little is known about the management of perampanel intoxication. We report a case of \"zombielike\" behavior secondary to intentional perampanel overdose. An 18-year-old male with idiopathic generalized epilepsy and focal features presented with aggressive and \"zombielike\" behavior after suicide attempt via intentional perampanel overdose, amounting to approximately 128 mg. Clinical symptoms gradually improved with continuous dexmedetomidine infusion and intravenous lorazepam boluses five days after being admitted to the intensive care unit. While perampanel intoxication has been reported to be associated with central nervous system-related adverse effects, awareness of this association is necessary to prompt more appropriate management tailored to perampanel toxicity.", "affiliations": "Neurology, University of Chicago, Chicago, USA.;Anesthesia, NorthShore University HealthSystem, Evanston, USA.", "authors": "Morsi|Rami Z|RZ|;Katz|Jeffrey A|JA|", "chemical_list": null, "country": "United States", "delete": false, "doi": "10.7759/cureus.14971", "fulltext": "\n==== Front\nCureus\nCureus\n2168-8184\nCureus\n2168-8184\nCureus Palo Alto (CA)\n\n10.7759/cureus.14971\nNeurology\nPsychiatry\n“Zombielike” Aggression in Perampanel Overdose\nMuacevic Alexander\nAdler John R\nMorsi Rami Z 1\nKatz Jeffrey A 2\n1 Neurology, University of Chicago, Chicago, USA\n2 Anesthesia, NorthShore University HealthSystem, Evanston, USA\nRami Z. Morsi ramimorsi93@gmail.com\n11 5 2021\n5 2021\n13 5 e1497111 5 2021\nCopyright © 2021, Morsi et al.\n2021\nMorsi et al.\nhttps://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.\nThis article is available from https://www.cureus.com/articles/59240-zombielike-aggression-in-perampanel-overdose\nPerampanel is an antiepileptic drug that blocks amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors. To date, little is known about the management of perampanel intoxication. We report a case of “zombielike” behavior secondary to intentional perampanel overdose. An 18-year-old male with idiopathic generalized epilepsy and focal features presented with aggressive and “zombielike” behavior after suicide attempt via intentional perampanel overdose, amounting to approximately 128 mg. Clinical symptoms gradually improved with continuous dexmedetomidine infusion and intravenous lorazepam boluses five days after being admitted to the intensive care unit. While perampanel intoxication has been reported to be associated with central nervous system-related adverse effects, awareness of this association is necessary to prompt more appropriate management tailored to perampanel toxicity.\n\nperampanel\nantiepileptic drug\nepilepsy\nsuicide attempt\nadverse effect\nThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\nIntroduction\n\nPerampanel is the first antiepileptic drug in its class to be approved by the Food and Drug Administration for its adjunctive treatment in patients with epilepsy aged 12 years or older, more specifically in those with partial-onset seizures with or without secondary generalization [1]. Perampanel noncompetitively blocks amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors on post-synaptic neurons to reduce excitatory neurotransmission and spread of seizure activity [2,3].\n\nWhile Phase III clinical studies demonstrate perampanel to be safe and well tolerated with continued effectiveness in improving seizure control, dose-dependent central nervous system (CNS) adverse effects have been reported. These dose-dependent treatment-emergent adverse events (TEAEs) include, but are not limited to, dizziness, fatigue, and somnolence [4]. In a pooled analysis of psychiatric and behavioral safety data conducted by Ettinger and colleagues, the most common dose-dependent TEAEs were irritability followed by aggression with overall rates of psychiatric TEAEs being higher in perampanel groups compared to placebo groups [5]. The FYDATA study conducted by Villanueva and colleagues found that patients treated with perampanel, particularly those with prior psychiatric comorbidities, such as hyperactivity and personality disorders, were more likely to experience adverse effects, such as dizziness, somnolence, and irritability, at 12 months [6]. Another study by Lee and colleagues demonstrated that pre-existing depression and a perampanel dose 8 mg daily were potential predictors for aggression. Interestingly, however, they also found that topiramate, when used in conjunction with perampanel, was protective against aggression in patients with focal epilepsy [7].\n\nTo date, little is known about the management of perampanel intoxication. Hoppner and colleagues report a suicide attempt of a 34-year-old female patient with symptomatic focal epilepsy due to tuberous sclerosis who ingested 204 mg of perampanel, which resulted in impaired consciousness and delirium, and was admitted for close monitoring [8]. Wu and colleagues also describe a case of a 40-year-old male patient with prior psychiatric comorbidities and no history of seizure disorder who ingested 60 mg of perampanel in a suicide attempt, resulting in severe aggression and was managed with haloperidol, lorazepam, and dexmedetomidine [9]. Here, we describe the clinical findings in a patient with history of idiopathic generalized epilepsy with focal features who ingested an estimated 128 mg of perampanel in a suicide attempt and presented with bizarre, aggressive, and “zombielike” behavior.\n\nCase presentation\n\nThe patient was an 18-year-old African American male with a history of idiopathic generalized epilepsy with focal features, history of medication noncompliance, no documented formal psychiatric comorbidities, history of substance use, and family history of seizures, who presented after suicide attempt via intentional overdose of perampanel. Patient started taking 8 mg of perampanel daily for 15 months prior to presentation. Patient had multiple trials of antiepileptic medications in the past, including levetiracetam, valproic acid, and lacosamide but patient continued to have breakthrough seizures despite dosage adjustments. On the day of presentation, after a psychosocial stressor provoking the patient to damage the house television, patient ingested his prescription of perampanel, estimated to be 128 mg, which was 16 times his daily dose. Patient was brought into the emergency department via emergency medical services after patient’s mother found him on the floor of his bedroom unresponsive, followed by agitation, paranoia about family members’ remarks about his actions, and physically aggressive behavior. On arrival in the emergency department, his temperature was 97.3oF (36.3oC), blood pressure was 142/88 mm Hg, pulse was 78 beats/min, respiratory rate was 18 breaths/min, and oxygen saturation (SpO2) was 100% on room air. On physical examination, patient was awake and remained agitated. Upon further physical examination, patient was noted to have pupils equal, round, and reactive to light, moist mucous membranes, no increased work of breathing with symmetric chest rise, and warm and dry skin. Patient was moving all extremities in an erratic jerking motion and displaying overtly aggressive and physically harmful behavior toward staff including grabbing and punching anyone in close proximity. Initial laboratory testing was only significant for mild leukocytosis of 11.4*103/µL (normal range: 4.0-10.0*103/µL). Additional testing including serum electrolytes, hepatic function, creatine kinase, blood alcohol level, salicylate level, acetaminophen level, and head computed tomography scan were all negative for any acute abnormalities. Electrocardiogram (EKG) also showed no acute abnormalities, with a corrected QT (QTc) interval of 420 milliseconds. Due to combative and aggressive behavior, patient was placed in four-point restraints, given 0.5 mg of lorazepam, and admitted to the intensive care unit (ICU) for close monitoring and further management. Poison control was contacted for additional assistance in management. \n\nOvernight, patient received a total of four IV boluses of 0.5 mg of lorazepam after increased anger and aggression requiring three staff members to restrain patient for continued violent behavior including thrashing on his bed, kicking, punching, and biting staff members. One staff member had a severe bite wound that required medical intervention in the emergency department. Haloperidol was not initially given at the time for fear of interaction with perampanel, and dexmedetomidine was not given for lack of evidence regarding perampanel intoxication. During the first hospital day, patient was still extremely agitated after requiring a total of 11 mg of IV lorazepam and 5 mg of IV haloperidol throughout the day. His vital signs were within normal limits during this time, but patient had extreme liability between somnolence with blank staring at ceiling followed by severe agitation and violence toward self and others if any person was in close proximity. \n\nOn Day 2 of hospitalization, patient continued to display this labile behavior despite receiving a total of 10 mg of IV lorazepam boluses. Due to the lability of his behavior and the ineffectiveness of lorazepam, he was started on a continuous infusion of dexmedetomidine titrated to 0.9 mcg/kg/h coupled with IV lorazepam boluses amounting to a total of 6 mg after further discussion with the poison control service. On Day 3 of hospitalization, patient’s agitation was controlled with a continuous dexmedetomidine infusion at a rate of 0.7 mcg/kg/h combined with a total of 6 mg of IV lorazepam. On Day 4 of hospitalization, patient remained on continuous dexmedetomidine infusion at a rate of 0.6 mcg/kg/h combined with a total of 8 mg of IV lorazepam. Over the course of Day 5 of hospitalization, the continuous dexmedetomidine infusion was weaned off, and patient only required 2 mg of IV lorazepam. Patient was more awake, oriented, calm, and cooperative. Due to his improvement in mental status and no longer requiring sedation, patient was transferred out of the ICU. Patient did not require any additional sedative medications while on general medicine floors. His blood pressure was 138/83 mm Hg, heart rate was 81 beats/min, respiratory rate was 18 breaths/min, and SpO2 was 98% on room air. During his time on general medicine floors, repeat EKG showed a prolonged QTc of 460 milliseconds but patient continued to be well oriented, calm, and cooperative, and was transferred to psychiatric inpatient services voluntarily. Patient was started on 100 mg of zonisamide daily after discharge and gradually increased to 200 mg daily and has had no seizures or changes in mood or behavior since. \n\nDiscussion\n\nTo the best of our knowledge, this is the first case report of a patient with a documented epilepsy disorder presenting with severe agitation and aggression mimicking zombielike behavior after perampanel overdose who was treated with continuous dexmedetomidine infusion and IV boluses of lorazepam. In New York, synthetic cannabinoid methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA) was associated with a “zombie” outbreak consisting of “zombielike” groaning, slow limb movement, blank stares, and delayed response to questioning [10], but this is the first case report illustrating “zombielike” behavior consisting of moaning, blank stares, erratic limb movement, grabbing, and biting actions associated with perampanel overdose. Revonsuo and colleagues highlight that “Zombiehood” implies automatic behaviors -- whether routine or nonroutine, such as open eyes in a “glazed” appearance, detachment from the environment, bizarre behaviors encompassing aggressive and defensive measures -- can be carried out, even in a state of impaired consciousness [11]. Perampanel has been associated with several psychiatric adverse events as evidently described by Ettinger and colleagues, but there is no clear management plan for perampanel overdose [5]. Wu and colleagues reported a case of a suicide attempt in an individual with prior psychiatric comorbidities but no documented epilepsy and were able to control the patient’s agitation using continuous infusions of dexmedetomidine and haloperidol. This patient described by Wu and colleagues demonstrated improvement in mental status after four days of hospitalization, which was similar to the patient described in this report who needed nearly the same amount of days for the perampanel overdose to gradually clear out of the system [9]. The rationale behind the use of dexmedetomidine was because of its ability to reduce the duration of delirium, agitation, and the need for additional sedation in the ICU setting [12]. Hoppner and colleagues also described a clinical scenario where perampanel overdose did not cause any significant changes in vital signs, such as blood pressure and heart rate, which was similarly seen in the clinical scenario described in this report. However, no clear management plan was described by Hoppner and colleagues [8]. Parsons and colleagues described a case of a 20-year-old treatment-naïve male patient with no prior medical problems who experienced prolonged unconsciousness as a result of a mixed overdose involving perampanel, levothyroxine, and pregabalin [13]. This patient required endotracheal intubation for airway protection, sedation with propofol and fentanyl, and general supportive care [13]. One case was reported by Kim and colleagues regarding a 39-year-old female with documented seizures who experienced altered consciousness after ingesting 40 mg of perampanel and 10,000 mg of valproic acid [14]. This female patient’s hospital stay was further complicated by pulmonary embolism requiring heparin anticoagulation and mechanical ventilation. However, no sedation measures were highlighted in this case study [14].\n\nThe long mean half-life of 105 hours and the dose-dependent CNS adverse effects associated with perampanel should be given extreme caution given the negative consequences this drug has on an individual’s mental status when consumed in supratherapeutic levels [15]. Gidal and colleagues demonstrate that while higher plasma concentrations of perampanel are inversely related to seizure frequency, higher perampanel plasma concentrations are, nevertheless, directly related to adverse effects [16]. While clinical trials have demonstrated that common adverse effects of perampanel include somnolence, fatigue, irritability, headache, dizziness, irritability, ataxia, dysarthria, and memory impairment, there have been increasing cases of suicidality related to perampanel intake [5,17]. Perampanel’s ability to penetrate the blood-brain barrier when ingested orally largely attributes to these CNS adverse effects [18]. It has also been hypothesized that perampanel’s AMPA antagonist properties can alter glutamate levels, and, subsequently, lead to aggressive behavior [19,20].\n\nConclusions\n\nThis case report highlights the need for additional data to understand the pharmacologic effects of perampanel on the CNS as well as uncover mechanisms for managing CNS-related adverse effects induced by perampanel. While continuous dexmedetomidine infusion and lorazepam boluses were considered in this patient’s clinical course, more information is needed to guide medical decisions given the scarcity of the literature on perampanel toxicity-related suicidality and aggression.\n\nHuman Ethics\n\nThe authors have declared that no competing interests exist.\n\nConsent was obtained or waived by all participants in this study\n==== Refs\nReferences\n\n1 Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures Neurology Krauss GL Serratosa JM Villanueva V 1408 1415 78 2012 22517103\n2 Preclinical pharmacology of perampanel, a selective non-competitive AMPA receptor antagonist Acta Neurol Scand Suppl Rogawski MA Hanada T 19 24 2013 23480152\n3 Pharmacodynamic and pharmacokinetic interactions of perampanel and other antiepileptic drugs in a rat amygdala kindling model Seizure Wu T Nagaya Y Hanada T 732 739 23 2014 24997072\n4 Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: results of randomized global phase III study 305 Epilepsia French JA Krauss GL Steinhoff BJ Squillacote D Yang H Kumar D Laurenza A 117 125 54 2013 22905857\n5 Psychiatric and behavioral adverse events in randomized clinical studies of the noncompetitive AMPA receptor antagonist perampanel Epilepsia Ettinger AB LoPresti A Yang H Williams B Zhou S Fain R Laurenza A 1252 1263 56 2015 26140524\n6 Safety, efficacy and outcome-related factors of perampanel over 12 months in a real-world setting: The FYDATA study Epilepsy Res Villanueva V Garcés M López-González FJ 201 210 126 2016 27521586\n7 Effect of perampanel on aggression in patients with refractory focal epilepsy: a 6-month longitudinal study Epilepsy Behav Lee SA Jeon JY Kim HW 106658 102 2020 31743838\n8 Clinical course of intoxication with the new anticonvulsant drug perampanel Epileptic Disord Hoppner AC Fauser S Kerling F 362 364 15 2013 24001596\n9 Severe aggression after perampanel overdose: case report Psychosomatics Wu CC McShane M Huttlin EA Novoa KC 321 324 60 2019 30181001\n10 \"Zombie\" outbreak caused by the synthetic cannabinoid AMB-FUBINACA in New York N Engl J Med Adams AJ Banister SD Irizarry L Trecki J Schwartz M Gerona R 235 242 376 2017 27973993\n11 The zombies among us Beyond Dissociation: Interaction Between Dissociated Implicit and Explicit Processing Revonsuo A Johanson M Wedlund J Chaplin J 331 352 Amsterdam John Benjamins Publishing Co 22 2000\n12 Dexmedetomidine reduces the risk of delirium, agitation and confusion in critically Ill patients: a meta-analysis of randomized controlled trials J Cardiothorac Vasc Anesth Pasin L Landoni G Nardelli P 1459 1466 28 2014 25034724\n13 Prolonged unconsciousness in perampanel overdose BMJ Case Rep Parsons G Bailey J Bailey F Brzezicki M 0 12 2019\n14 Prolonged stupor in perampanel overdose and pharmacokinetic considerations J Epilepsy Res Kim S Kim TE Kim D Kim DW 87 89 8 2018 30809502\n15 FYCOMPA US Prescribing Information 42021 2016 https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202834s011lbl.pdf\n16 Concentration-effect relationships with perampanel in patients with pharmacoresistant partial-onset seizures Epilepsia Gidal BE Ferry J Majid O Hussein Z 1490 1497 54 2013 23772853\n17 Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies Epilepsia Steinhoff BJ Ben-Menachem E Ryvlin P 1481 1489 54 2013 23663001\n18 Blood-brain Barrier in Drug Discovery: Optimizing Brain Exposure of CNS Drugs and Minimizing Brain Side Effects for Peripheral Drugs Di L Kerns EH Hoboken, NJ John Wiley & Sons 2015 https://www.google.co.in/books/edition/Blood_Brain_Barrier_in_Drug_Discovery/JzEaBgAAQBAJ?hl=en&gbpv=1&dq=Di+L,+Kerns+EH:+Blood-brain+barrier+in+drug+discovery:+optimizing+brain+exposure+of+CNS+drugs+and+minimizing+brain+side+effects+for+peripheral+drugs.+John+Wiley+%26+Sons%3B+2015&printsec=frontcover\n19 Involvement of prefrontal AMPA receptors in encounter stimulation-induced hyperactivity in isolation-reared mice Int J Neuropsychopharmacol Araki R Ago Y Hasebe S 883 893 17 2014 24405605\n20 Acute effects of AMPA-type glutamate receptor antagonists on intermale social behavior in two mouse lines bidirectionally selected for offensive aggression Pharmacol Biochem Behav Vekovischeva OY Aitta-aho T Verbitskaya E Sandnabba K Korpi ER 241 249 87 2007 17537494\n\n", "fulltext_license": "CC BY", "issn_linking": "2168-8184", "issue": "13(5)", "journal": "Cureus", "keywords": "adverse effect; antiepileptic drug; epilepsy; perampanel; suicide attempt", "medline_ta": "Cureus", "mesh_terms": null, "nlm_unique_id": "101596737", "other_id": null, "pages": "e14971", "pmc": null, "pmid": "34123667", "pubdate": "2021-05-11", "publication_types": "D002363:Case Reports", "references": "24405605;27521586;23772853;22905857;31743838;24997072;23480152;30181001;25034724;30809502;26140524;23663001;27973993;22517103;17537494;24001596;31791997", "title": "\"Zombielike\" Aggression in Perampanel Overdose.", "title_normalized": "zombielike aggression in perampanel overdose" }

[ { "companynumb": "US-EISAI MEDICAL RESEARCH-EC-2020-085568", "fulfillexpeditecriteria": "1", "occurcountry": "US", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "PERAMPANEL" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "202834", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLETS", "drugdosagetext": null, "drugenddate": "2019", "drugenddateformat": "602", "drugindication": "IDIOPATHIC GENERALISED EPILEPSY", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2019", "drugstartdateformat": "602", "drugstructuredosagenumb": "2", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FYCOMPA" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PERAMPANEL" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "202834", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLETS", "drugdosagetext": "16 TABLETS OF 8 MG (TOTAL DOSE: 128 MG)", "drugenddate": "20201216", "drugenddateformat": "102", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "20201216", "drugstartdateformat": "102", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FYCOMPA" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PERAMPANEL" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "202834", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLETS", "drugdosagetext": "UP?TITRATION (DOSE AND FREQUENCY UNKNOWN)", "drugenddate": "2020", "drugenddateformat": "602", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2019", "drugstartdateformat": "602", "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FYCOMPA" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PERAMPANEL" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "202834", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLETS", "drugdosagetext": null, "drugenddate": "2020", "drugenddateformat": "602", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": "8", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FYCOMPA" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PERAMPANEL" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "202834", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLETS", "drugdosagetext": null, "drugenddate": "20201215", "drugenddateformat": "102", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": "8", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FYCOMPA" }, { "actiondrug": "1", "activesubstance": { "activesubstancename": "PERAMPANEL" }, "drugadditional": "1", "drugadministrationroute": "048", "drugauthorizationnumb": "202834", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "TABLETS", "drugdosagetext": null, "drugenddate": "2020", "drugenddateformat": "602", "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "2020", "drugstartdateformat": "602", "drugstructuredosagenumb": "8", "drugstructuredosageunit": "003", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FYCOMPA" } ], "patientagegroup": "5", "patientonsetage": "18", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Intentional overdose", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Suicide attempt", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Intentional product misuse", "reactionmeddraversionpt": "24.0", "reactionoutcome": "6" }, { "reactionmeddrapt": "Aggression", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Altered state of consciousness", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" }, { "reactionmeddrapt": "Agitation", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20201216" } }, "primarysource": { "literaturereference": "MORSI R, KATZ J. ^ZOMBIELIKE^ AGGRESSION IN PERAMPANEL OVERDOSE. CUREUS. 2021 MAY 11?13(5):E14971:. DOI:10.7759/CUREUS.14971", "literaturereference_normalized": "zombielike aggression in perampanel overdose", "qualification": "1", "reportercountry": "US" }, "primarysourcecountry": "US", "receiptdate": "20210623", "receivedate": "20201223", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 18657299, "safetyreportversion": 2, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": 1, "seriousnesslifethreatening": null, "seriousnessother": null, "transmissiondate": "20210717" } ]

{ "abstract": "Tumor necrosis factor-alpha (TNF-α) inhibitors are widely used to treat various inflammatory conditions, where they have demonstrated excellent efficacy and tolerability. However, increased risk of infections is one of the most important concerns associated with these agents. Reactivation of tuberculosis and fungal infections have emerged as significant infective complications of anti-TNF-α therapy. Cryptococcus infection is an opportunistic fungal infection that can occur in patients receiving anti-TNF-α treatment. We report a rare case of isolated pulmonary cryptococcosis in a patient undergoing anti-TNF-α therapy for Crohn's disease. Our case should alert clinicians to the increased incidence and atypical presentation of pulmonary cryptococcosis in patients receiving anti-TNF-α treatment.", "affiliations": "Hamad Medical Corporation, Pulmonology Department, Qatar.;Hamad Medical Corporation, Pulmonology Department, Qatar.;Hamad Medical Corporation, Pulmonology Department, Qatar.;Hamad Medical Corporation, Pulmonology Department, Qatar.;Hamad Medical Corporation, Infectious Diseases Department, Qatar.;Hamad Medical Corporation, Pulmonology Department, Qatar.;Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar.", "authors": "Hussein|Mousa|M|;Haq|Irfan Ul|IU|;Hameed|Mansoor|M|;Alabbas|Abbas|A|;Hadi|Hamad Abdel|HA|;Elarabi|Anam|A|;Al-Bozom|Issam|I|", "chemical_list": null, "country": "England", "delete": false, "doi": "10.1016/j.rmcr.2021.101459", "fulltext": "\n==== Front\nRespir Med Case Rep\nRespir Med Case Rep\nRespiratory Medicine Case Reports\n2213-0071\nElsevier\n\nS2213-0071(21)00121-0\n10.1016/j.rmcr.2021.101459\n101459\nCase Report\nIsolated pulmonary cryptococcosis in a patient with Crohn's disease treated with infliximab: A case report and literature review\nHussein Mousa Mhussein11@hamad.qa\na∗\nHaq Irfan Ul a\nHameed Mansoor a\nAlabbas Abbas a\nHadi Hamad Abdel b\nElarabi Anam a\nAl-Bozom Issam c\na Hamad Medical Corporation, Pulmonology Department, Qatar\nb Hamad Medical Corporation, Infectious Diseases Department, Qatar\nc Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar\n∗ Corresponding author. Doha, Qatar. Mhussein11@hamad.qa\n24 6 2021\n2021\n24 6 2021\n33 10145913 4 2021\n7 6 2021\n16 6 2021\n© 2021 The Authors\n2021\nhttps://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).\nTumor necrosis factor-alpha (TNF-α) inhibitors are widely used to treat various inflammatory conditions, where they have demonstrated excellent efficacy and tolerability. However, increased risk of infections is one of the most important concerns associated with these agents. Reactivation of tuberculosis and fungal infections have emerged as significant infective complications of anti-TNF-α therapy. Cryptococcus infection is an opportunistic fungal infection that can occur in patients receiving anti-TNF-α treatment. We report a rare case of isolated pulmonary cryptococcosis in a patient undergoing anti-TNF-α therapy for Crohn's disease. Our case should alert clinicians to the increased incidence and atypical presentation of pulmonary cryptococcosis in patients receiving anti-TNF-α treatment.\n\nKeywords\n\nTumor necrosis factor-alpha (TNF-α) inhibitors\nInfliximab\nCrohn's disease\nCryptococcosis\nFungal infections\n==== Body\nIntroduction\n\nCrohn's disease (CD) is a chronic inflammatory condition affecting any part of the gastrointestinal (GI) tract. It is characterized by periods of relapse and remission. Chronic bowel inflammation often leads to complications such as fistulas and strictures. Anti-TNF-α agents are proven to help CD's most severe cases, particularly thoserefractory to steroids [1]. Anti-TNF-α agents are generally well tolerated but areassociated with various side effects, with increased susceptibility to infections being a significant concern following their initiation.\n\nCryptococcosis is one of the fungal infections usually diagnosed in immunocompromised patients. Long-term immunosuppressive therapy is a known risk factor for developing pulmonary cryptococcosis [[2], [3], [4]]. In Immunocompetent patients, cryptococcal infection usually results in mild chest symptoms such as low-grade fever and minimal cough, while immunocompromised patients experience more severe chest symptoms such as high-grade fever, severe chronic cough, dyspnea, and hemoptysis (5). The significant variation in the clinical and radiological manifestations of cryptococcal infection often leads to a delayed or incorrect diagnosis. A delay in the diagnosis and treatment of such infections may result in disseminated disease. We report an uncommon case of pulmonary cryptococcosis developing during therapy with infliximab in a patient with advanced Crohn's disease.\n\nCase report\n\nA 54-year old male was diagnosed as having Crohn's disease in 2012 when he presented with symptoms suggestive of intestinal obstruction and underwent a right hemicolectomy and a jejunal stricture resection. Histopathology of the resected tissue showed extensive ulceration of the jejunum and the ascending colon, chronic crypt architectural distortion, and crypt abscesses. Two months later, he re-presented with abdominal pain and was found to have narrowing at the anastomotic site on coloscopy. The biopsy of the anastomotic site revealed severe inflammation and ulceration and therefore started on steroids and azathioprine.\n\nAzathioprine was later substituted with methotrexate due to gastrointestinal intolerance and leucopenia. He was started on infliximab in July 2019 (5 mg/kg Intravenous every eight weeks) because of his progressive disease. In October 2020, he was admitted to our department with a one-month history of fever, fatigue, and productive cough with yellowish sputum. He was febrile with a temperature of 39 °C, and a chest examination revealed bilateral coarse crackles over mid-lower lung zones. He had no pets and no known contact with birds. His laboratory investigations are summarized in (Table 1). A Chest x-ray showed a right-sided ill-defined nodular infiltrate (Fig. 1A). He was initially treated as a community-acquired chest infection with ceftriaxone and azithromycin. A computerized tomography (CT) chest was requested as there was an inadequate clinical response to treatment. The CT scan revealed scattered nodules and patchy ground-glass opacities in the right lower lobe (Fig. 1B,C,D). Subsequently, bronchoscopy with transbronchial biopsies from the right lower zone was performed. Bronchoalveolar lavage showed 55% lymphocytes and a positive culture for cryptococcus neoformans. Histopathology was noticeable for non-necrotizing granulomatous inflammation, and Grocott stain identified rounded organisms with a thick capsule consistent with cryptococcus neoformans (Fig. 2). Based on the absence of neurological symptoms, lumbar puncture was not carried out. He was started on a 6- month course of daily oral fluconazole. At one month's follow-up, he reported total resolution of his symptoms with a chest X-ray showing mild regression of the right-sided infiltrates.Table 1 Relevant lab investigations, including infection workup.\n\nTable 1Investigation\tResult\tNormal range\t\nWBC count\t4.9\t4–10 × 10^3/uL\t\nPlatelet count\t290\t15–400 × 10^3/uL\t\nHb\t14\t13-17 gm/dL\t\nEosinophil count\t0.1\t0.0–0.5 × 10^3/uL\t\nCreatinine\t66\t62–106 μmol/L\t\nSodium\t139\t136–145 mmol/L\t\nAlanine aminotransferase\t19\t0–41 U/L\t\nC- Reactive protein\t108\t0–5 mg/L\t\nProcalcitonin\t0.12\t<0.5 ng/ml\t\nAlbumin\t30\t35-50 gm/L\t\nLactate dehydrogenase\t169\t135–225 U/L\t\nTotal protein\t69\t66-87 gm/L\t\nQuantiFERON gold plus\tNegative\t\t\nBlood cultures\tNo growth\t–\t\nUrine culture\tNo growth\t–\t\nCommon Viruses panel\tNegative\t–\t\nSputum AFB smear, PCR, and culture\tNegative\t–\t\nSARS-Cov 2 PCR\tNegative\t–\t\nHIV antigen/antibody ELISA\tNon-reactive\t\t\n\nFig. 1 1A Chest X-ray Image showing inhomogeneous patchy infiltrates in the right mid and lower zones. (1B,C,D) CT chest Image showing multiple nodules in the right lower lobe with patchy ground-glass opacifications.\n\nFig. 1\n\nFig. 2 2A: lung tissue showing non-necrotizing granulomatous inflammation (arrow) 2B showing cryptococcus organism with the characteristic thick capsule as stained by GMS fungal stain.\n\nFig. 2\n\nDiscussion\n\nPulmonary cryptococcosis is an opportunistic fungal infection that has become an emerging disease in immunocompromised and immunocompetent patients. It is caused by encapsulated fungi cryptococcus gattii and C. neoformans commonly found in bird droppings, soil, and decaying wood. However, the source of the infection is not always evident, like in our case [6].\n\nCryptococcal infections in humans likely occur when the organism is aerosolized and inhaled. Human disease caused by this fungus ranges from asymptomatic pulmonary colonization to life-threatening meningitis and overwhelming cryptococcemia [7]. Tumor necrosis factor-alpha (TNF-α) inhibitors are increasingly being used for various inflammatory diseases. The use of these agents is associated with an increased risk of opportunistic infections like non-tuberculous mycobacteria, fungi (Pneumocystis jiroveci, Candida sp, Aspergillus, Cryptococcus, Histoplasma), opportunistic bacteria (Nocardia), parasites (Leishmania), and virus (e.g., Cytomegalovirus, Human Herpesvirus 8 [HHV 8]) infections. These infections usually occur within the first months of therapy [8]. The proposed mechanism for the increased risk of fungal infections in patients taking anti-TNF-α suppresses T-helper cells type 1 and reduces interleukin-12 and interferon-gamma [9]. Cryptococcosis was observed after a median interval of three months in many cases [10]. Our patient developed respiratory symptoms after receiving five infusions of infliximab. However, the simultaneous use of other immunosuppressive agents (steroids and azathioprine) might.\n\nHave decreased the immune response and contributed to the development of cryptococcosis in our patient.\n\nPulmonary cryptococcosis usually presents with nonspecific symptoms of cough, dyspnea, chest pain, and fever. The radiological presentation can range from asymptomatic nodular disease to diffuse interstitial pattern making differentiation from other respiratory disorders quite challenging [11]. Identifying a positive culture of cryptococcus from bronchoalveolar lavage (BAL) together with the typical findings on tissue biopsies are the vital diagnostic approaches [12]. Histological staining with hematoxylin and eosin (H&E), Grocott or Gomori methenamine silver (GMS), and periodic acid-Schiff (PAS) are used to detect cryptococcus that appears as narrow-based budding yeasts (4–10 μm). Antigen tests for cryptococcus from blood or culture are occasionally positive in disseminated cryptococcal infection [12]. The role of lumbar puncture in non-HIV-infected patients with cryptococcosis is debatable but can be deferred in patients without meningeal signs [13]. We preferred not to do a lumbar puncture on our patient as he didn't have any neurological signs or symptoms.\n\nAfter a careful PubMed literature review, we found only five pulmonary cryptococcosis cases in patients with Crohn's disease treated with anti-TNF-α therapy in the last 15 years. The clinical characteristics of pulmonary cryptococcosis in these patients are compared with our case (Table 2). One of the six patients received adalimumab, while the rest were treated with infliximab. It is noteworthy to mention that five out of 6 patients received other immunosuppressive therapy in addition to anti-TNF-α therapy as well. Toruner et al. in their paper, reported that infliximab, when used in combination with steroids and Azathioprine/6-mercaptopurine, is associated with an increased risk of opportunistic infections [14].Table 2 Clinical characteristics of pulmonary cryptococcosis in Crohn's disease patients receiving TNF-a inhibitor.\n\nTable 2Study\nReference\tAge in years\tSex\tSymptoms\tAnti TNF -alpha\ntherapy\tDuration of therapy/Number of doses\tConcurrent\nImmunosuppressive therapy\tCT chest findings\tMethod of diagnosis\tBird related exposure\t\nRehman et al.\n2008 [15]\t61\tMale\tNone\tInfliximab\t2.5\nYears\tprednisolone, azathioprine\tMultiple\nNodules\tLung Biopsy\tno known exposure\t\nOsawa and Singh 2010 [16]\t53\tMale\tFever, diarrhea\tInfliximab\tThree years\tprednisolone, azathioprine\tMultiple\nNodules\tColon Biopsy\nCSF culture\tno known exposure\t\nHirai et al., 2011 [17]\t39\tMale\tNone\tInfliximab\tFive doses\tNone\tLeft upper lobe\nNodule\tLobectomy\tpigeons\t\nTakazono et al.\n2012 [18]\t35\tMale\tHigh grade fever\tInfliximab\tEight doses\tprednisolone,\tLeft lower lobe\nNodule\tBAL cryptococcal\nantigen\tno known exposure\t\nJ-B.\nFraison et al. [19]\t54\tMale\tFever, cough, dyspnea\tAdalimumab\tThree doses\tprednisolone, azathioprine\tMultiple nodules,\nEnlarged subcarinal\nlymph node\tPositive BAL culture\tchicken manure\t\nPresent case\t54\tMale\tFever, cough, fatigue\tInfliximab\tFive doses\tprednisolone, methotrexate\tRight lower lobe\nnodules\tLung biopsy\tno known exposure\t\n\nThe drug of choice for isolated pulmonary cryptococcosis is fluconazole [20]. Alternative agents include oral itraconazole or voriconazole [5]. Monitoring of serum cryptococcal antigen titers is not required. Pulmonary cryptococcosis in non-HIV patients has a good prognosis if properly managed. Pulmonary cryptococcosis has not led to any deaths, relapses, or dissemination among non-HIV patients in China, with a follow-up of 2–11 years [21].\n\nConclusion\n\nIsolated pulmonary cryptococcal infections, although rare, can occur in patients receiving anti-TNF-α therapy to treat underlying inflammatory conditions like Crohn's disease. Clinicians need to be aware that it can present with an atypical clinico-radiological picture, resulting in delayed diagnosis and exposing one to the possibility of disseminated infection.\n\nDeclaration of competing interest\n\nThere is no conflict of interest for this publication by all authors.\n\nAcknowledgment\n\nOpen access publication funded by the Qatar National Library.\n==== Refs\nReferences\n\n1 Sandborn W.J. Rutgeerts P. Enns R. Hanauer S.B. Colombel J.F. Panaccione R. D'Haens G. Li J. Rosenfeld M.R. Kent J.D. Pollack P.F. Adalimumab induction therapy for Crohn's disease previously treated with infliximab: a randomized trial Ann. Intern. Med. 146 12 2007 Jun 19 829 838 10.7326/0003-4819-146-12-200706190-00159 Epub 2007 Apr 30. PMID: 17470824 17470824\n2 Liu K. Ding H. Xu B. Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary cryptococcosis J. Thorac. Dis. 8 10 2016 2813 2821 10.21037/jtd.2016.10.36 27867557\n3 Kohno S. Kakeya H. Izumikawa K. Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan J. Infect. Chemother. 21 1 2015 23 30 10.1016/j.jiac.2014.08.025 25444673\n4 Xie X. Xu B. Yu C. Clinical analysis of pulmonary cryptococcosis in non-HIV patients in south China Int. J. Clin. Exp. Med. 8 3 2015 3114 3119 Published 2015 Mar 15 26064200\n5 Kanjanapradit K. Kosjerina Z. Tanomkiat W. Keeratichananont W. Panthuwong S. Pulmonary cryptococcosis presenting with lung mass: report of 7 cases and review of literature Clin. Med. Insights Pathol. 10 2017 1179555717722962 10.1177/1179555717722962 Published 2017 Aug 4\n6 Levitz S.M. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis Rev. Infect. Dis. 13 6 1991 Nov-Dec 1163 1169 10.1093/clinids/13.6.1163 PMID: 1775849 1775849\n7 Nadrous H.F. Antonios V.S. Terrell C.L. Ryu J.H. Pulmonary cryptococcosis in nonimmunocompromised patients Chest 124 2003 2143 2147 10.1016/s0012-3692(15)31671-8 14665493\n8 Marie I. Guglielmino E. Infections opportunistes non tuberculeuses au cours des traitements par les anti-TNFalpha [Non tuberculous anti-TNF associated opportunistic infections] French Rev. Med. Interne 31 5 2010 May 353 360 10.1016/j.revmed.2009.04.010 Epub 2010 Apr 8. PMID: 20381217 20381217\n9 Herring A.C. Lee J. McDonald R.A. Toews G.B. Huffnagle G.B. Induction of interleukin-12 and gamma interferon requires tumor necrosis factor alpha for protective T1-cell-mediated immunity to pulmonary cryptococcus neoformans infection Infect. Immun. 70 2002 2959 2964 12010985\n10 Tsiodras S. Samonis G. Boumpas D.T. Kontoyiannis D.P. Fungal infections complicating tumor necrosis factor alpha blockade therapy Mayo Clin. Proc. 83 2 2008 Feb 181 194 PMID: 18241628 18241628\n11 Chang W.C. Tzao C. Hsu H.H. Lee S.C. Huang K.L. Tung H.J. Chen C.Y. Pulmonary cryptococcosis: comparison of clinical and radiographic characteristics in immunocompetent and immunocompromised patients Chest 129 2006 333 340 16478849\n12 Setianingrum Findra Rautemaa-Richardson Riina Denning David W. Pulmonary cryptococcosis: a review of pathobiology and clinical aspects Med. Mycol. 57 Issue 2 February 2019 133 150 10.1093/mmy/myy086 30329097\n13 Huang S.H. Chuang Y.C. Lee Y.C. Lumbar puncture for non-HIV-infected non-transplant patients with cryptococcosis: should it be mandatory for all? Published 2019 Aug 22 PloS One 14 8 2019 e0221657 10.1371/journal.pone.0221657 (21) Limper AH, Knox KS, Sarosi GA et al.An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011; 183: 96-128\n14 Toruner M. Loftus E.V. Jr. Harmsen W.S. Zinsmeister A.R. Orenstein R. Sandborn W.J. Colombel J.F. Egan L.J. Risk factors for opportunistic infections in patients with inflammatory bowel disease Gastroenterology 134 4 2008 Apr 929 936 10.1053/j.gastro.2008.01.012 Epub 2008 Jan 11. PMID: 18294633 18294633\n15 Rehman T. Ali J. Lopez F.A. A 61-year-old man withasymptomatic, bilateral lung masses J. La. State Med. Soc. 160 2008 309 314 19283977\n16 Osawa R. Singh N. Colitis as a manifestation of infliximab- associated disseminated cryptococcosis Int. J. Infect. Dis. 14 2010 e436 440 19660974\n17 Hirai F. Matsui T. Ishibashi Y. Asymptomatic pulmonary cryptococcosis in a patient with Crohn's disease on infliximab: case report Inflamm. Bowel Dis. 17 2011 1637 1638 21674724\n18 Takazono T. Izumikawa K. Yoshioka S. Matsuo N. Yamakawa M. Suyama N. Kohno S. Possible pulmonary cryptococcosis in a patient with Crohn's disease during anti-tumor necrosis factor-alpha treatment: a case report and literature review Jpn. J. Infect. Dis. 65 5 2012 461 464 10.7883/yoken.65.461 PMID: 22996229 22996229\n19 Fraison Jean-Baptiste Guilpain Philippe Schiffmann Aurélie Veyrac Michel Le Moing Vincent Rispail Philippe Le Quellec Alain Pulmonary cryptococcosis in a patient with Crohn's disease treated with prednisone, azathioprine and adalimumab: exposure to chicken manure as a source of contamination journal of Crohn's and Colitis 7 Issue 1 February 2013 e11 e14 10.1016/j.crohns.2012.04.016\n20 Dromer F. Mathoulin S. Dupont B. Brugiere O. Letenneur L. Comparison of the efficacy of amphotericin B and fluconazole in the treatment of cryptococcosis in human immunodeficiency virus-negative patients: retrospective analysis of 83 cases. French Cryptococcosis Study Group Clin. Infect. Dis. 22 Suppl 2 1996 May S154 S160 10.1093/clinids/22.supplement_2.s154 PMID: 8722844 8722844\n21 Yu J.Q. Tang K.J. Xu B.L. Xie C.M. Light R.W. Pulmonary cryptococcosis in non- AIDS patients Braz. J. Infect. Dis. 16 6 2012 Nov-Dec 531 539 10.1016/j.bjid.2012.07.004 Epub 2012 Nov 13. PMID: 231 23154046\n\n", "fulltext_license": "CC BY", "issn_linking": "2213-0071", "issue": "33()", "journal": "Respiratory medicine case reports", "keywords": "Crohn's disease; Cryptococcosis; Fungal infections; Infliximab; Tumor necrosis factor-alpha (TNF-α) inhibitors", "medline_ta": "Respir Med Case Rep", "mesh_terms": null, "nlm_unique_id": "101604463", "other_id": null, "pages": "101459", "pmc": null, "pmid": "34401295", "pubdate": "2021", "publication_types": "D002363:Case Reports", "references": "12010985;30329097;22996229;14665493;26064200;8722844;18294633;22647638;16478849;31437259;28814908;20381217;18241628;23154046;1775849;19283977;17470824;21674724;27867557;19660974;25444673", "title": "Isolated pulmonary cryptococcosis in a patient with Crohn's disease treated with infliximab: A case report and literature review.", "title_normalized": "isolated pulmonary cryptococcosis in a patient with crohn s disease treated with infliximab a case report and literature review" }

[ { "companynumb": "QA-JNJFOC-20210841911", "fulfillexpeditecriteria": "1", "occurcountry": "QA", "patient": { "drug": [ { "actiondrug": null, "activesubstance": { "activesubstancename": "FLUCONAZOLE" }, "drugadditional": null, "drugadministrationroute": "048", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "UNKNOWN", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": "804", "drugintervaldosageunitnumb": "1", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": "1", "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "FLUCONAZOLE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE." }, { "actiondrug": null, "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": null, "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "2", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": null, "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE." }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INFLIXIMAB" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": "103772", "drugbatchnumb": "UNKNOWN", "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "SOLUTION FOR INFUSION", "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "CROHN^S DISEASE", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201907", "drugstartdateformat": "610", "drugstructuredosagenumb": "5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "REMICADE" } ], "patientagegroup": "5", "patientonsetage": "54", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pneumonia cryptococcal", "reactionmeddraversionpt": "24.0", "reactionoutcome": "1" } ], "summary": null }, "primarysource": { "literaturereference": "HUSSEIN M, HAMEED M, ALABBAS A, HADI H, ELARABI A, AL?BOZOM I, HAQ I. ISOLATED PULMONARY CRYPTOCOCCOSIS IN A PATIENT WITH CROHN^S DISEASE TREATED WITH INFLIXIMAB: A CASE REPORT AND LITERATURE REVIEW. RESPIR MED CASE REP.", "literaturereference_normalized": "isolated pulmonary cryptococcosis in a patient with crohn s disease treated with infliximab a case report and literature review", "qualification": "3", "reportercountry": "QA" }, "primarysourcecountry": "QA", "receiptdate": "20210827", "receivedate": "20210827", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 19752748, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": null, "seriousnessdeath": null, "seriousnessdisabling": null, "seriousnesshospitalization": null, "seriousnesslifethreatening": null, "seriousnessother": 1, "transmissiondate": "20211014" }, { "companynumb": "QA-SUN PHARMACEUTICAL INDUSTRIES LTD-2022RR-323977", "fulfillexpeditecriteria": "1", "occurcountry": "QA", "patient": { "drug": [ { "actiondrug": "1", "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": "1", "drugadministrationroute": "065", "drugauthorizationnumb": "201749", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Crohn^s disease", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": "3", "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": "065", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": "UNK", "drugenddate": null, "drugenddateformat": null, "drugindication": "Crohn^s disease", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE" } ], "patientagegroup": null, "patientonsetage": "54", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Disease progression", "reactionmeddraversionpt": "24.1", "reactionoutcome": "6" }, { "reactionmeddrapt": "Cryptococcosis", "reactionmeddraversionpt": "24.1", "reactionoutcome": "2" } ], "summary": null }, "primarysource": { "literaturereference": "Hussein M, Haq IU, Hameed M, Alabbas A, Hadi HA, Elarabi A. Isolated pulmonary cryptococcosis in a patient with Crohn^s disease treated with infliximab: A case report and literature review. Respirat Med Case Report. 2021;33:101459", "literaturereference_normalized": "isolated pulmonary cryptococcosis in a patient with crohn s disease treated with infliximab a case report and literature review", "qualification": "3", "reportercountry": "QA" }, "primarysourcecountry": "QA", "receiptdate": "20220121", "receivedate": "20220121", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20359520, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 1, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" }, { "companynumb": "QA-MLMSERVICE-20211230-3293576-1", "fulfillexpeditecriteria": "1", "occurcountry": "QA", "patient": { "drug": [ { "actiondrug": "5", "activesubstance": { "activesubstancename": "METHOTREXATE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": "040716", "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Crohn^s disease", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "METHOTREXATE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "PREDNISOLONE" }, "drugadditional": "3", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Crohn^s disease", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "PREDNISOLONE" }, { "actiondrug": "5", "activesubstance": { "activesubstancename": "INFLIXIMAB" }, "drugadditional": "3", "drugadministrationroute": "042", "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": "Infusion", "drugdosagetext": "CUMULATIVE DOSE: 5 DOSAGE FORM", "drugenddate": null, "drugenddateformat": null, "drugindication": "Crohn^s disease", "drugintervaldosagedefinition": "803", "drugintervaldosageunitnumb": "8", "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": "201907", "drugstartdateformat": "610", "drugstructuredosagenumb": "5", "drugstructuredosageunit": "007", "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "INFLIXIMAB" }, { "actiondrug": "6", "activesubstance": { "activesubstancename": "AZATHIOPRINE" }, "drugadditional": "4", "drugadministrationroute": null, "drugauthorizationnumb": null, "drugbatchnumb": null, "drugcharacterization": "1", "drugcumulativedosagenumb": null, "drugcumulativedosageunit": null, "drugdosageform": null, "drugdosagetext": null, "drugenddate": null, "drugenddateformat": null, "drugindication": "Crohn^s disease", "drugintervaldosagedefinition": null, "drugintervaldosageunitnumb": null, "drugrecurreadministration": null, "drugrecurrence": null, "drugseparatedosagenumb": null, "drugstartdate": null, "drugstartdateformat": null, "drugstructuredosagenumb": null, "drugstructuredosageunit": null, "drugtreatmentduration": null, "drugtreatmentdurationunit": null, "medicinalproduct": "AZATHIOPRINE" } ], "patientagegroup": null, "patientonsetage": "54", "patientonsetageunit": "801", "patientsex": "1", "patientweight": null, "reaction": [ { "reactionmeddrapt": "Pneumonia cryptococcal", "reactionmeddraversionpt": "24.1", "reactionoutcome": "2" } ], "summary": { "narrativeincludeclinical": "CASE EVENT DATE: 20200901" } }, "primarysource": { "literaturereference": "Hussein M, Haq IU, Hameed M, Alabbas A, Hadi HA, Elarabi A. Isolated pulmonary cryptococcosis in a patient with Crohn^s disease treated with infliximab: A case report and literature review. Respiratory Medicine Case Reports. 2021;33:Article Number 101459.", "literaturereference_normalized": "isolated pulmonary cryptococcosis in a patient with crohn s disease treated with infliximab a case report and literature review", "qualification": "1", "reportercountry": "QA" }, "primarysourcecountry": "QA", "receiptdate": "20220110", "receivedate": "20220110", "receiver": { "receiverorganization": "FDA", "receivertype": "6" }, "reporttype": "1", "safetyreportid": 20316761, "safetyreportversion": 1, "sender": { "senderorganization": "FDA-Public Use", "sendertype": "2" }, "serious": 1, "seriousnesscongenitalanomali": 2, "seriousnessdeath": 2, "seriousnessdisabling": 2, "seriousnesshospitalization": 2, "seriousnesslifethreatening": 2, "seriousnessother": 1, "transmissiondate": "20220423" } ]