Sex: M
Vaccine: COVID19
Symptoms: Confusional state, Fall, Foot fracture, Haemoglobin, Hypersensitivity
Clinical narrative: Increasing tingling mostly in his feet; Confusion; Reaction to the second dose of the COVID vaccine; having more vivid dreams; gained weight; deconditioning; used suction since the last visit and thought it was more likely to be the result of excess secretions from allergies; Two falls; Broken toe; Weaker; Myasthenia gravis; This is a solicited report received from contactable reporter(s) (Physician). Other Case identifier(s): A202209088 (Agency).  An elderly male patient received BNT162b2 (BNT162B2), on 25Jan2021 as dose 2, 0.3 ml single (Lot number: FE3592), on 25Jan2021 as dose 2, 0.3 ml single (Lot number: EN6201) and on 25Jan2021 as dose 2, 0.3 ml single (Lot number: EI8982), all intramuscular for covid-19 immunisation; eculizumab (SOLIRIS), first regimen since Mar2020 (Batch/Lot number: unknown) at 300 mg (300 mg, every 2 weeks) and second regimen from Mar2021 (Batch/Lot number: unknown) to 25Jul2022, all intravenous for myasthenia gravis. The patient's relevant medical history included: "Hypertension" (ongoing); "Hyperlipidemia" (ongoing); "Type 2 diabetes mellitus" (ongoing); "Parkinson's disease", start date: 2017 (ongoing), notes: movement disorders; "Swallowing difficult", start date: Jun2017 (unspecified if ongoing), notes: issues with swallow/ having more difficulty with heartier foods (e.g. chicken); "Choking" (unspecified if ongoing), notes: several episodes/Two episodes required ED; "Fatigue" (ongoing); "CPAP (Positive airway pressure therapy)" (unspecified if ongoing), notes: uses his CPAP even when resting; "Binocular diplopia" (ongoing); "Ptosis" (unspecified if ongoing), notes: occasional; "Walker user" (unspecified if ongoing), notes: rolling walker; "Wheelchair user" (ongoing); "Coughing" (unspecified if ongoing), notes: coughing spells while eating; "Mucus discharge" (unspecified if ongoing), notes: excessive mucus; "Sialorrhea" (ongoing), notes: excessive saliva production/exacerbation; "UTI" (ongoing); "Respiratory syncytial virus infection" (unspecified if ongoing); "Dyspnea exertional" (unspecified if ongoing), notes: shortness of breath with activity; "Hypercholesteremia" (unspecified if ongoing); "Foley catheter" (unspecified if ongoing), notes: in place; "Enlarged prostate" (unspecified if ongoing); "Sleep apnea" (unspecified if ongoing); "Vitamin B12 deficiency" (ongoing); "Condom catheter placement" (unspecified if ongoing), notes: occasionally; "Appendectomy" (unspecified if ongoing); "Colonoscopy", start date: 03Feb2020 (unspecified if ongoing); "Esophagogastroduodenoscopy", start date: 19Jul2019 (unspecified if ongoing); "Fusion lumbar spine", start date: 2014 (unspecified if ongoing), notes: Fusion lumbar spine (Spinal fusion surgery); L4-L5; "Fusion lumbar spine", start date: 2013 (unspecified if ongoing), notes: Fusion lumbar spine (Spinal fusion surgery); L4-L5 unsuccessful; "Tobacco user", start date: 1964, stop date: 2009, notes: Smoking status: Former Smoker, Packs/day: 2.00; Type: Cigarettes; Years since quitting: 13.5; "Myasthenia gravis aggravated" (ongoing), notes: In Jan2020 and Feb2020, hospitalized two times; "Myasthenia gravis" (ongoing), notes: MG-ADL score: 18, acetylcholine (ACh) receptor binding antibody (Ab) positive, 27.2 (0.0-0.4) nmol, acetylcholine receptor blocking antibody positive (pos) 70 (0-26) %Striated Muscle Antibodies IgG reflex to titer titin antibody: 2.7 (0.0-0.45) IV Bulbar predominant; "Heaviness in leg" (ongoing); "Hypophonia" (ongoing), notes: hypophonic; "Constipation chronic" (ongoing); "Short-term memory impairment" (ongoing), notes: short-term memory; "Movement disorder NOS" (ongoing); "idiopathic polyneuropathy" (ongoing); "Autonomic imbalance" (ongoing); "Lower extremities weakness of" (ongoing), notes: both; "Gait instability" (ongoing), notes: impaired gait; "Pain" (ongoing); "Plasma exchange" (unspecified if ongoing), notes: For Generalized myasthenia gravis; "speech was slower" (unspecified if ongoing); "impaired mobility" (unspecified if ongoing). The patient's family history included: "Type 2 diabetes mellitus" (ongoing), notes: diabetes: father. Concomitant medication(s) included: ZYRTEC [CETIRIZINE HYDROCHLORIDE]; PROVIGIL [MODAFINIL], start date: 27Jan2022, stop date: 26Jul2022; SINEMET, start date: 11Apr2022; COREG, start date: 02Aug2021, stop date: 02Aug2022; KEFLEX [CEFALEXIN], start date: 13Jul2022, stop date: 20Jul2022; VITAMIN B 12 [CYANOCOBALAMIN]; PROSCAR; ROBINUL, start date: 08Apr2022; LINZESS; COZAAR, start date: 15Jul2021, stop date: 25Jul2022; GLUCOPHAGE, start date: 04Oct2021; SINGULAIR, start date: 03Mar2022; PRILOSEC [OMEPRAZOLE], start date: 03Mar2022; MESTINON, start date: 13Dec2021; VITAMIN C [ASCORBIC ACID]; ALFUZOSIN [ALFUZOSIN HYDROCHLORIDE]; ECOTRIN; TYLENOL; CA CMB NO.1. Past drug history included: Lyrica, reaction(s): "Adverse reaction"; Gabapentin, reaction(s): "Adverse reaction"; Ivig for Myasthenia gravis, reaction(s): "No adverse event", notes: Immunoglobulin I.V; Cellcept for Myasthenia gravis, reaction(s): "No adverse event ". Vaccination history included: pneumococcal polysaccharide, administration date: 01Jan2018, for Immunization; pneumococcal, administration date: 01Jan2015, for Immunization; tdap (Manufacturer: Sanofi Pasteur, Dose: 0.5ml, route: intramuscular, site: left deltoid, Lot: C5631AA), administration date: 12Sep2020, for Immunization, reaction(s): "No adverse event "; tdap, administration date: 20Nov2006, for Immunization, reaction(s): "No adverse event "; typhoid inactivated, administration date: 20Nov2006, for Immunization, reaction(s): "No adverse event "; typhoid inactivated (Lot: EO865, route: intramuscular), administration date: 09Dec2010, for Immunization, reaction(s): "No adverse event "; typhoid inactivated, administration date: 21Aug2000, for Immunization, reaction(s): "No adverse event "; yellow fever (Route: subcutaneous, Lot: UF794AA), administration date: 09Dec2010, for Immunization, reaction(s): "No adverse event"; yellow fever, administration date: 21Aug2000, for Immunization, reaction(s): "No adverse event"; cholera, administration date: 21Aug1988, for Immunization, reaction(s): "No adverse event"; hep a, administration date: 20Nov2006, for Immunization, reaction(s): "No adverse event"; hep a, administration date: 21Aug2000, for Immunization, reaction(s): "No adverse event"; hep b, administration date: 22Mar2007, for Immunization, reaction(s): "No adverse event"; hep b, administration date: 20Nov2006, for Immunization, reaction(s): "No adverse event"; hep b, administration date: 21Aug2000, for Immunization, reaction(s): "No adverse event"; ipv, administration date: 21Aug2000, for Immunization, reaction(s): "No adverse event"; meningococcal group b vaccine (Manufacturer: GlaxoSmithKline Dose: 0.5 ml route: intramuscular, site: right deltoid, 2 doses. Lot: ASXA60BA), administration date: 13Feb2020, for Immunization, reaction(s): "No adverse event"; meningococcal mcv4p (Manufacturer: GlaxoSmithKline Dose: 0.5 ml, route: intramuscular, site: right deltoid, Lot: U6576AA), administration date: 13Feb2020, for Immunization, reaction(s): "No adverse event"; meningococcal polysaccharide, administration date: 20Nov2006, for Immunization, reaction(s): "No adverse event"; meningococcal polysaccharide, administration date: 21Aug2000, for Immunization, reaction(s): "No adverse event"; bexsero (first dose, Serotype: Men B), administration date: 13Feb2020, for Immunization, reaction(s): "No adverse event"; bexsero (second dose, Serotype: Men B), administration date: 13Mar2020, for Immunization, reaction(s): "No adverse event"; menactra (Serotype: Men ACWY), administration date: 13Feb2020, for Immunization, reaction(s): "No adverse event"; Covid-19 vaccine (Dose 1, manufacturer: Unknown), for COVID-19 Immunization. The following information was reported: MYASTHENIA GRAVIS (medically significant) with onset Feb2021, outcome "recovering"; ASTHENIA (non-serious) with onset Jun2021, outcome "unknown", described as "Weaker"; FOOT FRACTURE (medically significant) with onset Nov2021, outcome "recovered", described as "Broken toe"; FALL (non-serious) with onset Apr2022, outcome "unknown", described as "Two falls"; PARAESTHESIA (non-serious), outcome "unknown", described as "Increasing tingling mostly in his feet"; CONFUSIONAL STATE (non-serious), outcome "unknown", described as "Confusion"; IMMUNISATION REACTION (non-serious), outcome "unknown", described as "Reaction to the second dose of the COVID vaccine"; ABNORMAL DREAMS (non-serious), outcome "unknown", described as "having more vivid dreams"; WEIGHT INCREASED (non-serious), outcome "unknown", described as "gained weight"; PHYSICAL DECONDITIONING (non-serious), outcome "unknown", described as "deconditioning"; HYPERSENSITIVITY (non-serious), outcome "unknown", described as "used suction since the last visit and thought it was more likely to be the result of excess secretions from allergies". The event "broken toe" required emergency room visit. The patient underwent the following laboratory tests and procedures: Blood pressure measurement: (unspecified date) 150/84; Haemoglobin: (Dec2020) 6.1, notes: high; Vitamin B12: (Dec2020) 170, notes: low; MG-ADL score: (unspecified date) 18; Antibody test: (unspecified date) positive; Antibody test (0.0-0.4): (unspecified date) 27.2 nmol; Antibody test (0-26): (unspecified date) 70 %; (unspecified date) positive; Autoantibody test (0.0-0.45): (unspecified date) 2.7, notes: IV Bulbar predominant. The action taken for eculizumab was unknown. Therapeutic measures were taken as a result of myasthenia gravis, foot fracture, paraesthesia. Additional information: This solicited case reported by a physician on 29Jul2022 concerns an elderly male patient of unspecified age (IDs). The patient was enrolled in Agency-sponsored program. The patient had no known allergies. On an unspecified date in Mar2020, the patient-initiated treatment with eculizumab (Soliris). He continued to have issues with fatigue as the day progressed, but had been on modafinil for about three months which had helped improve his energy and functioning. He continued eculizumab infusion (recently finished the 22nd infusion) and was tolerating it well. He denied any issues with swallow and ptosis.On an unspecified date, he experienced occasional changes in his speech towards the end of the day, but it was less frequent. His MG symptoms were controlled. He continued to have issues with sialorrhea and diplopia when reading towards the end of the day. He had continued with steroids (unspecified) and currently was on 2.5 mg, twice a day. He did not have any issues with worsening symptoms when weaning off prednisone. In the past two months, he experienced increasing tingling mostly in his feet (left feet greater than right feet) (Paraesthesia). He had tried topical agents for it in the past. As a result of the winter storm in Feb2021, he had missed a scheduled dose of eculizumab and his symptoms worsened (myasthenia gravis). The patient and his wife also thought he reacted to the second dose of the COVID vaccine (Immunisation reaction). He seemed to be weaker (asthenia) (episode of increased weakness in late June/early July) and suffered two falls (fall) in which he had difficulty picking himself up. He restarted in Mar2021 and since restarting his symptoms had improved. He experienced fatigue more in the evening. He used suction since the last visit and thought it was more likely to be the result of excess secretions from allergies. He was participating in physical and occupational therapy due to being too fatigued. He was dealing primarily with recurrent UTI and was in several courses of oral antibiotics. His neuropathy had improved with vitamin B12 supplements and the use of compression stocks. He might have some shortness of breath with activity but was mostly associated with deconditioning. He had more issues with gait Instability and falls (three falls in the last four months, two falls in May2022), especially in the evening. He has gained weight but was trying to lose weight to become more healthy. He had just completed his 53rd eculizumab Infusion (at the time of the report). His wife noted that when he did not receive the IV fluids with his infusion it seems he had more confusion (confusional state) and now that the IV fluids have been restarted on the infusions he seems to have less confusion. At times he got weaker towards the end of the day and white getting him to the bathroom or the bedroom. He noticed his speech was slower and he was having more issues with his short-term memory. Had a recent visit with the neurologist for his movement disorders who mentioned that it was a part of what is expected with Parkinson's. He suffered a broken toe (foot fracture) in Nov2021 which was reset in the ED and healed well. He is continuing to have worsened leg weakness and difficulty with balance which seemed to be due to both his history of Parkinson's and MG. This resulted in falls. He has been working with his movement disorder neurologist on Parkinson's management with the adjustment of the carbidopa, and levodopa dosing. However, when his dose was increased it was noted that he was having more vivid dreams. His last eculizumab infusion was 25Jul2022. The event of myasthenia gravis was assessed as medically significant by Alexion as this event is included in the important medical events list. The action taken with eculizumab and COVID-19 vaccine in response to the events was not reported. Corrective treatment for the events was not reported. The event of myasthenia gravis was resolving. The event foot fracture was resolved. The outcome of the other events was not reported. The reporter causality between the events and eculizumab was not reported. The reporter causality between the events and the COVID-19 vaccine was not reported.  The reporter's assessment of the causal relationship of "myasthenia gravis", "broken toe", "two falls", "increasing tingling mostly in his feet", "weaker", "confusion", "reaction to the second dose of the covid vaccine", "having more vivid dreams", "gained weight", "deconditioning" and "used suction since the last visit and thought it was more likely to be the result of excess secretions from allergies" with the suspect product(s) BNT162b2 was not provided at the time of this report. Since no determination has been received, the case is managed based on the company causality assessment.  Company comment: This case is a serious, medically confirmed, solicited report of event myasthenia gravis (MS): non-serious, medically confirmed events of fall, immunization reaction, foot fracture, confusional state, paraesthesia, and weakness. The events of paraesthesia and weakness are listed while the rest of the events are unlisted in the eculizumab CCDS. The listedness of events for the COVID-19 vaccine is unknown. The company considers the events of myasthenia gravis (worsening), fall, and weakness as not related to eculizumab; the events are more likely due to the underlying myasthenia gravis. Worsening symptoms occurred when the dose of prednisone was reduced. Foot fracture could be due to mechanical reasons or fall; hence not related to eculizumab. The event of confusional state could be due to dehydration and not related to eculizumab. Paraesthesia could be due to manifestations of diabetes mellitus and not related to eculizumab. Immunization reaction was due to the COVID-19 vaccine based on the temporal association to it; hence assessed as related to it and not related to eculizumab; the rest of the events are not related to the COVID-19 vaccine considering the lack of temporal plausibility.  No follow-up attempts are possible. No further information is expected.; Sender's Comments: As there is limited information in the case provided, the causal association between the reported events with the suspect drug BNT162B2 cannot be excluded. The case will be reassessed once new information is available. The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, Ethics Committees, and Investigators, as appropriate.