bluuebunny/crossref_metadata_2025 huggingface dataset:
Leflunomide-Associated Skin Ulceration
Authors: McCoy Christopher M
Published: June 2003

OBJECTIVE:

To report a case of skin ulceration as a result of treatment with leflunomide for rheumatoid arthritis.

CASE SUMMARY:

A 78-year-old white woman developed bilateral leg ulcers after 6 months of treatment with leflunomide for rheumatoid arthritis. A history of leg ulcers after methotrexate therapy had been documented. Serologic and diagnostic tests did not support an alternate process. Other medications prescribed were oral ethinyl estradiol 0.05 mg/d, felodipine 5 mg/d, and paroxetine 20 mg/d, for which no documented correlation with the skin breakdown could be made.

DISCUSSION:

This is the first published case describing a possible relationship between the use of the immunosuppressant agent leflunomide and skin ulceration.

CONCLUSIONS:

Skin breakdown and ulceration is a recognized adverse effect of drugs with immunosuppressant activity such as methotrexate. Leflunomide, a newer agent prescribed in the treatment of rheumatoid arthritis, may now be listed among the drugs in this category associated with this adverse drug effect.
Ciprofloxacin-Associated Hemolytic-Uremic Syndrome
Authors: Allan David S , Thompson Cheryl M , Barr Robert M , Clark William F , Chin-Yee Ian H
Published: June 2003

OBJECTIVE:

To report the first case of ciprofloxacin-associated hemolytic-uremic syndrome (HUS).

CASE SUMMARY:

A 53-year-old white man was treated with chemotherapy for acute lymphoblastic leukemia. Four weeks after initiation of treatment, he recovered his blood cell counts, but developed fever and was prescribed oral ciprofloxacin 500 mg twice daily. After 4 doses, he developed the typical features of HUS manifested by microangiopathic hemolytic anemia, oliguric renal failure, and thrombocytopenia. The medication was withdrawn, and he received 5 sessions of plasma exchange. He recovered completely and has normal renal function.

DISCUSSION:

Secondary HUS or its related syndrome, thrombotic thrombocytopenic purpura (TTP), is uncommon, but has been reported in association with cancer, chemotherapy, and a variety of medications. Our case represents a possible adverse drug reaction to ciprofloxacin according to the Naranjo probability scale. It is the first reported case of HUS associated with ciprofloxacin.

CONCLUSIONS:

Ciprofloxacin use was followed by HUS in our patient and was possibly causally related. Early detection, discontinuation of the offending medication, and treatment of HUS/TTP is critical.
Probable Metabolic Interaction of Doxifluridine with Phenytoin
Authors: Konishi Hiroki , Morita Kunihiko , Minouchi Tokuzo , Nakajima Masayuki , Matsuda Masayuki , Yamaji Akira
Published: June 2003

OBJECTIVE:

To report the marked elevation of the serum phenytoin concentration during treatment with antineoplastic agents.

CASE SUMMARY:

A 51-year-old Japanese woman, who was diagnosed with multiple brain metastatic tumors, was placed on oral phenytoin at a maintenance dose of 200 mg/d (3.8 mg/kg/d) to prevent seizures. The serum concentration of phenytoin was well controlled within the therapeutic range; no seizures occurred. Four months later, combination therapy with doxifluridine (5′-DFUR) 800 mg/d, cyclophosphamide 100 mg/d, and medroxyprogesterone acetate 800 mg/d was initiated because of further metastasis. Approximately 1 month after the start of concurrent treatment with the antineoplastic agents, the serum phenytoin concentration was elevated to fourfold of the original concentration. Staggering was observed at that time, but toxic symptoms gradually subsided with the decline in the serum phenytoin concentration after its withdrawal.

DISCUSSION:

A probable explanation for the marked elevation of serum phenytoin concentration is a reduction of the capacity of CYP2C-dependent phenytoin metabolism, and the antineoplastic agents could be involved in this event. The interaction of fluorouracil and phenytoin is known in clinical practice, and it is reported that the expression of hepatic CYP2C enzymes is depressed by exposure of rats to fluorouracil. 5′-DFUR, a prodrug of fluorouracil, was considered the likeliest candidate responsible for the interaction. This interaction was of clinical significance because of the great extent of changes in the serum phenytoin concentration.

CONCLUSIONS:

Clinicians should be aware of the elevation of serum phenytoin concentrations when phenytoin is given in combination with fluorouracil derivatives, including 5′-DFUR.
Priapism Associated with Zuclopenthixol
Authors: Salado Julio , Blázquez Antonio , Díaz-Simón Raquel , López-Muñoz Francisco , Alamo Cecilio , Rubio Gabriel
Published: June 2003

OBJECTIVE:

To present a single case of zuclopenthixol-induced priapism and a literature review.

CASE SUMMARY:

We report the case of a 31-year-old patient hospitalized due to behavioral alterations and treated with oral zuclopenthixol, an antipsychotic from the thioxanthene family, who developed an acute, painful erection.

DISCUSSION:

The occurrence of priapism in our patient was related to zuclopenthixol. This adverse reaction is reported for the first time in a patient not concomitantly treated with other drugs associated with the appearance of priapism. The capacity of zuclopenthixol to induce priapism is thought to be due to its antagonist activity on α-adrenergic receptors.

CONCLUSIONS:

Priapism is an uncommon but potentially serious adverse effect of zuclopenthixol that practitioners, as with many other antipsychotics, should be aware of.
24-Hour Ambulatory Blood Pressure Monitoring in Male Children Receiving Stimulant Therapy
Authors: Stowe Cindy D , Gardner Stephanie F , Gist Charles C , Schulz Eldon G , Wells Thomas G
Published: June 2003

OBJECTIVE:

To determine whether cardiac indices are altered as assessed by 24-hour ambulatory blood pressure monitoring (ABPM) in male children receiving either chronic methylphenidate or dextroamphetamine/levoamphetamine (Adderall) therapy.

METHODS:

Boys 7–11 years old who were receiving methylphenidate or Adderall for a minimum of 2 months were asked to participate. Subjects wore ambulatory blood pressure monitors for 24-hour periods both off and on stimulant therapy.

RESULTS:

Subjects (n = 17; 8 methylphenidate, 9 Adderall) were well matched. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate differed between off and on stimulant therapy (p < 0.05). DBP load calculated from ABPM reference data was increased significantly (9.0% ± 5.6% on and 4.8% ± 4.5% off therapy; p < 0.05) while subjects were taking Adderall. There was a trend toward a greater elevation in blood pressure load during awake hours and a more pronounced decrease during the asleep hours for periods on compared with off-stimulant therapy. This trend resulted in significant (p < 0.05) nocturnal dipping on-stimulant phases compared with off-stimulant therapy for both SBP and DBP (Adderall) and SBP (methylphenidate). Two subjects (1 Adderall, 1 methylphenidate) met the criteria to be considered hypertensive based both on mean awake and 24-hour blood pressure load assessments during their on-treatment period. One additional subject receiving Adderall therapy met the criteria to be considered hypertensive based on blood pressure load criteria while off therapy only. Positive correlation coefficients (p < 0.05) were found when comparing stimulant dose (mg/kg) with the percent change of mean SBP, DBP, and heart rate between off and on therapy (r = 0.56, 0.61, and 0.58, respectively).

CONCLUSIONS:

These preliminary data suggest that blood pressure and heart rate appear to be altered in male patients while receiving stimulant therapy for attention-deficit hyperactivity disorder. Blood pressure and heart rate screening and monitoring during stimulant therapy to determine whether alterations become clinically significant is encouraged.
Effect of Therapeutic Class on Counseling in Community Pharmacies
Authors: Vainio Kirsti K , Airaksinen Marja SA , Hyykky Tarja T , Enlund K Hannes
Published: June 2003

OBJECTIVE:

To assess the effect and importance of the therapeutic class of a drug as a determinant for verbal counseling by community pharmacists.

METHODS:

Direct external observations (n = 1431) of pharmacist—customer interactions at the point of delivery of prescription medicines were conducted in 7 community pharmacies in Finland. Trained observers noted whether the pharmacist provided information on directions for use, mode of action, and adverse effects. To examine factors associated with counseling, a multiple logistic regression analysis was constructed, with the dependent variable being counseling of any of the 3 observed topics. In addition to therapeutic class, other independent variables were the pharmacy; pharmacist's age, gender, and degree; and the customer's age, gender, previous use of medicine, and question asking.

RESULTS:

Provision of counseling differed significantly according to therapeutic classes. Counseling on any of the 3 observed topics was most likely to be provided for customers with antibiotics (80%) and least likely for customers with gynecologic preparations (18%). Differences between therapeutic classes remained statistically significant when the effects of the other variables were controlled for. Other significant predictors for any verbal counseling were the pharmacy, customer's previous use of the medicine, and question asking.

CONCLUSIONS:

Therapeutic class is an important variable that should be included in further studies and considered when comparing studies on patient counseling in community pharmacies.
Valganciclovir: An Advance in Cytomegalovirus Therapeutics
Authors: Cocohoba Jennifer M , McNicholl Ian R
Published: June 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, and preliminary clinical data for valganciclovir, a new oral agent for the therapy of cytomegalovirus (CMV) retinitis.

DATA SOURCES:

Relevant literature was extracted via MEDLINE/PUBMED and searchable abstracts from infectious diseases conferences covering the period from January 1990 to April 2002. Tertiary references provided background information.

DATA SYNTHESIS:

Current standard treatment for CMV retinitis consists of intravenous therapy, intraocular implant, and intraocular injection. The low bioavailability of oral ganciclovir restricts its use to prophylaxis and maintenance treatment. Oral valganciclovir, recently approved for both induction and maintenance therapy of CMV retinitis, may fill a niche for this disease.

CONCLUSIONS:

Although only 1 clinical study has been published for valganciclovir, its favorable pharmacokinetic profile, encouraging preliminary efficacy data, ease of administration, and lack of potential catheter-related complications make it a favorable option for the treatment of CMV retinitis in HIV-positive patients.
Anakinra Treatment of Patients with Rheumatoid Arthritis
Authors: Calabrese Leonard H
Published: June 2003

OBJECTIVE:

To summarize the safety data arising from clinical trials of anakinra, a human recombinant form of interleukin-1 receptor antagonist (IL-1Ra) developed for the treatment of rheumatoid arthritis (RA).

DATA SOURCES:

Primary articles and abstracts identified through the National Library of Medicine's PubMed database (1982–2001) and secondary sources.

STUDY SELECTION AND DATA EXTRACTION:

All the articles and abstracts identified from the data sources were evaluated and all information deemed relevant was included in this review.

DATA SYNTHESIS:

Overall, anakinra was shown in 4 trials to be efficacious as monotherapy or combination therapy, compared with placebo, for the treatment of active RA. The magnitude of clinical improvement tended to increase with increasing doses of anakinra. In monotherapy trials, the primary adverse event was injection-site reactions, which usually were mild and transient. In combination therapy (anakinra plus methotrexate), the frequency and severity of adverse events were similar to those seen in the monotherapy trials.

CONCLUSIONS:

The use of anakinra in patients with RA inhibits disease activity with a favorable tolerability profile.
Fomepizole as an Antidote for Ethylene Glycol Poisoning
Authors: Battistella Marisa
Published: June 2003

OBJECTIVE:

To assess the use of fomepizole in the treatment of ethylene glycol poisoning in the absence of hemodialysis.

DATA SOURCES:

A MEDLINE search (1966–May 2001) of English-language literature pertaining to the use of fomepizole in ethylene glycol poisoning was performed. Key search terms included fomepizole, ethylene glycol poisoning, and hemodialysis. References cited in those articles were also evaluated.

DATA SYNTHESIS:

Results from a number of case reports and a prospective trial suggest that fomepizole is a safe and effective antidote in the treatment of ethylene glycol poisoning.

CONCLUSIONS:

Case reports and 1 prospective trial have shown that, in the absence of both renal dysfunction and significant metabolic acidosis, the use of fomepizole should obviate the need for hemodialysis. However, the decision to add hemodialysis in the treatment of ethylene glycol poisoning based on plasma ethylene glycol concentrations is still debatable. A randomized, controlled trial is needed to determine the exact criteria for adding hemodialysis.
Clinical Implications of Endotoxin Concentrations in Vaccines
Authors: Geier David A , Geier Mark R
Published: June 2003

BACKGROUND:

A previous study suggested that high concentrations of endotoxin may be present in whole-cell diphtheria/tetanus/pertussis (DTP) vaccine, and the scientific literature contains many studies examining the reactivity of whole-cell DTP vaccine. The medical and scientific communities have previously reported that the presence of endotoxin in commercial vaccines may have negative effects on vaccine recipients.

OBJECTIVE:

To determine the endotoxin concentrations in whole-cell DTP, acellular DTP (DTaP), and DT vaccines and determine the clinical experience with each vaccine.

METHODS:

To study the endotoxin concentrations in vaccines, the Limulus amebocyte lysate (LAL) assay was used. The vaccines analyzed with the LAL assay were whole-cell DTP vaccine lots manufactured by Connaught, Lederle, the Michigan and Massachusetts Departments of Health, and Wyeth; DTaP vaccine lots manufactured by Merieux and Takeda; and DT vaccine lots manufactured by Wyeth and Lederle. The incidence of adverse reactions following whole-cell DTP, DTaP, and DT vaccines were determined based on analysis of the Vaccine Adverse Events Reporting System (VAERS) database.

RESULTS:

The results of the LAL assay showed that whole-cell DTP vaccines contained considerably more endotoxin than either DTaP or DT vaccines. The VAERS showed that statistically significantly more adverse reactions were associated with whole-cell DTP vaccine than DTaP or DT vaccines.

CONCLUSIONS:

This analysis confirmed higher concentrations of endotoxin in whole-cell DTP vaccines compared with DTaP or DT vaccines. As high concentrations of endotoxin may be correlated with a higher incidence of adverse events, the switch from whole-cell DTP to DTaP for routine vaccinations in the US seems well justified.
Early Statin Therapy for Acute Coronary Syndromes
Authors: de Denus Simon , Spinler Sarah A
Published: June 2003

OBJECTIVE:

To review the clinical benefit of statins in the early management of acute coronary syndromes (ACSs) and their possible mechanisms of benefit.

DATA SOURCES:

A MEDLINE search (1966–September 2001) was conducted using the following terms: pravastatin, lovastatin, simvastatin, atorvastatin, cerivastatin, fluvastatin, statins, hydroxymethylglutaryl coenzyme A reductase inhibitor, acute coronary syndromes, unstable angina, and myocardial infarction. Pertinent articles referenced in these publications were also reviewed.

STUDY SELECTION AND DATA EXTRACTION:

French- and English-language human and animal studies were selected and analyzed.

DATA SYNTHESIS:

In addition to their lipid-lowering properties, statins produce several nonlipid-related properties. These pleiotropic properties include improved endothelial function, reduction of inflammation at the site of the atherosclerotic plaque, inhibition of platelet aggregation, and anticoagulant effects, all of which may result in clinical benefit during ACSs. Preliminary studies and retrospective analyses of large clinical trials support the hypothesis that statins may be of benefit in ACSs. A recently published randomized, double-blind, multicenter trial evaluated the clinical impact of high-dose atorvastatin in patients with ACSs. Use of atorvastatin resulted in a decrease in a combined endpoint of cardiovascular events. Furthermore, initiation of statin therapy during hospitalization improves long-term compliance and may significantly improve clinical outcome.

CONCLUSIONS:

Early use of statins in ACSs appears to decrease cardiovascular events. We believe statin therapy should be initiated early (at the latest before hospital discharge) in all patients who have been hospitalized for ACSs. Ongoing studies will clarify the benefit of these agents in ACSs, the importance of their nonlipid-lowering properties, and the optimal cholesterol-target concentrations.
Darbepoetin Alfa: A Novel Erythropoiesis-Stimulating Protein
Authors: Joy Melanie S
Published: June 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of darbepoetin alfa.

DATA SOURCES:

Pertinent references were identified by a MEDLINE search (1995–January 2001) of the medical literature, review of English-language literature and references of these articles, product information, and abstracts from professional meetings.

STUDY SELECTION:

Clinical efficacy data were gathered from all available trial data citing darbepoetin alfa. Additional information concerning pharmacology, pharmacokinetics, and safety was also reviewed.

DATA SYNTHESIS:

Darbepoetin alfa is a new erythropoiesis-stimulating protein with a threefold longer half-life than recombinant human erythropoietin (r-HuEPO). Darbepoetin alfa is approved for intravenous and subcutaneous administration in patients requiring and not requiring dialysis. Clinical studies in patients with chronic kidney disease (CKD) have shown darbepoetin alfa to be equivalent to r-HuEPO in terms of increases in hemoglobin concentration, percentage of patients obtaining target hemoglobin, and average time to reach target hemoglobin concentration. Trials are currently ongoing in patients receiving cancer chemotherapy. The adverse event profile appears to be similar between the 2 agents.

CONCLUSIONS:

The equivalent efficacy and safety profile, as well as the longer half-life, may make darbepoetin alfa an attractive alternative to r-HuEPO in patients with CKD. Since these patients need to receive r-HuEPO 1–3 × weekly at the expense of increased healthcare utilization to improve their hemoglobin, agents such as darbepoetin alfa, with longer durations of action, may reduce healthcare expenses. In addition, enhanced patient compliance may be realized with once-weekly or once every-other-week administration.
Orlistat Use in Type 2 Diabetes
Authors: Snider Laura J , Malone Margaret
Published: June 2003

OBJECTIVE:

To review the use of orlistat in type 2 diabetes.

DATA SOURCES:

A MEDLINE search of the English-language literature (1990–August 2001) was performed using the key terms orlistat, obesity, glucose, and diabetes.

DATA EXTRACTION:

All articles pertaining to orlistat were considered for inclusion, with emphasis placed on randomized, placebo-controlled, double-blind clinical trials.

DATA SYNTHESIS:

In April 1999, orlistat was approved by the Food and Drug Administration for the treatment of obesity. Of 13 randomized, placebo-controlled studies, only 2 reported specific data in individuals with type 2 diabetes. Both reported significant weight reduction and improved glycemic control over placebo.

CONCLUSIONS:

Since weight loss is a difficult goal to achieve in patients with type 2 diabetes, orlistat can be a safe, effective addition to a multidisciplinary approach.
Anthrax: Safe Treatment for Children
Authors: Benavides Sandra , Nahata Milap C
Published: June 2003

Information regarding the treatment of anthrax infection is scarce in adults and is even more limited in children. Children, however, may be at a greater risk for developing an infection and systemic disease if exposed to anthrax than adults. The Centers for Disease Control and Prevention (CDC) recommends the use of doxycycline or ciprofloxacin for prophylaxis and treatment in children. Doxycycline currently is not indicated for use in children <8 years old, due to staining of teeth and inhibition of bone growth associated with tetracyclines. Doxycycline, however, may have less adverse effect on teeth than its precursors. Ciprofloxacin has a pediatric indication only when a child is potentially exposed to inhaled anthrax. Ciprofloxacin is contraindicated in pediatric patients because fluoroquinolones were shown to cause cartilage toxicity in immature animals. Although children of various ages have received ciprofloxacin, there are few reports of cartilage toxicity. Because anthrax is a potentially fatal infection, the benefits to using these antibiotics greatly outweigh the risks. Therefore, the use of these antibiotics in children can be recommended, despite the lack of adequate efficacy and safety studies in pediatric patients with anthrax.
Factors Affecting Warfarin Therapy following Cardiac Valve Surgery
Authors: Lee Juyeun , Lee Byungkoo , Kim Kibong , Ahn Hyuk , Suh Okkyung , Lee Myungkoo , Shin Wangyoon
Published: June 2003

OBJECTIVE:

To determine the factors that affect the initial response to warfarin therapy in Korean patients after cardiac valve surgery.

METHODS:

A retrospective analysis of 127 patients who had undergone cardiac valve surgery at Seoul National University Hospital was performed. On the first day, most patients received warfarin 5 mg, while some received an individualized warfarin dose according to their physician's decision. Doses to be given on the following days were determined based on daily international normalized ratio (INR) and the previous doses. To measure warfarin sensitivity, the warfarin dose index (WDI), defined as the INR divided by the mean warfarin dose administered during the preceding 3 days, was introduced. The effects of age, gender, weight, serum albumin concentration, baseline INR, cardiopulmonary bypass time, and concurrent administration of amiodarone were evaluated.

RESULTS:

The patients' weight, initial serum albumin concentration, and baseline INR value influenced their initial response to warfarin. The initial WDI correlated negatively with the initial serum albumin concentration (p < 0.001) and body weight (p < 0.05) and positively with the baseline INR (p < 0.01). The initial WDI of the patients taking amiodarone was significantly higher (mean ± SD 0.74 ± 0.34) than that of patients without amiodarone (0.46 ± 0.22) (p < 0.001). Maintenance doses correlated negatively with the initial warfarin response (p < 0.001) and positively with body weight (p = 0.053).

CONCLUSIONS:

The factors associated with an increased initial warfarin response in patients after cardiac valve surgery were high baseline INR, low postoperative serum albumin concentration, and concurrent administration of amiodarone. Thus, patients with any of these factors should receive a smaller initial warfarin dose. Also, to predict the warfarin maintenance dose from the initial response, the effect of transient changes in the sensitivity to warfarin during the initial period should be considered.
Efavirenz-Associated QT Prolongation and Torsade de Pointes Arrhythmia
Authors: Castillo Ricardo , Pedalino Ronald P , El-Sherif Nabil , Turitto Gioia
Published: June 2003

OBJECTIVE:

To report a case of acquired long QT syndrome that, after exclusion of all other possible causes, was probably related to therapy with efavirenz, a novel nonnucleoside reverse transcriptase inhibitor.

CASE SUMMARY:

This patient presented with recurrent syncope and polymorphic ventricular tachycardia, which was treated with overdrive ventricular pacing and was eliminated by discontinuation of the offending drug.

DISCUSSION:

This is the first reported case of QT prolongation and severe ventricular arrhythmia associated with the use of efavirenz. The temporal relationship between the initiation of treatment and the onset of electrocardiographic abnormalities, the absence of other apparent precipitating factors, as well as the normalization of QT interval and the resolution of the arrhythmia after discontinuation of the drug, strongly suggest a causal relationship between efavirenz and this adverse clinical event.

CONCLUSIONS:

Our case shows that any new pharmaceutical compound introduced in clinical practice may potentially result in QT prolongation and life-threatening arrhythmia.
Effect of Enoxaparin on Homocysteine Concentration in Warfarin-Treated Patients
Authors: Haviv Yael , Lubetsky Aaron , Sela Ben-Ami , Ezra David , Olchovsky David
Published: June 2003

BACKGROUND:

Elevated plasma total homocysteine (tHcy) concentration is an emerging independent risk factor for hypercoagulability states and cardiovascular diseases. Many disease states and various drug treatment regimens are known to affect plasma tHcy concentration.

OBJECTIVE:

To examine the effect of short-term treatment with the low-molecular-weight heparin enoxaparin on plasma tHcy concentrations.

METHODS:

A prospective study was conducted in an outpatient anticoagulation clinic set in a tertiary care referral medical center. Subjects included twenty-four consecutive patients treated with warfarin who were scheduled for short-term enoxaparin treatment. Fasting plasma tHcy concentrations were measured before and after 3 days of enoxaparin treatment in patients who began short-term therapy with enoxaparin because of temporary inadequate anticoagulation (international normalized ratio <1.5). The main outcome measures were the difference in tHcy concentration between baseline and after enoxaparin treatment.

RESULTS:

tHcy plasma concentrations decreased in most patients (n = 21), did not change in 2, and increased in 1 patient after 3 days of enoxaparin treatment. The decline of tHcy was statistically significant: from 9.8 ± 3.4 to 7.6 ± 2.6 μmol/L (mean ± SD; p < 0.005). This decline was more prominent in patients with baseline tHcy plasma concentrations above the normal range compared with patients with normal baseline concentrations. Six patients in whom a third sample was obtained 15–30 days after the last enoxaparin injection developed decreased mean tHcy plasma concentrations: from 9.1 ± 3.0 μmol/L at baseline to 6.4 ± 2.0 μmol/L on day 3 and further to 5.7 ± 1.8 μmol/L on days 15–30. No relation was found between age, gender, treatment indication, and average weekly dose of warfarin to the presence or magnitude of tHcy plasma concentration decline.

CONCLUSIONS:

Short-term treatment with enoxaparin reduces plasma tHcy concentrations. Further studies are needed to clarify the mechanism and the clinical significance of enoxaparin's effect.
Low-Molecular-Weight Heparins and Thrombocytosis
Authors: Liautard Christine , Nunes Ana-Maria Correa , Vial Thierry , Chatillon Fabienne , Guy Claire , Ollagnier Michel , Descotes Jacques
Published: June 2003

BACKGROUND:

A possible association between low-molecular-weight heparins (LMWHs) and thrombocytosis was suspected from spontaneous reports to the French Pharmacovigilance System. This association is not mentioned in LMWH's summary of product characteristics.

METHODS:

All case records in the French Pharmacovigilance database were reanalyzed for relevance and causality, and the case/noncase approach was used including reports of thrombocytosis as cases and all other reports as noncases.

RESULTS:

Fifty-one patients treated with LMWHs had platelet counts >500 × 103/mm3. All patients were asymptomatic, and 1 had a positive rechallenge. There were 143 cases of thrombocytosis among the 174 213 reports in the database, with 61 of 4644 involving LMWHs. The calculated relative reporting ratio is 27.5 (p < 0.0001; 95% CI 19.5 to 38.9).

CONCLUSIONS:

There is a highly significant association of thrombocytosis reported with LMWH treatment.
Serum Quinidine Concentrations and Effect on QT Dispersion and Interval
Authors: Mathis A Scott , Gandhi Ashesh J
Published: June 2003

OBJECTIVE:

To establish a relationship between serum quinidine concentrations (SQCs) and QT interval dispersion, compared with corresponding QT intervals, in order to identify a reason why many reports describe torsade de pointes as occurring at subtherapeutic concentrations.

DESIGN:

Retrospective study.

SETTING:

University teaching hospital.

PARTICIPANTS:

Eleven patients with atrial arrhythmias managed with quinidine therapy.

MAIN OUTCOME MEASURES:

Patients with subtherapeutic (<2 μg/mL) and therapeutic (2–5 μg/mL) SQCs with corresponding 12-lead electrocardiograms (ECGs) (25 mm/sec) and baseline ECG were evaluated for QT interval dispersion, calculated as the maximum minus the minimum QT interval on the 12-lead ECG.

RESULTS:

Mean ± SD subtherapeutic and therapeutic SQCs were 1.48 ± 0.39 μg/mL and 3.78 ± 0.88 μg/mL (p < 0.001). Baseline values for QT/QTc intervals were 376.4 ± 59.2/429.5 ± 57.3 msec. At subtherapeutic and therapeutic SQCs, mean QT/QTc intervals were 403.6 ± 59.9/450.5 ± 38.5 msec and 439.1 ± 48.9/472.4 ± 44.6 msec, respectively. Mean QT dispersion was 47 ± 16.2 msec at baseline, 98.2 ± 27.5 msec at subtherapeutic SQC, and 70.9 ± 33.9 msec at therapeutic SQCs (p = 0.001 for overall analysis; p < 0.001 for baseline vs. subtherapeutic concentrations; p = NS for therapeutic vs. subtherapeutic in post hoc comparison).

CONCLUSIONS:

Despite QT interval lengthening with increasing SQCs, QT dispersion was numerically greatest at subtherapeutic SQCs. Further study is required to determine the value of QT dispersion as a tool for identifying proarrhythmic risk with drugs that prolong the QT interval.
Nephrotoxicity and Purpura Associated with Levofloxacin
Authors: Famularo Giuseppe , De Simone Claudio
Published: June 2003

OBJECTIVE:

To report a patient with lung cancer and idiopathic myelofibrosis with myeloid metaplasia who developed purpura and acute renal failure while receiving levofloxacin, and review the existing literature on quinolone nephrotoxicity.

CASE SUMMARY:

A 73-year-old white man, with a medical history of non-small-cell lung cancer and idiopathic myelofibrosis with myeloid metaplasia, was prescribed levofloxacin because of a lower urinary tract infection. Three days later, he presented with palpable purpura and erythematous skin lesions over the lower limbs and trunk, with a markedly reduced urinary output. Serum creatinine and urea nitrogen were 6.4 and 190 mg/dL, respectively. Levofloxacin was discontinued, and prednisone, furosemide, and intravenous fluids were given. The patient fully recovered over the ensuing 4 weeks.

CONCLUSIONS:

Nephrotoxicity associated with levofloxacin is uncommon. Allergic interstitial nephritis or vasculitis is believed to be the underlying pathologic process. Definitive diagnosis requires performance of renal biopsy, although this is not always feasible. In this case, a return of renal function to normal, with the disappearance of purpura following the discontinuation of levofloxacin and corticosteroid treatment, supports the presumptive diagnosis of a hypersensitivity reaction to levofloxacin.
Intrathecal Morphine after Cardiac Surgery
Authors: Boulanger Aline , Perreault Sylvie , Choinière Manon , Priéto Ignacio , Lavoie Claire , Laflamme Claude
Published: June 2003

OBJECTIVE:

To assess whether intrathecal (IT) analgesia facilitates early extubation and provides superior pain control after cardiac surgery compared with patient-controlled analgesia (PCA) or nurse-administered SC injections.

METHODS:

Sixty-two patients undergoing elective cardiac surgery participated in this prospective, randomized, partly-blinded study. Perioperative care was standardized, and patients were assigned to receive IT morphine (ITM group) followed by PCA, IT placebo (ITP group) followed by PCA, or SC injections of morphine every 4 hours as needed (SC group). Rating scales and questionnaires were used to assess clinical outcomes.

RESULTS:

ITM did not favor earlier extubation, and there was even a tendency for longer extubation × in the ITM group compared with the ITP and SC groups. Pain scores, adverse effects, postoperative recovery, and patient satisfaction were also comparable in the 3 groups.

CONCLUSIONS:

Considering that the administration of IT morphine is more costly and can be riskier than conventional analgesic regimens, we conclude that its use is not indicated in patients undergoing cardiac surgery if early extubation is planned.
Why Aren't Lower, Effective, OTC Doses Available Earlier by Prescription?
Authors: Cohen Jay S
Published: June 2003

BACKGROUND

Many popular oral over-the-counter (OTC) drugs were originally available only by prescription, but not at the low doses contained in their OTC counterparts. Yet, if OTC doses are effective for treating mild symptoms, why weren't these low, often safer doses made available at least by prescription when the drugs were first approved?

OBJECTIVE

To examine issues surrounding the delayed approval of OTC doses by the Food and Drug Administration (FDA).

METHODS

Information reviewed included package inserts, data obtained from manufacturers, and articles published in MEDLINE (1966 to December 2001). Medications examined included presently available and potentially approved OTC antiinflammatory, gastrointestinal, and antihistamine drugs.

RESULTS

Considerable data demonstrate the effectiveness of ibuprofen, naproxen, ranitidine, famotidine, nizatidine, diphenhydramine, and clemastine at OTC doses. Published studies also show the effectiveness of celecoxib, omeprazole, and fexofenadine at doses 33–50% lower than currently recommended for prescription use.

CONCLUSIONS

OTC doses are effective for many patients with mild symptoms and for some with serious symptoms. However, OTC-like doses are usually not offered when drugs are approved for prescription use because new drugs are usually studied in patients with serious conditions requiring higher doses; manufacturers and the FDA seem to prefer a middle-dose approach; >75% of subjects in premarketing dose studies are male; and averaging the responses of study subjects may obscure a wide range of interindividual variation in drug response. Simplistic dosage guidelines make therapeutic decisions easier. Because dose-related adverse effects frequently diminish quality-of-life and reduce adherence, the early availability of OTC-like doses, at least by prescription, would allow healthcare professionals greater flexibility in matching medication doses to patients’ widely differing needs.
Nefopam Abuse
Authors: Villier Céline , Mallaret Michel P
Published: June 2003

OBJECTIVE:

To report 3 patients who abused nefopam, a central analgesic that inhibits serotonin, norepinephrine, and dopamine reuptake.

CASE SUMMARIES: CASE 1:

A 42-year-old white woman with migraines started nefopam therapy about 10 years ago. She now obtains nefopam by prescription forgery and self-administers intramuscular nefopam 300 mg/d. She experiences anticholinergic effects of nefopam and, when attempting withdrawal, depressive symptoms. CASE 2: A 40-year-old white woman with osteoporosis has injected 120 mg of nefopam intramuscularly daily for several years. When she tried to increase doses due to worsening of her symptoms, she experienced tremor, involuntary movements, and dry mouth, and became aggressive. She then resumed the initial doses. She now reports symptoms of depression when attempting withdrawal. CASE 3: A 33-year-old white man, with a history of alcohol and benzodiazepine dependence and ileostomy, and an implanted drug delivery system, has been prescribed nefopam. Fifteen days after therapy was initiated, his daily consumption was 840 mg/d, and further increased to 1840 mg/d. He experienced violent behavior, agitation, facial dysesthesia and myoclonus, tremor of fingers, and sweating. He did not attempt withdrawal.

DISCUSSION:

The patients described above are drug-dependent according to the Diagnostic and Statistical Manual, 4th Edition. All patients developed a pharmacodynamic tolerance phenomenon, which can develop rapidly. Violent behavior, tremor after massive intake, and depressive symptoms during withdrawal are similar to those reported with psychostimulant abuse.

CONCLUSIONS:

When abused, nefopam has primarily psychostimulant-like effects, which are probably linked to its dopamine reuptake inhibition properties.
Meningococcal Vaccine Use in College Students
Authors: Kelleher Julia A , Raebel Marsha A
Published: June 2003

OBJECTIVE:

To discuss the role of meningococcal vaccine in prevention of meningococcal disease.

DATA SOURCES:

A MEDLINE search (1966–June 2001) was performed to identify key literature. Search terms included, but were not limited to, meningococcal vaccines, meningococcal meningitis, meningococcal infection, and meningococcus. The search was limited to English-language literature and references dealing with humans. The MEDLINE search was supplemented by a hand search of various bibliographies.

DATA SYNTHESIS:

The impact of meningococcal disease has caused national and regional organizations to develop recommendations for use of meningococcal vaccine. Even though the meningococcal vaccine can provide benefit, limitations exist. The available vaccine does not cover all meningococcal strains and is not useful in all age groups. The appropriate target groups for prevention of disease through vaccination have been difficult to determine; vaccine use in college students is especially controversial.

CONCLUSIONS:

Although a meningococcal vaccine is available, meningococcus causes significant morbidity and mortality. Controversy exists over the meningococcal vaccine and its use. Students entering college who will be living in dormitories should be informed of the increased risk of meningococcal disease and be offered vaccination.
Epidemiology and Toxicity of Pediatric Guanfacine Exposures
Authors: McGrath Jean C , Klein-Schwartz Wendy
Published: June 2003

OBJECTIVE:

To examine the epidemiology and toxicity of guanfacine exposures in children and adolescents reported to poison control centers.

METHODS:

Guanfacine exposures reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System from 1993 to 1999 in children and adolescents <19 years of age were analyzed.

RESULTS:

There were 870 cases that met the inclusion criteria: 478 (54.9%) were children <6 years old, 304 (34.9%) were 6–12 years old, and 88 (10.1%) were adolescents 13–18 years old. The number of cases increased eight-fold over the 7-year period, with the largest increase in children <13 years of age. Analysis showed 29.7% of exposures were managed on site (non-healthcare facility) and 68.3% were managed in a healthcare facility. There were no symptoms in 546 (62.8%) children. In 324 symptomatic children, the most common symptoms were drowsiness/lethargy (76.8%), bradycardia (30.0%), and hypotension (25.8%). The majority of cases were acute (77.5%), 182 (20.9%) were acute-on-chronic, and 14 (1.6%) were chronic. Children aged 6–12 years represented the majority of the acute-on-chronic and chronic exposures with (n = 118). Overall, there were 195 (22.4%) exposures coded as minor, 121 (13.9%) as moderate, and 8 (0.9%) as major effects.

CONCLUSIONS:

These data demonstrated a trend of increasing numbers of guanfacine exposures annually. Although the majority of children experienced minimal or no toxicity, serious toxicity can occur.
Tenfold Medication Dose Prescribing Errors
Authors: Lesar Timothy S
Published: June 2003

BACKGROUND:

Tenfold errors in medication dosing continue to occur despite being a well-recognized risk, particularly to pediatric patients. Few systematic evaluations of the characteristics and causes of tenfold medication dosage prescribing errors have been performed.

OBJECTIVE:

To identify and quantify the characteristics of tenfold medication dosage prescribing errors.

DESIGN:

Evaluation of 200 consecutively detected medication orders with tenfold errors in dosing in a 631-bed tertiary-care teaching hospital.

MAIN OUTCOME MEASURES:

Type, frequency, characteristics, causes, enabling factors, and potential for adverse effects of tenfold medication dosage prescribing errors.

RESULTS:

Two hundred cases of tenfold prescribing errors were detected over an 18-month period. Overdoses were prescribed in 61% of the cases and underdoses in 39% of the cases. Ninety (45%) of the errors were rated as potentially serious or severe; 19.5% of the errors ocurred in pediatric patients. Levothyroxine accounted for 19% of all errors. As a class, antimicrobials, cardiovascular agents, and central nervous system agents each accounted for ≥15% of errors. Errors were associated with multiple zeroes in the dose (45%), use of equations or calculations to determine dose (27% total cases, 92.3% of pediatric cases), dose amount less than 1 (25%), and expression of measure conversion (23%). The tenfold errors were produced by a misplaced decimal point in 87 cases (43.5%), adding an extra zero in 63 cases (31.5%), and omitting a zero in 50 cases (25%). Factors identified as enabling a tenfold error to be carried out as ordered were a wide dose range for the drug (76.5%), medication ordered and able to be given by injection (42%), ability to give ordered dose as ≤5 solid oral dosage forms (36%), and availability of an oral liquid dose form (15%).

CONCLUSIONS:

Prescribing of tenfold medication dose errors is common and is associated with identifiable risk factors. Implementing commonly recommended medication safety processes are likely to reduce risk to patients from such errors. This information should be considered in the development of strategies to prevent adverse patient outcomes resulting from such errors.
Oral Antithrombotic Use Among Myocardial Infarction Patients
Authors: van der Elst Menno E , Cisneros-Gonzalez Nelly , de Blaey Cornelis J , Buurma Henk , de Boer Anthonius
Published: June 2003

OBJECTIVE

To examine the use of oral antithrombotics (i.e., antiplatelet agents, oral anticoagulants) after myocardial infarction (MI) in the Netherlands from 1988 to 1998.

METHODS

Retrospective follow-up of 3800 patients with MI, using data from the PHARMO Record Linkage System.

RESULTS

From 1988 to 1998, oral antithrombotic treatment increased significantly from 54.0% to 88.9%. In 1998, only 75.8% of patients who experienced a MI in the late 1980s received oral antithrombotic treatment compared with 94.4% of those who experienced a recent MI.

CONCLUSIONS

Oral antithrombotics were considerably underused in patients with a past history of MI. Therefore, these patients should be reviewed for antithrombotic therapy to assess whether their failure to use oral antithrombotics was right or wrong, and whether treatment should be initiated if possible.
Quetiapine Therapy for Posttraumatic Stress Disorder
Authors: Sattar S Pirzada , Ucci Bernadette , Grant Kathleen , Bhatia Subhash C , Petty Frederick
Published: June 2003

OBJECTIVE:

To report a case of improvement in posttraumatic stress disorder (PTSD) after adjunctive therapy with quetiapine.

CASE SUMMARY:

A 49-year-old white man witnessed a traumatic event and experienced severe PTSD. He was started on paroxetine, with increases in dosage and no significant improvement. Quetiapine was added to his regimen, with increased doses resulting in improvement of PTSD symptoms, both clinically and as measured on the Hamilton-D rating scale for depression and the clinician-administered PTSD screen.

DISCUSSION:

This is the first case published in the English language literature describing improvement in PTSD symptoms after treatment with quetiapine. There are several treatment options for PTSD, but some severe cases may require treatment with antipsychotic medications. Because of the lower risks of serious adverse effects, the newer atypical antipsychotics are much safer than the older antipsychotics. Although use of risperidone and olanzapine in the successful treatment of PTSD has been reported in the literature, there are no reports of quetiapine use in this clinical condition.

CONCLUSIONS:

Quetiapine appeared to improve clinical signs and symptoms of PTSD in this patient. It may be a treatment option in other severe cases of PTSD.
Cardiotoxicity following Bupropion Overdose
Authors: Druteika Deon , Zed Peter J
Published: June 2003

OBJECTIVE:

To determine whether bupropion overdose has been associated with cardiovascular toxicity.

DATA SOURCES:

MEDLINE (1966–January 2002), EMBASE (1980–January 2002), Current Contents (January 2002), and PubMed (January 2002) databases for English-language human reports. Search terms included bupropion, overdose (drug), intoxication, poisoning, and acute ingestion.

DATA SYNTHESIS:

Articles describing toxicity following bupropion overdose were evaluated independently by both authors to identify cases of cardiotoxicity.

RESULTS:

Thirteen articles describing bupropion overdose in 116 patients were identified. Only 3 patients exhibited cardiotoxicity following acute ingestion; 2 of these patients also ingested other medications. All 3 patients experienced tachycardia and conduction delays (widened QRS complex and/or prolonged QTc interval), but none of these delays progressed to a life-threatening arrhythmia. All patients recovered, with resolution of cardiotoxicity within 2–4 days following ingestion.

CONCLUSIONS:

We recommend that all patients with an overdose of bupropion should have an electrocardiogram performed on admission and should be monitored for the development of conduction delays and/or life-threatening arrhythmias.
Branded versus Generic Clozapine for Treatment of Schizophrenia
Authors: Makela Eugene H , Cutlip William D , Stevenson James M , Weimer Jason M , Abdallah Ehab S , Akhtar Raja S , Aboraya Ahmed S , Gunel Erdogan
Published: June 2003

OBJECTIVE:

To report clinical findings resulting from a switch from branded to generic clozapine.

METHODS:

Twenty patients diagnosed with schizophrenia were followed in this naturalistic outpatient study. The Positive and Negative Syndrome Scale (PANSS), Beck Anxiety Inventory (BAI), Abnormal Involuntary Movement Scale, and the Movement Disorder Assessment were used to assess differences in the clinical status of patients before and after switching from Clozaril to generic clozapine (Mylan Pharmaceuticals). Results were analyzed by means of the paired t-test and by calculation of the percent change in mean scores. A clinically significant change as measured by the PANSS was defined as a ± 20% change in mean scores at final evaluation. The design was open-label and non-blinded.

RESULTS:

At the final evaluation, the t-test revealed no significant differences between branded and generic clozapine for the total PA NSS, the positive symptom, negative symptom, and the general psychopathology subscales of the PANSS, and the BAI. There were no clinically significant changes for any measure.

CONCLUSIONS:

In this small group of patients with schizophrenia, no deterioration in clinical status in several domains was noted after changing from branded to generic clozapine. This finding is consistent with pharmacologic data suggesting bioequivalence of the 2 products. Results, however, must be interpreted cautiously due to the lack of optimal study controls and small sample size.