Analysis of fomepizole safety based on a 16-year post-marketing experience in France.

Introduction: Fomepizole has been recommended as first-line antidote to treat ethylene glycol and methanol poisoning. Despite more than 30 years of utilization, the safety of fomepizole when used clinically has not been well documented. Based on the long-standing clinical experience with fomepizole in France, we investigated its safety profile in patients treated for suspected toxic alcohol poisoning.Methods: We designed a 16-year post-marketing study to evaluate the indications for fomepizole prescriptions and to investigate its safety. Data were retrospectively collected using a standardized questionnaire sent each month by post to each French hospital that ordered fomepizole during the month before. The response rate to our survey was 59%.Results: Five hundred and thirty-six patients [188 females/348 males; age, 46 years [34-55] (median [25th-75th percentiles])] were treated with fomepizole [cumulative dose, 18.6 mg/kg [15.5-26.3] (1,268 mg [900-2,100])]. Ethylene glycol/methanol poisoning was confirmed in 275 patients (51%) while a nontoxic exposure was diagnosed in 147 patients (27%). Toxic alcohol poisoning was misdiagnosed in the remaining 114 patients (21%), before the assessment of an alternative poisoning or non-poisoning diagnosis. Fifty adverse reactions were attributed to fomepizole in 36 patients (7%) including general reactions (N = 22), local reactions (N = 22) and laboratory test impairments (N = 6). All were considered mild and transient. None required stopping fomepizole. The most frequent adverse effects were injection site pain/burning (N = 13), nausea/vomiting (N = 8), vessel puncture site inflammation (N = 7), drowsiness/confusion (N = 5) and serum aminotransferase elevation (N = 3). None of the fatalities (N = 37, 7%) or persistent symptoms on discharge (N = 9; 2%) was related to fomepizole.Conclusion: Our longitudinal cohort study supports the safety of fomepizole administered to treat presumed EG and methanol poisoning.

Fomepizole to treat disulfiram-ethanol reaction: a case series.

Introduction: Disulfiram-ethanol reaction (DER) due to acetaldehyde accumulation occurs after drinking ethanol during disulfiram therapy. DER may result in life-threatening toxicity requiring urgent critical care. Fomepizole, an alcohol dehydrogenase inhibitor used to treat toxic alcohol poisoning, has been suggested for treating DER by preventing the metabolism of ethanol to acetaldehyde. However, its effectiveness and safety have been poorly assessed in this setting.Cases: Ten DER patients (median age, 40 years; 7 males/3 females) were included in the study. DER features consisted of consciousness impairment (median Glasgow coma score, 13; need for mechanical ventilation, 30%) with flushing (50%), vomiting (40%), electrocardiogram abnormalities (30%) and circulatory failure requiring norepinephrine (30%). Patients were successfully treated with a single intravenous infusion of fomepizole (median dose, 7.5 mg/kg). The three patients receiving norepinephrine did not improve until fomepizole was administered. The other seven patients improved promptly following fomepizole infusion without requirement for vasopressor support. All patients fully recovered. Local pain at the injection site was the only reported adverse reaction in one patient.Conclusion: Our case series supports the effectiveness and safety of fomepizole in rapidly reversing DER-induced vasodilatation and toxicity.