TOXICOLOGY/EDITORIAL Ethanol: Tastes Great! Fomepizole: Less Filling! Marco L. A. Sivilotti, MD, MSc From the Department of Emergency Medicine and Department of Pharmacology and Toxicology, Queen’s University, Kingston, Ontario, Canada, and the Ontario Poison Centre, Hospital for Sick Children, Toronto, Ontario, Canada. 0196-0644/$-see front matter Copyright © 2008 by the American College of Emergency Physicians. doi:10.1016/j.annemergmed.2008.07.038 SEE RELATED ARTICLE, P. 439. [Ann Emerg Med. 2009;53:451-453.] One of the important debates in medical toxicology during the last decade has been the choice of antidote for methanol and ethylene glycol poisoning. This debate has occurred in innumerable pharmaceutical and therapeutics committees, regional toxicology treatment centers, poison information centers, ICUs and emergency departments across the United States and Canada. In the absence of systematically collected and rigorously analyzed evidence, such debates were informed by anecdote, experience, and opinion. Many physicians were reluctant to replace a familiar and mechanistically elegant antidote such as ethanol with a pricey new drug. As a result, the debate at times resembled vocal opinion leaders arguing over beverage of choice, reminiscent of a Miller Lite beer advertisement. When immediately available and administered at the correct dose (2 important caveats), ethanol is as effective as fomepizole at inhibiting further bioactivation of the parent alcohol to the toxic acid metabolites. 1,2 Instead of contesting effectiveness, proponents of fomepizole cite a litany of practical advantages (Figure 1). Although these advantages may seem soft when contemplating the retirement of our predecessors’ favorite cordial, they are nonetheless substantial and important. Detractors of fomepizole have focused primarily on the difference in acquisition cost, limited experience, and perhaps inertia to change. Yet, as anyone who has used ethanol therapeutically can attest, it is a very difficult antidote to order, locate, administer, and titrate, with frequent delays, dosing errors, readjustment, and retesting. 3,4 No longer available in the United States as either a 5% (Hospira, oral communication, June 2008) or 10% 5 volume/volume solution of pharmaceutical grade, it usually requires extemporaneous compounding by a pharmacist from dehydrated ethanol before intravenous administration. 5 If costs were equal, few physicians would recommend ethanol over fomepizole. A recent multidisciplinary expert panel updating prior recommendations for antidote stocking in US hospitals agreed that fomepizole was the preferred antidote. 6 As experience with and access to fomepizole increase, the shift in practice during the last decade is clear (Figure 2). The careful work by Lepik et al in this issue of the Annals 7 confirms the important safety advantage of fomepizole and should help persuade those skeptics awaiting a stronger evidence base beyond anecdote and opinion. Indeed, the authors are to be congratulated on a careful and methodical analysis of adverse drug events, a burgeoning field in which rigorous analyses are still uncommon. The article is also remarkable for being one of the few head-to-head comparative studies between antidotes in humans. The investigators performed a systematic health records review of patients discharged during a 10-year span after antidotal therapy for methanol or ethylene glycol poisoning in 10 hospitals across British Columbia. Most cases were adult intentional ingestions with substantial parent drug concentrations and acidemia at presentation. Outcomes were similar between groups, as estimated by the interruption of worsening acidemia and the final Poisoning Severity Score, reflecting the comparable effectiveness of the antidotes once begun. However, a large and important difference was observed in adverse drug events, with a number needed to harm of only 2 for ethanol. Indeed, the number needed to harm severely (Glasgow Coma Scale score of Ease of administration y Fixed loading dose independent of baseline ethanol concentration y Intermittent bolus dosing every 12 hours (every 4 hours during hemodialysis) y No need for monitoring serum antidote concentrations or continuous infusion Wide therapeutic margin Absence of central nervous system depression and inebriation Absence of metabolic and biochemical adverse effects Reduced intensity of nursing care Simplification of interfacility transfer Ability to forgo hemodialysis in selected patients Safety of patient and of medical personnel Figure 1. Advantages of fomepizole over ethanol as antidote for suspected methanol and ethylene glycol poisoning. Volume , .  : April  Annals of Emergency Medicine 451