Abstract/Text: STUDY OBJECTIVE: We investigate adverse drug events associated with antidotes ethanol and fomepizole in methanol or ethylene glycol poisonings. An "adverse drug event" is harm associated with normal or incorrect drug use. We describe type, frequency, severity, seriousness, and onset time of adverse drug events and test the hypothesis that fomepizole results in fewer adverse drug events than ethanol.
METHODS: This cohort study included patients aged 13 years or older, hospitalized between 1996 and 2005 for methanol or ethylene glycol poisoning (identified by International Classification of Diseases, Ninth Revision or 10th Revision codes) and treated with at least 1 dose of ethanol or fomepizole. Two abstractors separately reviewed each chart, identifying new clinical events during antidote treatment. Three toxicologists determined, by consensus, which events were adverse drug events. The primary outcome was at least 1 adverse drug event, expressed as adverse drug event rate per person-day of antidote treatment. Association between time to first adverse drug event and antidote type was modeled by Cox regression, adjusted for confounders.
RESULTS: Two hundred twenty-three charts were reviewed and 172 analyzed. Toxicologists identified at least 1 adverse drug event in 74 of 130 (57%) ethanol-treated and 5 of 42 (12%) fomepizole-treated cases. Central nervous system symptoms accounted for most adverse drug events (48% ethanol-treated, 2% fomepizole-treated). Severe adverse drug events occurred in 26 of 130 (20%) ethanol-treated (coma, extreme agitation, cardiovascular) and 2 of 42 (5%) fomepizole-treated (coma, cardiovascular). Serious (life-threatening) adverse drug events occurred in 11 of 130 (8%) ethanol-treated (respiratory depression, hypotension) and 1 of 42 (2%) fomepizole-treated (hypotension, bradycardia) cases. Median adverse drug event onset was within 3 hours after the start of either antidote. Ethanol and fomepizole adverse drug event rates were 0.93 and 0.13 adverse drug events per treatment-day, respectively. Adjusted hazard ratio was 0.16 (95% confidence interval 0.06, 0.40).
CONCLUSION: Given observational study limitations, results suggest lower occurrence of adverse drug events with fomepizole than ethanol.