Adverse Drug Events Associated With the Antidotes for Methanol and Ethylene Glycol Poisoning: A Comparison of Ethanol and Fomepizole

Presented at the North American Congress of Clinical Toxicology, October 2007, New Orleans, LA.

Received 22 September 2007; received in revised form 31 January 2008 and 28 April 2008; accepted 5 May 2008. published online 21 July 2008.

Refers to article:

Ethanol: Tastes Great! Fomepizole: Less Filling! , 05 November 2008
Marco L.A. Sivilotti
Annals of Emergency Medicine
April 2009 (Vol. 53, Issue 4, Pages 451-453)
Full Text | Full-Text PDF (251 KB)

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.

a British Columbia Drug and Poison Information Centre, Vancouver, British Columbia, Canada

b University of British Columbia, School of Population and Public Health, Vancouver, British Columbia, Canada

c Centre for Health Evaluation and Outcome Sciences at St. Paul's Hospital, Vancouver, British Columbia, Canada

d Centre for Clinical Epidemiology and Evaluation at Vancouver General Hospital, Vancouver, British Columbia, Canada

e Vancouver General Hospital, Department of Emergency Medicine, Vancouver, British Columbia, Canada

f St. Paul's Hospital, Department of Emergency Medicine, Vancouver, British Columbia, Canada

g Department of Internal Medicine, Vancouver, British Columbia, Canada

h Royal Columbian Hospital, Department of Emergency Medicine, New Westminster, British Columbia, Canada

Address for correspondence: Katherine J. Lepik, BSc(Pharm), MSc, British Columbia Drug and Poison Information Centre, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6; 604-682-5050, fax 604-806-8262

Supervising editor: E. Martin Caravati, MD, MPH

Author contributions: KJL, ARL, BGS, RAP, and DED conceived and designed the study. KJL and JLB performed data collection. RAP, CRD, GDE, and JRK acted as expert reviewers. BGS was the senior statistician. KJL analyzed the data. KJL drafted the article, and all authors contributed substantially to its revision. KJL takes responsibility for the paper as a whole.

Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article, that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. KJL was supported by a training fellowship from the Michael Smith Foundation for Health Research (MSFHR). ARL is supported by MSFHR Senior Scholar and Canadian Institutes of Health Research New Investigator awards. BGS was supported by the Canada Research Chair Program.

Publication dates: Available online July 18, 2008.

Earn CME Credit: Continuing Medical Education is available for this article at: www.ACEP-EMedHome.com.

Reprints not available from the authors.

PII: S0196-0644(08)00796-8

doi:10.1016/j.annemergmed.2008.05.008

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