Role of fomepizole in the management of ethylene glycol toxicity.
OBJECTIVE
To systematically review English-language articles on fomepizole administration in patients with ethylene glycol poisoning.


METHODS
MEDLINE, EMBASE, Current Contents, and PubMed. Search terms were fomepizole, 4-methylpyrazole, and ethylene glycol. The search was supplemented with a bibliographic review of all relevant articles.


METHODS
All published reports of fomepizole administration in patients with ethylene glycol poisoning were reviewed, irrespective of study design. We identified one clinical trial and subsequent pharmacokinetic study, one case series, and 13 case reports.


RESULTS
Fomepizole has been investigated in 70 patients in open, unblinded studies. Most patients received an intravenous loading dose, with subsequent variable maintenance doses every 12 hours until plasma ethylene glycol levels became undetectable. Additional hemodialysis treatment generally was administered when patients had renal insufficiency or ethylene glycol levels above 50 mg/dl. Many patients had detectable ethanol levels either because of coadministration or as a result of adjunctive treatment at a referring center. Poorer patient outcomes, such as death and renal insufficiency, were associated with later clinical presentation time after ingestion. At therapeutic fomepizole levels (> 8.6 mg/ml), the half-life of ethylene glycol was prolonged to over 19 hours. Fomepizole appeared to be well tolerated by most patients.


CONCLUSIONS
Fomepizole is an effective alcohol dehydrogenase inhibitor that decreases production of ethylene glycol metabolites. Reduced mortality and morbidity are undetermined because of the small number of patients evaluated to date. Data on comparative efficacy of fomepizole versus ethanol and data on administration of fomepizole in children are limited.
Druteika
Deon P
DP
Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Zed
Peter J
PJ
Ensom
Mary H H
MH
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors; D000931:Antidotes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000431:Ethanol / Q000008:administration & dosage; D019855:Ethylene Glycol / Q000097:blood / Q000378:metabolism / Q000506:poisoning*; D000077604:Fomepizole; D006801:Humans; D016239:MEDLINE; D011041:Poisoning / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006435:Renal Dialysis; D016896:Treatment Outcome
D000931:Antidotes; D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D019855:Ethylene Glycol