Fomepizole as an adjunct in acetylcysteine treated acetaminophen overdose patients: a case series.

Abstract

INTRODUCTION:

Acetaminophen (N-acetyl-para-aminophenol or APAP) is the leading cause of acute liver failure worldwide. Standard therapy for APAP overdose is with IV N-acetylcysteine (NAC). However, overdose patients treated with NAC can still incur hepatotoxicity in some circumstances. Fomepizole has proven safety in methanol and ethylene glycol poisoning and is a potent CYP2E1 and c-Jun-N-terminal Kinase (JNK) inhibitor that is effective even in the metabolic phase.

METHODS:

We present a prospective case series of 14 consecutive, high-risk patients who had elevated APAP levels after overdose who were treated with fomepizole as an adjunct to standard IV-NAC. The attending toxicologist utilized clinical judgement to determine the use of fomepizole, especially if APAP levels persisted due to altered half-life or risk factors for toxicity.

RESULTS:

There were no unfavorable outcomes in any patient, which were better than expected.

CONCLUSIONS:

This case series has demonstrated the safety of fomepizole in high-risk APAP overdose. The efficacy of fomepizole needs to be further elucidated through controlled clinical trials on a larger scale. In massive APAP overdoses, fomepizole should be considered as an adjunct due to the known failure rate of NAC and the safety profile of fomepizole.

• Authors: Stephanie L Link, Garrett Rampon, Stephen Osmon, Anthony J Scalzo, Barry H Rumack
• Journal: Clinical toxicology (Philadelphia, Pa.) (Clin Toxicol (Phila)) Vol. 60 Issue 4 Pg. 472-477 (Apr 2022) ISSN: 1556-9519 [Electronic] England
• PMID: 34709101 (Publication Type: Journal Article)

Chemical References

• Antidotes
• Acetaminophen
• Fomepizole
• Acetylcysteine

Topics

• Acetaminophen
• Acetylcysteine (therapeutic use)
• Antidotes
• Chemical and Drug Induced Liver Injury (drug therapy, etiology)
• Drug Overdose (drug therapy)
• Fomepizole
• Humans