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.

Keywords:

• Acetaminophen
• APAP
• acetylcysteine
• fomepizole
• hepatotoxicity

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Correction

Correction Statement

This article was originally published with errors, which have now been corrected in the online version. Please see Correction (http://dx.doi.org/10.1080/15563650.2021.2007599).

Disclosure statement

Stephanie L. Link, Garrett Rampon, Stephen Osmon, Scalzo: No disclosures. Barry H. Rumack: Provided consultation regarding acetaminophen adducts for Johnson and Johnson in 2019.

Additional information

Funding

This work was not supported by any funding.