Fomepizole as an adjunct in acetylcysteine treated acetaminophen overdose patients: a case series. (3rd April 2022)

• Record Type: Journal Article
• Authors: Link, Stephanie L.; Rampon, Garrett; Osmon, Stephen; Scalzo, Anthony J.; Rumack, Barry H.
• Is Part Of: Clinical toxicology. Volume 60:Number 4(2022)
• Page Start: 472
• Page End: 477
• Publication Date: 2022-04-03
• Subjects: Acetaminophen -- APAP -- acetylcysteine -- fomepizole -- hepatotoxicity; Toxicology -- Periodicals; Toxicological emergencies -- Periodicals; 615.9
• DOI: 10.1080/15563650.2021.1996591
• Languages: English
• ISSNs: 1556-3650

Abstract

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.