The Role of Fomepizole in Acetaminophen-related Poisoning: A Narrative Review

N-acetylcysteine as the gold standard antidote may not be sufficient in managing cases of acetaminophen-related poisoning with delayed presentations or with massive ingestions. Existing human reports up until July 2021 have suggested that fomepizole may play a potential role in acetaminophen overdoses through inhibition of CYP2E1-mediated NAPQI production and JNK-mediated oxidative damage. This narrative review aims to build upon the repertoire of literature and case studies summarized by existing systematic and scoping reviews with the latest evidence regarding the use of fomepizole in acetaminophen-poisoning to better understand the hepatoprotective role and safety profile of this medication as well as its practical place in therapy. A systematic search was completed through November 2024 in MEDLINE and EMBASE. Studies involving human patients with acetaminophen toxicity who received fomepizole treatment were included. Each patient case was thoroughly summarized in tables from which clinical trends including the risk of hepatotoxicity, quantity of ingestion, time of presentation since ingestion, therapeutic and dosing regimens, and clinical outcomes were identified. A total of 30 studies and 45 patients across 18 case reports and six case series were included in this review. When used in adjunct with N-acetylcysteine, fomepizole seemed to result in favourable laboratory and clinical outcomes in most patients that were at high risk of hepatotoxicity with late presentations or massive acetaminophen ingestions. Available data suggests fomepizole may complement N-acetylcysteine in severe acetaminophen toxicity. Though lacking detailed clinical outcome analyses, case studies suggest fomepizole may improve hepatotoxicity, survival, and transplant-free days.