Clinical impact of fomepizole as an adjunct therapy in high-risk acetaminophen overdose

Abstract

Introduction: The objectives of this study were to characterize and compare clinical outcomes in patients with high-risk acetaminophen overdose who received fomepizole as an adjunct to N-acetylcysteine treatment to those who received N-acetylcysteine only.

Material and methods: This was a retrospective cohort study of patients reported to four United States poison control centers between January 2018 and December 2022. Patients with high-risk acetaminophen ingestion-defined as a serum concentration ≥ 300 μg/mL at 4 h or more post-ingestion, or a multiplication product (acetaminophen concentration in mcg/mL multiplied by either aspartate aminotransferase in units per liter or alanine aminotransferase in units per liter) ≥10,000-upon admission who received N-acetylcysteine were included. Exclusion criteria included documented history of pre-existing liver disease, insufficient case details, or co-ingestion of either a toxic alcohol or another hepatotoxic substance. Clinical characteristics and outcomes were compared using logistic regressions between patients who received fomepizole as an adjunct to N-acetylcysteine treatment to those who received N-acetylcysteine only. A subgroup analysis assessed the impact of fomepizole timing (≤24 h versus >24 h) after N-acetylcysteine initiation.

Results: Among the 391 patients included, there were no significant differences in National Poison Data System outcome severity, intensive care unit stay, or N-acetylcysteine duration between patients who received fomepizole and those who did not. In the subgroup analysis of fomepizole recipients, outcomes were also similar regardless of whether fomepizole was administered within or after 24 h of N-acetylcysteine initiation.

Discussion: Fomepizole as an adjunct to N-acetylcysteine in patients with high-risk acetaminophen overdose did not improve clinical outcomes. Although no adverse effects to fomepizole were reported, routine use in this setting remains unsupported by this study.

Keywords: Acetaminophen; Fomepizole; High-risk; Liver failure; Overdose; Toxicology.