Fomepizole as an adjunctive therapy for acetaminophen poisoning: cases reported to the toxicology investigators consortium (ToxIC) database 2015–2020

Abstract

Introduction

Fomepizole inhibits formation of toxic acetaminophen (APAP) metabolites and may prevent or reverse mitochondrial toxicity. Given these mechanisms, it may be beneficial in patients with severe APAP toxicity. Current patterns of use for this indication are not well-studied.

Methods

This is a secondary analysis of patients enrolled in the Toxicology Investigators Consortium (ToxIC) database from January 2015 to July 2020. We queried cases in which APAP was listed as an ingested agent and fomepizole was also administered. We excluded cases in which APAP was not the primary agent, N-acetylcysteine (NAC) was not administered, or fomepizole was explicitly administered for another indication. Additionally, we sent a survey to each ToxIC site that administered fomepizole for APAP toxicity to better understand when, why, and how they were using it for this indication.

Results

Twenty-five cases of fomepizole administration following an APAP ingestion met our inclusion criteria. There were one to four cases per year between 2015 and 2019 and eight cases in 2020. Seventeen of 25 (68%) cases were for a known acute ingestion. Eighteen of 25 (72%) patients developed hepatotoxicity (AST or ALT > 1000 IU/L) and 10 of 25 (40%) developed coagulopathy (PT > 15s). This was an ill patient population, with 18 of 25 (72%) developing metabolic acidosis (pH <7.20), 12 of 25 (48%) were intubated, 9 of 25 (36%) receiving vasopressors, and 6 of 25 (24%) receiving continuous renal replacement therapy. Overall, mortality was 24%.

Conclusion

The use of fomepizole is increasing in frequency in a small subset of critically ill and acutely APAP-poisoned patients.

Keywords:

• Acetaminophen
• paracetamol
• fomepizole
• 4-methylpyrazole
• hepatotoxicity

Acknowledgements

Data attributable to the Toxicology Investigator’s Consortium (ToxIC).

Previous presentations of data

Filip AB, Berg SE, Mullins ME, Schwarz ES, On Behalf of the ToxIC Investigators Consortium (ToxIC): “Fomepizole As An Adjunctive Therapy For Acetaminophen Poisoning: Cases Reported To The Toxicology Investigators Consortium (ToxIC) Database 2015–2020.” ACMT Annual Scientific Meeting April 14–16, 2021.

Disclosure statement

No potential conflict of interest was reported by the author(s).