Background Fomepizole has been suggested as adjunctive therapy for severe acetaminophen poisoning though clinical efficacy is unknown. We sought to determine trends in the use of fomepizole for acetaminophen poisoning.

Methods This is a cross-sectional analysis of hospitalized patients with acetaminophen poisoning from January 2013 through December 2024, using Epic Cosmos, a research database of 298 million patients nationally. We identified encounters involving acetaminophen poisoning by International Classification of Diseases, version 10 (ICD-10-CM) code. Data extracted included administration of N-acetylcysteine (NAC) and fomepizole, demographic data, and outcomes of death and liver transplantation. Data were analyzed using descriptive statistics to identify trends and multivariable logistic regression to determine associations with death or liver transplant.

Results There were 114,111 hospital encounters involving acetaminophen poisoning with 64,957 (56.92%) receiving NAC, and 1,552 (1.36%) receiving fomepizole. In 2013, 0.44% of NAC-treated acetaminophen poisoning cases also received fomepizole. This rose to 6.27% in 2024. From 2013 to 2019, the proportion of NAC-treated acetaminophen cases receiving fomepizole was stable, but from 2019-2024, there was a 1029.64% increase in fomepizole use. Regression modeling indicated increased odds for death (OR=5.88, aOR=5.32 [95% CI: 4.52, 6.27]) and liver transplantation (OR=4.99, aOR=4.91 [95% CI: 2.10, 11.48]) among those who received fomepizole in addition to NAC, indicating increased fomepizole use in patients with severe toxicity.

Conclusion Fomepizole use in acetaminophen poisoning has risen dramatically since 2019, particularly among patients at highest risk for death and liver transplantation. It is of critical importance to determine the efficacy of fomepizole for acetaminophen poisoning.

The authors have declared no competing interest.

This study did not receive any funding

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Board of the University of Illinois Chicago waived ethical approval for this work.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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The data that support the findings of this study are available from Epic Cosmos. Restrictions apply to the availability of these data, which were used under license for this study. Data are available from https://cosmos.epic.com with the permission of Epic Cosmos.

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