Trends in Fomepizole Use for Acetaminophen Poisoning in the United States; 2013-2024

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.

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.

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.

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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study did not receive any funding Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes 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. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes 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). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability 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.