Purpose Acetaminophen (APAP) is a ubiquitous antipyretic and analgesic used in children in the United States (US), including those with cancer. The effects of US Food & Drug Administration (FDA) guidance on APAP prescribing have been described for healthy adults and children; however, APAP use patterns in children with cancer are unknown. Considering their increased risk of liver injury, APAP’s potential for causing hepatoxicity, and FDA guidance changes, this study examined the recent evolution of APAP use in children with cancer.

Methods This retrospective, multi-center analysis extracted APAP prescribing data from the Pediatric Health Information System® (PHIS). Eligible children were aged 0-26 years, had a cancer diagnosis per International Classification of Diseases (ICD) codes, and were prescribed a chemotherapeutic. APAP and APAP-opioid combination prescribing were assessed at hospital, regional, and national levels. Changes in APAP and APAP-opioid combination use rates were assessed using the non-parametric Mann-Kendall test.

Findings PHIS records for the complete years of 2004-2021 yielded 388,364 inpatient encounters for 50,779 unique patients. Of these, 87.3% of patients received APAP. Although APAP-opioid combination use was infrequent overall, children receiving APAP were more likely to receive an APAP-opioid combination medication (N=25,880, 13.4%, p < 0.001) compared to those who did not receive APAP. Among specialty children’s hospitals, national APAP use was stable over the study period. Regionally, APAP use increased among hospitals in the Northeast. APAP-opioid combination use decreased nationally with regional variation. In contrast to the steady decline in other regions, Southern APAP-opioid combination use was consistently elevated before declining in 2014.

Implications This article describes acetaminophen and acetaminophen-opioid prescribing trends among children with cancer in the United States. These trends are key to help clinicians assess changes in pain management strategies over time, contextualize analgesic exposure and efficacy, and provide a foundation for future studies in drug safety. Extensive acetaminophen use can affect liver health, and further work is needed to evaluate acetaminophen exposure in children with cancer.

Data Statement Deidentified data were obtained and evaluated under an IRB-approved protocol. Due to privacy requirements, the data are not available to be shared.

Dr. Maese is affiliated with Jazz Pharmaceuticals as a member of the advisory board, consultant, and speakers bureau. Dr. Maese is also affiliated with Servier Pharmaceuticals as a member of the advisory board and consultant.

This work was supported by the National Institutes of Health NIH1K22CA258671-01A1 (JEC) and NIH NCATS CCTS-PCHF-002580 (JEC).

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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 Boards of Intermountain Healthcare and the University of Utah gave ethical approval for this work.

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↵‡ denotes co-first authorship.

Conflict of Interest Disclosures: Dr. Maese is affiliated with Jazz Pharmaceuticals as a member of the advisory board, consultant, and speakers bureau. Dr. Maese is also affiliated with Servier Pharmaceuticals as a member of the advisory board and consultant.

Funding/Support: This work was supported by the National Institutes of Health NIH1K22CA258671-01A1 (JEC) and NIH NCATS CCTS-PCHF-002580 (JEC).

Role of Funder/Sponsor (if any): Not Applicable.

Deidentified data were obtained and evaluated under an IRB-approved protocol. Due to privacy requirements, the data are not available to be shared.