167: Acetaminophen Prescribing & Pharmacokinetic Analysis in Children, Adolescents & Young Adults With Cancer

Statement of Purpose, Innovation or Hypothesis: Although acetaminophen (Tylenol®) is the most used pain medication for children, adolescents, and young adults (CAYA) globally, overuse is unequivocally linked to liver injury. Acetaminophen-induced liver injury (AILI) is common during periods of high & chronic dosing, poor nutritional status, and polypharmacy (e.g., chemotherapy). As CAYA with cancer are highly susceptible to these AILI risk factors, we hypothesized that both acetaminophen dosing and plasma concentrations would exceed recommended guidelines in ~20% of patients. Therefore, the objective of this study is two-fold: (1) to describe inpatient acetaminophen use in CAYA with cancer and (2) to evaluate how frequently blood concentrations of acetaminophen and metabolites meet or exceed AILI thresholds. These aims support the long-term goals of this project: to develop a cancer-optimized population pharmacokinetic model; to identify covariates associated with AILI risk; and to monitor acetaminophen protein adduct formation in CAYA with cancer.

Description of Methods & Materials: Acetaminophen prescribing was retrospectively examined using electronic health records from Intermountain Health (IH). IH is a non-profit healthcare system with 385 clinics and 33 hospitals, including a tertiary care specialty children’s hospital, in the Intermountain West (primarily Utah, Idaho, Nevada) serving over 2.5 million patients. Data was collected from 1996-2023 and included demographic, laboratory, microbiologic, and prescription data. Patients were included if they were 0-26 years of age and diagnosed with cancer. Descriptive and comparative statistics were performed as appropriate using Pearson’s Chi-squared test and Wilcoxon rank sum test. To assess acetaminophen blood concentrations, we used plasma specimens collected from our existing biorepository representing >550 individual CAYA diagnosed with cancer and >18K acetaminophen specimens. Samples were selected when plasma volumes could be assayed in duplicate (≥100μL) and patients received oral acetaminophen within 15h of blood collection. Acetaminophen and metabolite (glucuronide, sulfate, cysteine, N-acetyl cysteine) concentrations were quantified via a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay.

Data & Results: The retrospective study found 5,060 patients diagnosed with cancer between 1996-2023. 61.6% of patient encounters had acetaminophen administered. Acetaminophen prescribing over time significantly increased (p < 0.001). Acetaminophen was used in 57% of visits where chemotherapy was also administered; further, dose did not differ between chemotherapy and non-chemotherapy visits. For 13.1% (n=225) of infants ( >28 days to 1 year) and 21.6% (n=914) of children (2-11 years), acetaminophen dosing exceeded weight-based guidelines (12-15 mg/kg).  Among an initial batch of 200 plasma specimens, 10% of acetaminophen and metabolite concentrations fell below the lower limit of quantification (0.01 μg/mL) and ~1% exceeded the recommended 5-20 μg/mL range.

Interpretation, Conclusion or Significance: Children with cancer are vulnerable to liver injury arising from drug exposure and toxicity. However, neither the role of acetaminophen nor associated risk factors in liver injury have been studied in this group. Our study found supratherapeutic dosing is common among infants and children, placing them at increased risk for AILI. This finding was supported by preliminary pharmacokinetic data linking overdosing to those with acetaminophen & metabolite concentrations exceeding the therapeutic range.

Disclosures:

Citations/References:

Additional Information/Authors: Not Applicable.