Note. The image was created in original work from author’s T.M. and L.Q. adapted from research and information sourced from Mazaleuskaya LL, Sangkuhl K, Thorn CF, FitzGerald GA, Altman RB, Klein TE. PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015;25(8):416-426. doi:10.1097/FPC.0000000000000150. This image is a direct illustration from the author’s personal collection: Miller, T.J., Qiu, L. (2025). Metabolic Processing Flowchart of Acetaminophen. Author’s personal collection.
Discussion:
While general recommendations advise not exceeding 4,000 mg/day in adults, applying an individualized patient-based approach is essential in avoiding “one-regimen-fits-all” dosing that may still be toxic to certain adult patients (3, 4). Here, this case clearly demonstrates how at-risk subpopulations can develop clinically significant complications from normal acetaminophen dosing. Old age and weight loss are frequent co-passengers in overall diminished metabolic processing capacity, and given this patient’s advanced age and thin habitus, a weight-based dosing system used routinely for pediatric patients should have been considered (4, 6). With this approach, her initial acetaminophen dose of roughly 30 mg/kg/dose (total 3,087 mg daily) would have been noted to be 66% more than the standard weight-based dosing for pediatric patients (15 mg/kg/dose at q6hr; total 2,058 mg daily). Comparing the discrepancy between these two methods can help appropriately raise concerns for the prescribing provider and allow them to err on the more conservative side given a patient’s full clinical picture. Standardized drug regimens provide a safe, validated, and efficient way to deliver care, but providers should remain wary of the harm behind their universal application in patients who are not standard.
References:
1. Salgia AD, Kosnik SD. When acetaminophen use becomes toxic. Treating acute accidental and intentional overdose. Postgrad Med. 1999;105(4):81-90. doi:10.3810/pgm.1999.04.673
2. Boudrias-Dalle E, Chen A. Acetaminophen Dose Considerations in Frail and Malnourished Elderly Patients: A Case Report of Hepatotoxicity with Therapeutic Doses. Can J Hosp Pharm. 2023;76(4):337-339. Published 2023 Sep 1. doi:10.4212/cjhp.3415
3. Gerriets V, Anderson J, Patel P, Nappe TM. Acetaminophen. In: StatPearls. Treasure Island (FL): StatPearls Publishing; January 11, 2024.
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5. European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; Clinical practice guidelines panel, Wendon, J, et al. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol. 2017;66(5):1047-1081. doi:10.1016/j.jhep.2016.12.003
6. Shah NJ, Royer A, John S. Acute Liver Failure. In: StatPearls. Treasure Island (FL): StatPearls Publishing; April 7, 2023.
7. Miller, T.J., Qiu, L. (2025). Metabolic Processing Flowchart of Acetaminophen. Author’s personal collection.
8. Mazaleuskaya LL, Sangkuhl K, Thorn CF, FitzGerald GA, Altman RB, Klein TE. PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics . 2015;25(8):416-426. doi:10.1097/FPC.0000000000000150