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.
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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:
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4. Athersuch TJ, Antoine DJ, Boobis AR, et al. Paracetamol metabolism,
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doi:10.1039/c7tx00340d
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