Supratherapeutic Dosing of Acetaminophen Among Hospitalized Patients

Li Zhou, MD, PhD; Saverio M. Maviglia, MD, MS; Lisa M. Mahoney, RPh; Frank Chang, MSE; E. John Orav, PhD; Joseph Plasek, MS; Laura J. Boulware; Hong Lou; David W. Bates, MD, MSc; Roberto A. Rocha, MD, PhD

Arch Intern Med. 2012;172(22):1721-1728. doi:10.1001/2013.jamainternmed.438.

ABSTRACT.

Background  We investigated acetaminophen use and identify factors contributing to supratherapeutic dosing of acetaminophen in hospitalized patients.

Methods  We retrospectively reviewed the electronic health records of adult patients who were admitted to 2 academic tertiary care hospitals (hospital A amd hospital B) from June 1, 2010, to August 31, 2010, and who received acetaminophen during their hospitalization. Patients' acetaminophen administration records (including drug name, dose, administration time, hospital units, etc), demographic data, diagnoses, and results from liver function tests were obtained. The main outcome measures included acetaminophen exposure rate and supratherapeutic dosing rate among hospitalized patients, hazard ratios (HRs) and 95% confidence intervals (CIs) for risk factors for supratherapeutic dosing, and changes in liver function test before and after supratherapeutic dosing.

Results  A total of 14 411 patients (60.7%) were exposed to acetaminophen, of whom 955 (6.6%) exceeded the 4 g per day maximum recommended dose. In addition, 22.3% of patients who were 65 years or older and 17.6% of patients with chronic liver diseases exceeded the recommended limit of 3 g per day. Patients receiving excessive doses of acetaminophen tended to have significant alkaline phosphatase elevations, although causal relationship cannot be concluded. A significantly higher risk of supratherapeutic dosing was observed in hospital A (HR, 1.6 [95% CI, 1.4-1.8]), white patients (HR, 1.5 [95% CI, 1.3-1.7]), patients diagnosed as having osteoarthritis (HR, 1.4 [95% CI, 1.3-1.6]), and those who received scheduled administrations (HR, 16.6 [95% CI, 13.5-20.6]), multiple product formulations (HR, 2.4 [95% CI 2.0-2.9]), or the 500-mg strength formulation (HR, 1.9 [95% CI, 1.5-2.3]). A lower risk was found for pro re nata (as needed) administrations (HR, 0.7 [95% CI, 0.6-0.9]) and in nonsurgical and non–intensive care units (HR, 0.6 [95% CI, 0.5-0.7]).

Conclusions  Supratherapeutic dosing of acetaminophen was significantly associated with multiple factors. Interventions to reduce the incidence of some risk factors may prevent supratherapeutic acetaminophen dosing in hospitalized patients.