Evaluation of a simplified N-acetylcysteine dosing regimen for the treatment of acetaminophen toxicity

Abstract

Background: Acetaminophen overdose is the most common pharmaceutical poisoning in the US. The labeled dosing regimen for Acetadote, the only intravenous N-acetylcysteine (IV-NAC) product approved by the Food and Drug Administration (FDA) for treatment of acetaminophen toxicity, is a complex 3-step process that produces frequent medication errors. We have been using an off-label, uncomplicated dosing regimen consisting of a standard preparation of IV-NAC 30 g in 1 L of 5% dextrose in water, with a 150-mg/kg loading dose administered over 1 hour followed by an infusion of 14 mg/kg/h for 20 hours.

Objective: To evaluate the frequency of medication errors, resolution of hepatotoxicity, and tolerability of the protocol used in our institution for treatment of acetaminophen toxicity.

Methods: This single-center, retrospective chart review evaluated patients receiving IV-NAC for acetaminophen toxicity from August 2006 to August 2008. Charts were reviewed for prescribing practices, dosing errors, and clinical outcomes.

Results: Among 70 patients who met inclusion criteria, 35 medication errors occurred, including 22 administration errors and 13 protocol initiation errors. The frequency of administration errors was 13.5 errors per 100 administration interventions. Loading dose errors were most common with 11 rate-related and 8 dose-related errors. Interruptions longer than 60 minutes occurred in only 3 patients. No adverse outcomes were associated with medication errors. The mean (SD) duration of therapy was 25.6 hours (n = 60 pts. [17.8], range 1-76.5), and mean length of stay was 2.99 days ([3.82], range 0.1-25.7). All patients with hepatotoxicity (aspartate aminotransferase >1000 units/L) due to acute acetaminophen toxicity had resolution of the toxicity and were successfully discharged.

Conclusions: This single intravenous bag protocol is effective and well tolerated, and there is infrequent interruption of therapy. The overall rate of administration errors is similar to that in reports on the FDA regimen; thus, our protocol may be an acceptable alternative.