BC moving to simplified IV N-acetylcysteine protocol for acetaminophen overdose

The BC Drug and Poison Information Centre (DPIC) will be transitioning to a standardized, pan-Canadian protocol for intravenous N-acetylcysteine (NAC) for the treatment of acetaminophen overdose.

The current three-bag regimen will be replaced by a single concentration given in two steps. DPIC is prepared to launch the provincewide transition to the revised protocol by 1 November 2026, though individual health authorities may launch at earlier or later dates. The goal is for all BC health authorities to complete the transition by the end of 2026.

The change is in response to safety concerns raised by the Institute for Safe Medication Practices Canada, which identified inconsistent protocols and complex dosing stages as contributors to NAC infusion errors.[1] The traditional three-bag regimen required three separate preparations and concentrations, and medication errors have been reported in up to 33% of cases.

The new regimen uses a standardized 3% (30 mg/mL) solution, and the simplified protocol involves a loading dose of 150 mg/kg over 1 hour, then reducing the infusion rate to 15 mg/kg/h as a continuous maintenance infusion for at least 20 hours. The total dose of NAC delivered over the first 21 hours is 450 mg/kg, compared to 300 mg/kg with the three-bag protocol, providing greater protection in cases of massive overdose or established hepatotoxicity. In addition, the revised protocol no longer requires ad hoc dose adjustment in massive overdoses or for patients on hemodialysis.

The new protocol also includes clearer stopping criteria, with the infusion continued until all of the following are met: 

• Acetaminophen below 66 µmol/L.
• Alanine aminotransferase and/or aspartate aminotransferase normal or declining by more than 25% from peak.
• INR below 2.0 and falling (without the use of fresh frozen plasma).
• Patient is clinically well, without evidence of encephalopathy.

Order sets, infusion references, and monographs in each health authority will be aligned with the revised protocol. Clinicians who manage acetaminophen overdose are encouraged to review the changes and the order sets at their local institutions.

DPIC is available 24 hours a day at 1 800 567-8911 for advice on suspected or confirmed acetaminophen overdose and for questions about the transition.

For more information from BC DPIC, see the NAC two dose for acetaminophen toxicity resource page: www.dpic.org/content/n-acetylcysteine-nac-2-dose-acetaminophen-toxicity-....
—Daniel Ovakim, MD, FRCPC
Medical Toxicologist, BC Drug and Poison Information Centre

References

1.       Institute for Safe Medication Practices Canada. When the antidote causes harm: Preventing errors with intravenous acetylcysteine. ISMP Canada Safety Bulletin. 2023;23. Accessed 19 September 2026. https://ismpcanada.ca/bulletin/when-the-antidote-causes-harm-preventing-....