Sufficient evidence of efficacy is available to support extending the time of the initial infusion from 15 minutes to 60 minutes in order to reduce the incidence of adverse reactions. The majority of common dose-related adverse reactions occur within the first hour of the initial infusion of acetylcysteine. The CHM recommended a number of measures to reduce the incidence of administration errors, most notably the introduction of weight-based dosage tables for adults and children to remove the need to calculate the dose. A major contributory factor for these errors was the complex dosing regimen for intravenous acetylcysteine. In the past there were also a substantial number of reports of administration errors with intravenous acetylcysteine, some of which had the potential to result in significant harm. By removing the need to assess risk factors for hepatotoxicity, the approved indication for acetylcysteine is greatly simplified to a single line on the paracetamol overdose treatment nomogram (figure 1).

The CHM review found that the evidence base to support the use of risk factors was poor and inconsistent, and that many of the risk factors for hepatotoxicity were imprecise and difficult to determine with sufficient certainty in clinical practice. This resulted in two lines on the treatment nomogram – 1 for patients with risk factors and 1 for those without. Previously, healthcare professionals treating paracetamol overdose were advised to assess for risk factors of hepatotoxicity such as chronic alcohol consumption, co-medications and poor nutritional intake.

New simplified guidance on the treatment of acute paracetamol overdose with acetylcysteine is now in place, following an evidence-based review by the Commission on Human Medicines (CHM). After this time efficacy falls substantially, affording only a very limited window of time in which to successfully prevent serious hepatotoxicity. Intravenous acetylcysteine is the antidote to treat paracetamol overdose and is virtually 100% effective in preventing liver damage when given within 8 hours of the overdose. Paracetamol overdose can result in liver damage which may be fatal.

Paracetamol antidote dose