- Medicines and Healthcare products Regulatory Agency
- 19 January 2017
- Therapeutic area:
- Anaesthesia and intensive care
The authorised dose regimen for N-acetylcysteine (NAC) in paracetamol overdose is 3 consecutive bags given intravenously over 21 hours. Prescribing information is being updated to advise that continued treatment with NAC may be necessary depending on clinical evaluation of the individual patient.
Advice for healthcare professionals:
- the authorised posology for intravenous N-acetylcysteine (NAC) in the treatment of paracetamol overdose is 3 consecutive intravenous infusions
- first infusion: initial loading dose of 150 mg/kg bodyweight over 1 hour
- second infusion: 50 mg/kg over the next 4 hours
- third infusion: 100 mg/kg over the next 16 hours
- the patient should receive a total dose of 300 mg/kg bodyweight over a 21-hour period. A ceiling weight of 110 kg should be used when calculating the dose for obese patients
- continued treatment with NAC (given at the dose and rate as used in the third infusion) may be necessary depending on the clinical evaluation of the individual patient
Intravenous NAC is the antidote to treat paracetamol overdose and is virtually 100% effective in preventing liver damage when given within 8 hours of the overdose. After this time efficacy falls substantially, affording only a very limited window of time in which to successfully prevent serious hepatotoxicity.
Simplified guidance on the treatment of paracetamol overdose with NAC was implemented in September 2012, after an evidence-based review by the Commission on Human Medicines (CHM).
Since 2012, data for an off-label shortened 2-bag regimen for NAC to treat paracetamol overdose have been published from the Scottish and Newcastle Antiemetic Pre-treatment for paracetamol poisoning (SNAP) study.1 CHM have reviewed these findings and, as part of their review, also looked at the safety profile of NAC since the 2012 guidance was implemented.
CHM concluded that there was insufficient evidence of efficacy to add information about the off-label shortened 2-bag dose regimen used in the SNAP study to the product information for NAC.
The pattern of potential adverse drug reactions associated with NAC is well established, and no new safety issues have been identified since the 2012 guidance. The authorised NAC product information reflects the safety profile. CHM concluded that the benefits of the authorised 3-bag dose regimen continue to outweigh the risks. As with all medicines, suspected adverse reactions should continue to be reported to us on a Yellow Card.
Potential need to continue treatment: prescribing update
As a result of the review, in line with current clinical guidance, prescribing information for NAC is being updated to advise that continued treatment with NAC beyond 21 hours may be necessary depending on the clinical evaluation of the individual patient.
Article citation: Drug Safety Update volume 10 issue 6, January 2017: 4.
Bateman DN, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet 2014; 383: 697–704. ↩
Published: 19 January 2017
Therapeutic area: Anaesthesia and intensive care