Should N‐Acetylcysteine be Administered Orally or Intravenously for the Treatment of Paracetamol Overdose?

Paracetamol is the most commonly used drug in deliberate poisoning. N‐acetylcysteine is the standard antidote for significant acute paracetamol overdose, but the route of administration varies between countries. This review aimed to find and appraise those comparative studies which would help answer the following question: in patients who have taken an overdose of paracetamol requiring antidote, is there any difference between intravenous and oral N‐acetylcysteine in mortality, hepatotoxicity, adverse drug reactions or cost? Methods A literature search was conducted using Medline and other databases. Relevant papers were identified and appraised. Results One animal study and seven comparative clinical studies were identified and appraised. The quality of the evidence was generally poor, and there was no clear difference in outcomes between the two routes of administration. Conclusions Without evidence of advantage for one route over the other, routine practice should not be changed. However, after 30 years experience, both routes appear to be effective and safe, and in countries where intravenous administration is the standard, it would be reasonable to consider the oral route as an alternative when intravenous access is problematic. There is a need for prospective, randomised trials to determine the relative effectiveness, safety and cost of intravenous and oral formulations of N‐acetylcysteine.