Hepatotoxicity may occur after a single ingestion of more than 150 mg/kg paracetamol taken in less than 1h, though rarely ingestions as low as 75 mg/kg have produced hepatotoxicity. Hepatotoxicity is more likely if there is hepatic enzyme induction due to chronic alcohol use or drug therapy (carbamazepine, phenobarbitone, phenytoin, rifampicin), or if there is depletion of hepatic glutathione as in anorexia or AIDS. Acetylcysteine (AC) replenishes hepatic glutathione and is the preferred antidote.

• For patients weighing more than 110kg who are obese (body mass index >30), use a body weight of 110kg rather than actual body weight when calculating dose of paracetamol ingested (in mg/kg).
• The plasma paracetamol level is a poor guide to the risk of hepatotoxicity in patients with staggered poisoning (overdose taken over a period of longer than 1h or multiple ingestions within a 24-h period). If the total amount taken is >150 mg/kg in a 24-h period, or the patient is at increased risk of liver damage, acetylcysteine should be given.