As little as 10–15 g (20–30 tablets) or 150 mg/kg of paracetamol taken within 24 hours may cause severe hepatocellular necrosis and, much less frequently, renal tubular necrosis.
Nausea and vomiting, the only early features of poisoning, usually settle within 24 hours. Persistence beyond this time, often associated with the onset of right subcostal pain and tenderness, usually indicates development of hepatic necrosis. Liver damage is maximal 3–4 days after ingestion and may lead to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death.
Therefore, despite a lack of significant early symptoms, patients who have taken an overdose of paracetamol should be transferred to hospital urgently.
Administration of activated charcoal should be considered if paracetamol in excess of 150 mg/kg or 12 g whichever is the smaller, is thought to have been ingested within the previous hour.
Acetylcysteine protects the liver if infused within 24 hours of ingesting paracetamol. It is most effective if given within 8 hours of ingestion after which effectiveness declines sharply and if more than 24 hours have elapsed advice should be sought from a poisons information centre or from a liver unit on the management of serious liver damage. In remote areas methionine (2.5 g) orally is an alternative if acetylcysteine cannot be given promptly. Once the patient reaches hospital the need to continue treatment with the antidote will be assessed from the plasma-paracetamol concentration (related to the time from ingestion).
Patients at risk of liver damage and therefore requiring treatment can be identified from a single measurement of the plasma-paracetamol concentration, related to the time from ingestion, provided this time interval is not less than 4 hours post ingestion; earlier samples may be misleading. The concentration is plotted on a paracetamol treatment graph (see Acetylcysteine) of a reference line (‘normal treatment line') joining plots of 200 mg/litre (1.32 mmol/litre) at 4 hours and 6.25 mg/litre (0.04 mmol/litre) at 24 hours. Those whose plasma-paracetamol concentration is above the normal treatment line are treated with acetylcysteine by intravenous infusion (or, if acetylcysteine is not available, with methionine by mouth, provided the overdose has been taken within 10–12 hours and the patient is not vomiting).
Patients on enzyme-inducing drugs (e.g. carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, alcohol, and St John’s wort) or who are malnourished (e.g. in anorexia, in alcoholism, or those who are HIV-positive) may develop toxicity at lower plasma-paracetamol concentration and should be treated if the concentration is above the high-risk treatment line (which joins plots that are at 50% of the plasma-paracetamol concentrations of the normal treatment line).
The prognostic accuracy of plasma-paracetamol concentration taken after 15 hours is uncertain but a concentration above the relevant treatment line should be regarded as carrying a serious risk of liver damage.
Plasma-paracetamol concentration may be difficult to interpret when paracetamol has been ingested over several hours. If there is doubt about timing or the need for treatment then the patient should be treated with an antidote.
Not known to be harmful in pregnancy or breast-feeding.