Liver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g or more paracetamol may lead to liver damage if the patient has risk factors (see below).
If the patient:(a) Is on long-term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes, or(b) Regularly consumes ethanol in excess of recommended amounts, or(c) Is likely to be glutathione deplete, e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, see BNF overdose section.Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however, the imumo protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24 hours from ingestion should be discussed with the NPIS or a liver unit.Caffeine: Symptoms - emesis and convulsions may occur. No specific antidote. However, treatment is usually fluid therapy. Fatal poisoning is rare. If symptoms become apparent or overdose is suspected, consult a doctor immediately.
Very large doses may cause nausea and vomiting. The drug is, however, rapidly metabolised and excreted in the urine. Patients should be kept under observation and treated symptomatically.