Paracetamol overdose in adults

Overdose may occur after excessive ingestion of paracetamol or paracetamol-containing medication as an acute or staggered overdose, or therapeutic excess.

Patients are often asymptomatic or have only mild gastrointestinal symptoms at initial presentation. Untreated paracetamol poisoning may cause varying degrees of liver injury over the 2 to 4 days following ingestion, including fulminant hepatic failure.

Rarely, massive overdose may initially present with coma and severe metabolic acidosis. Presentation with coma may also occur if a combination preparation of paracetamol and opioid is taken in overdose, or after an overdose of multiple drugs.

Hepatotoxicity is extremely rare in patients treated with acetylcysteine within 8 hours of an acute paracetamol overdose. The efficacy of acetylcysteine decreases subsequent to the first 8 hours following an acute paracetamol overdose, with a corresponding stepwise increase in hepatotoxicity with increasing treatment delays between 8 and 16 hours.

The recommended therapeutic dose of paracetamol depends on age.[1]Ferner RE, Dear JW, Bateman DN. Management of paracetamol poisoning. BMJ. 2011 Apr 19;342:d2218. http://www.ncbi.nlm.nih.gov/pubmed/21508044?tool=bestpractice.com In adults, the maximum dose in 24 hours is 4 g.[1]Ferner RE, Dear JW, Bateman DN. Management of paracetamol poisoning. BMJ. 2011 Apr 19;342:d2218. http://www.ncbi.nlm.nih.gov/pubmed/21508044?tool=bestpractice.com

The National Poisons Information Service (NPIS) in the UK defines different types of paracetamol overdose as follows:[2]National Poisons Information Service. TOXBASE. Paracetamol. 2017 [internet publication]. https://www.toxbase.org/

• Acute overdose: excessive amounts of paracetamol ingested over a period of less than 1 hour; usually in the context of self-harm. 

• Staggered overdose: excessive amounts of paracetamol ingested over longer than 1 hour; usually in the context of self-harm. 

• Therapeutic excess: 

  • Excessive paracetamol taken with intent to treat pain or fever and without self-harm intent. 

  • Paracetamol ingested at a dose greater than the licensed daily dose AND more than or equal to 75 mg/kg/24 hours.

  • Can involve use of excessive doses of the same paracetamol product or inadvertent use of more than one paracetamol-containing product at the same time. 

Doses consistently less than 75 mg/kg in any 24-hour period are very unlikely to be toxic, although risk may be increased if this dose is repeatedly ingested over 2 or more days.

Serious toxicity may occur in patients ingesting more than 150 mg/kg in any 24-hour period. Rarely, toxicity can occur with ingestions between 75 and 150 mg/kg in any 24-hour period. 

The NPIS recommends that, for the purposes of calculating potentially toxic doses, the following be considered:[2]National Poisons Information Service. TOXBASE. Paracetamol. 2017 [internet publication]. https://www.toxbase.org/

• For pregnant patients, the toxic dose is calculated using the patient's pre-pregnancy weight

• For patients weighing more than 110 kg, the toxic dose should be calculated using a maximum of 110 kg instead of the patient's actual weight.

Serious hepatotoxicity after paracetamol overdose is a serum AST concentration >1000 IU/L.[2]National Poisons Information Service. TOXBASE. Paracetamol. 2017 [internet publication]. https://www.toxbase.org/

Paracetamol is known as acetaminophen in some countries.

This topic covers adult patients only. Management of intravenous paracetamol overdose is not covered.