Acetaminophen overdose

Acetaminophen overdose may occur after an acute single ingestion of a large amount of acetaminophen or acetaminophen-containing medication, or repeated ingestion of an amount exceeding recommended dosage.

Patients are often asymptomatic or have only mild gastrointestinal symptoms at initial presentation. Untreated acetaminophen poisoning may cause varying degrees of liver injury over the 1 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 acetaminophen 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 acetaminophen overdose. The efficacy of acetylcysteine decreases subsequent to the first 8 hours following an acute acetaminophen overdose, with a corresponding stepwise increase in hepatotoxicity with increasing treatment delays beyond 8 hours.

An acute acetaminophen overdose in adults, in terms of FDA-labeled therapeutic dosing, is minimally defined as a cumulative dose of acetaminophen >4 g ingested over 8 hours or less (some authors use a period of 4 hours).[1]Fontana RJ, Liou I, Reuben A, et al. AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury. Hepatology. 2022 Jul 27;00:1–29. https://www.doi.org/10.1002/hep.32689 http://www.ncbi.nlm.nih.gov/pubmed/35899384?tool=bestpractice.com ​

Repeated supratherapeutic acetaminophen ingestion denotes ingestion of excess acetaminophen with intent to treat pain or fever (i.e., without self-harm intent). It may be accidental or intentional. Repeated supratherapeutic ingestion is defined as more than one episode of acetaminophen ingestion over a period greater than 24 hours that results in a cumulative dose of >4 g/day.[2]Dart RC, Erdman AR, Olson KR, et al; American Association of Poison Control Centers. Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2006;44(1):1-18. http://www.ncbi.nlm.nih.gov/pubmed/16496488?tool=bestpractice.com

In adults, hepatotoxicity may occur following ingestion of ≥10 g of acetaminophen in 24 hours. Children are at risk for hepatotoxicity with acetaminophen ingestions ≥200 mg/kg in 24 hours.[2]Dart RC, Erdman AR, Olson KR, et al; American Association of Poison Control Centers. Acetaminophen poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2006;44(1):1-18. http://www.ncbi.nlm.nih.gov/pubmed/16496488?tool=bestpractice.com

The definition of hepatotoxicity after acetaminophen overdose is a serum aspartate aminotransferase or alanine aminotransferase of 1000 international units/L or greater.

Acetaminophen is known as paracetamol in many countries outside the US.