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). In adults, hepatotoxicity may occur following ingestion of ≥10 g in 24 hours. Children are at risk for hepatotoxicity with acute acetaminophen ingestions ≥200 mg/kg in 24 hours. 
The term "repeated supratherapeutic ingestion" (often abbreviated to RSI or RSTI) is used to differentiate chronic overdose from chronic therapeutic use. 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. 
The definition of hepatotoxicity after acetaminophen overdose is a serum AST or ALT of 1000 international units/L or greater.
Acetaminophen is called paracetamol in locations outside of the US.
Associate Professor of Emergency Medicine
University of Colorado School of Medicine
The employer of KH received research grants from McNeil Consumer Healthcare, a manufacturer of acetaminophen.
Staff Specialist in Emergency Medicine
The Prince Charles Hospital
AN declares that he has no competing interests.
Professor Kennon Heard and Dr Alastair Newton would like to gratefully acknowledge Professor Allan R. Mottram, a previous contributor to this topic.
ARM declares that he has no competing interests.
Department of Toxicology
Rocky Mountain Poison & Drug Center
SP declares that he has no competing interests.
Division of Research
Department of Emergency Medicine
Albert Einstein Medical Center
GFOM declares that he has no competing interests.
Department of Medicine
Emergency Physician and Medical Toxicologist
McGill University Health Centre
Centre Antipoison du Québec
SG declares that she is an unpaid co-investigator in the Canadian Acetaminophen Overdose Study and unpaid co-chair of the Extracorporeal Treatment In Poisoning workgroup.
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