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Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis

Michael J Burns, MD
Scott L Friedman, MD
Section Editor
Stephen J Traub, MD
Deputy Editor
Jonathan Grayzel, MD, FAAEM


Since its clinical introduction in 1955, acetaminophen (N-acetyl-p-aminophenol; APAP; paracetamol) has become the most widely used analgesic-antipyretic in the United States [1]. Acetaminophen is a component of hundreds of over-the-counter and prescription medications used worldwide.

Although the drug is considered safe when taken at usual therapeutic doses (up to 4000 mg every 24 hours), overdose of acetaminophen has been recognized since 1966 to cause fatal and nonfatal hepatic necrosis [2,3]. It is suspected that even repeated therapeutic or slightly excessive doses can be hepatotoxic in susceptible individuals, such as alcoholics [4-9]. Acetaminophen is one of the most commonly reported products causing drug-induced liver injury (DILI) [1,3,10,11], and is the most common cause of acute liver failure (ALF) in the United States – accounting for 50 percent of all reported cases and approximately 20 percent of liver transplant cases [12-16].

The pathophysiology, clinical manifestations, and diagnosis of acetaminophen intoxication will be reviewed here. Treatment of this condition and poisoning in children are discussed separately. (See "Acetaminophen (paracetamol) poisoning in adults: Treatment" and "Management of acetaminophen (paracetamol) poisoning in children and adolescents" and "Clinical manifestations and diagnosis of acetaminophen (paracetamol) poisoning in children and adolescents".)


Acetaminophen is widely available, found in numerous products, and people commonly underestimate its toxicity [10]. In addition, a substantial percentage of patients ingest excessive amounts of acetaminophen because they misunderstand dosing directions or fail to recognize that acetaminophen is found in more than one medication they are using [17]. Such errors occur most often among patients with limited literacy or heavy acetaminophen use.

Not surprisingly, acetaminophen remains a major cause of overdose and overdose-related liver failure and death in the United States and many other countries [12,18]. If overdose is identified early enough, mortality rates are extremely low. However, once acute liver failure has developed, morality is approximately 28 percent, and a third of patients require liver transplantation [19]. A national network established in 1998 to track cases of ALF in the United States found that nearly half the episodes of ALF are attributable to acetaminophen [13,20]. Data from this group demonstrate that intentional (suicidal) and unintentional (chronic) poisonings account equally for cases of acetaminophen-associated hepatic failure [13,20].


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