Epidemiology

Acetaminophen is responsible for over half of all cases of acute liver failure in the US and is the second most common cause of liver transplant worldwide.[11]​ The 2022 Annual Report of the National Poison Data System in the US reported 94,782 single substance exposures to acetaminophen alone, representing a 42% increase when compared with the previous year. In the same report, acetaminophen-containing combination product exposures totaled 27,432 during 2022, an 8.9% decrease from the previous year.[12]​ Exposure cases are defined as actual or suspected contact; for example, ingestion, inhalation, absorption, reported with a substance.

Although a leading cause of liver failure worldwide, acetaminophen is one of the most widely used analgesic and antipyretic drugs.[13]​ Toxicity may occur during self-medication for pain where unintentional “double-dipping” with two acetaminophen-containing products, and misunderstanding the instructions for proper over-the-counter use are common.[14]​ The potential for errors and subsequent adverse events from unintentional misuse is higher among frequent acetaminophen users, those with limited literacy, and patients with dental pain.[14][15][16][17]​​​​ Reports suggest that approximately 6% frequent acetaminophen users unintentionally take more than the recommended dose of 4 g/day at least once a week.[18]

Acetaminophen-opioid combination products increase the risk of hepatotoxicity, both from double-dipping and substance misuse. This finding led the Food and Drug Administration (FDA) to limit the doses of acetaminophen found in combination products, and the US Drug Enforcement Administration to change hydrocodone/acetaminophen from Schedule III to Schedule II. Subsequent to these changes, the rates of combination product overdoses may be declining.[12][19][20]

Acetaminophen is one of the most frequently used drugs in intentional overdose, particularly in young people, and has historically accounted for similar proportions of acetaminophen-induced liver failure cases as unintentional chronic poisoning.[21][22][23]​​

Pediatric patients may be at unique risk for therapeutic excess of acetaminophen due to miscommunication amongst caregivers (e.g., timing of last dose or number of doses in a day), discomfort with the recommended exclusive dosing for pediatric liquid medications (which is typically dosed in milliliters rather than milligram), and use of nonstandard tools (e.g., kitchen spoons) for medication administration.[24][25][26][27]​​​​

There are rare case reports relating to iatrogenic acetaminophen poisoning following intravenous administration of acetaminophen in both the adult and the pediatric population.[28][29]

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