Commentary on Acetaminophen

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Abstract
Acetaminophen is being promoted as the preferred analgesic-antipyretic, particularly for pediatric use, with suggestions that it is safer and perhaps more efficacious than aspirin. The claim that acetaminophen is less toxic than aspirin is based on a lower incidence of certain side effects and toxic manifestations observed with acetaminophen than with aspirin. Although in therapeutic doses acetaminophen does not share the adverse gastrointestinal, hemorrhagic, and acid-base side effects of aspirin, it does have its own unique toxicity. When ingested in excessive quantities, it may be more lethal than aspirin, and considerably more difficult to treat. Available studies indicate that acetaminophen and aspirin given in equal milligram doses are equally effective in relieving pain and fever.1,2 In contrast to aspirin, acetaminophen has little anti-inflammatory effect. Animal toxicity studies, although helpful in elucidating mechanisms of toxicity, have failed to provide conclusive answers to the question of relative toxicity of acetaminophen and aspirin. Acute toxicity studies in several animal species have produced widely varying results. The degree of acetaminophen toxicity varies not only among different species3 but also among different strains within the same species.4 Additional determinants of acetaminophen toxicity are the nutritional status5 of the animals and pretreatment with microsomal enzyme inducers or inhibitors6 Furthermore, it is unknown which animal species, if any, best reflect toxicity in humans. A large number of serious acetaminophen poisonings, including fatalities, have been reported from Great Britain during the past decade.7-9 Reports of acetaminophen toxicity have been less common in the United States. However, one major poison control center in the United States recently reported 156 acetaminophen ingestions, with four fatalities, during a one-year period.10

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