ABSTRACT
Acetaminophen (called paracetamol outside the United States) is a popular and widely used
analgesic and antipyretic agent. First synthesized in 1893, it was introduced for prescription use
in the United States in 1955 and approved for over-the-counter use in 1960 (1). It is frequently
combined with codeine or other analgesic agents, decongestants, and antihistamines. Over 300
different preparations are now available in the United States with more than one billion pills
sold annually. Acetaminophen’s popularity has in part arisen from its apparent lack of side
effects. Unlike aspirin and other nonsteroidal anti-inflammatory drugs, it does not cause gastric
inflammation, ulcers, or coronary ischemia. Although it is remarkably safe when used at usual
therapeutic doses, it has a relatively narrow therapeutic window. Acetaminophen overdose is
the leading cause for calls to Poison Control Centers (O100,000/yr), and accounts for more than
56,000 emergency room visits, 2600 hospitalizations and an estimated 458 deaths due to acute
liver failure (ALF) each year (1). Data from the U.S. Acute Liver Failure Study Group registry of
more than 1100 patients with acute liver failure (ALF) from across the United States, suggests
that acetaminophen poisoning alone currently constitutes nearly 50% of all ALF [Fig. 1; (2)].
Available in single or combination products, acetaminophen produces more than a billion
dollars in annual sales and is heavily marketed for its safety compared to nonsteroidal
analgesics. By enabling self-diagnosis and treatment of minor aches and pains, its benefits
are said by the United States Food and Drug Administration (FDA) to outweigh its risks (3).
