phenacetin

Phenacetin, also known as acetophenetidin and N-(4-ethoxyphenyl)acetamide, is an organic compound that was historically used as an analgesic and antipyretic. It is the acetylated derivative of 4-ethoxyaniline (p-ethoxyaniline) and is considered a prodrug, being metabolized in the liver to acetaminophen (paracetamol), which is largely responsible for its pain-relieving and fever-reducing effects. The compound has relatively weak anti-inflammatory activity compared with other analgesics.

Phenacetin was widely marketed in the first half of the 20th century, often in combination preparations with caffeine or other agents. Over time, accumulating evidence linked chronic use of phenacetin-containing medicines to serious health risks, particularly analgesic nephropathy, papillary necrosis, and an increased risk of urothelial cancers. As a result, many regulatory bodies restricted or withdrew phenacetin from human medicines, and it is no longer commonly used in most countries for people.

Chemically, phenacetin is a white crystalline solid that can be prepared by acetylating 4-ethoxyaniline with an acetylating agent such as acetic anhydride. Its withdrawal from widespread medical use has left acetaminophen (paracetamol) as the primary, widely used analgesic and antipyretic derived from the same metabolic pathway, with phenacetin serving mainly as a historical example in discussions of drug safety and regulatory oversight. See also paracetamol.