Comparative safety evaluation of non-narcotic analgesics

Both spontaneous reports and single outcome studies may distort the overall safety evaluation of drugs. We identified epidemiologic studies, published from January 1970 to December 1995, that investigated the association of s erious adverse effects with aspirin, diclofenac, acetaminophen, and dipyron e to determine and compare the excess mortality associated with short-term drug use. The estimated excess mortality due to community-acquired agranulo cytosis, aplastic anemia, anaphylaxis, and serious upper gastrointestinal c omplications was 185 per 100 million for aspirin, 592 per 100 million for d iclofenac, 20 per 100 million for acetaminophen, and 25 per 100 million for dipyrone. The estimates were largely influenced by the excess mortality as sociated with upper gastrointestinal complications. A relative risk estimat e of 300 or more for the association of dipyrone with agranulocytosis would have been necessary for the excess mortality of dipyrone to be comparable to that of aspirin or diclofenac. Based on published epidemiologic evidence used to determine the excess mortality associated with short-term use of t hese four non-narcotic analgesics, the current regulatory ranking of the dr ugs appears inappropriate. J CLIN EPIDEMIOL 51;12:1357-1365, 1998. (C) 1998 Elsevier Science Inc.