Safety profiles of leading nonsteroidal anti-inflammatory drugs

Recently introduced nonsteroidal anti-inflammatory drugs (NSAIDs) have capitalized on new formulations or unique physical and pharmacologic properties in an attempt to provide a greater margin of gastrointestinal (GI) safety. The use of enteric coatings and nonoral or pro-drug formulations have not necessarily provided the expected safety, but other properties have been identified that appear to be more promising. However, as demonstrated by oxaprozin, considered to be one of the least safe NSAIDs but one of the leading drugs on the US market, success may not be dependent on safety. In contrast, the improved tolerability of 2 other new NSAIDs, nabumetone and etodolac, has been established in clinical trials and limited postmarketing surveillance. This improved tolerability is probably associated with several pharmacologic properties that have been suggested to contribute to GI safety: (1) nonacidic pro-drug formulation; (2) lack of enterohepatic recirculation; (3) a short plasma half-life; and (4) preferential inhibition of cyclo-oxygenase-2 (COX-2). Although these factors may not improve efficacy, their incorporation into the design of drugs suggests that safer NSAIDs may be a clinical reality. However, the safety and clinical value of any new drug for the general population will be validated only through extensive postmarketing surveillance.