Piroxicam (DB00554): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class, first introduced by Pfizer in 1980 under the brand name Feldene.[1] As a small molecule therapeutic, it functions through the non-selective inhibition of the cyclooxygenase (COX) enzymes, COX-1 and COX-2, thereby blocking the synthesis of prostaglandins that mediate pain, inflammation, and fever.[1] Its primary clinical applications are in the symptomatic management of chronic inflammatory conditions, most notably osteoarthritis and rheumatoid arthritis.[4]

The pharmacological profile of piroxicam is distinguished by an exceptionally long elimination half-life, averaging approximately 50 hours.[6] This characteristic allows for the convenience of a once-daily dosing regimen, a significant advantage at the time of its introduction. However, this prolonged duration of action is also a primary contributor to its significant safety concerns. The sustained inhibition of COX-1, an enzyme crucial for gastrointestinal mucosal protection, coupled with its long half-life, elevates the risk of severe gastrointestinal adverse events. Furthermore, its metabolic clearance is almost entirely dependent on the highly polymorphic cytochrome P450 enzyme, CYP2C9, predisposing a subset of the population with reduced enzyme function ("poor metabolizers") to drug accumulation and a markedly increased risk of toxicity.[8]