Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, naproxen, and related agents are nonselective inhibitors of both cyclooxygenase-1 (COX-1) and COX-2, which catalyze prostaglandin synthesis. This inhibition accounts not only for the analgesic, anti-inflammatory, and antipyretic effects of these agents, but also for side effects such as gastric mucosal damage and renal toxicity. Substantial evidence suggests that sparing COX-1 is advantageous for gastric safety.
This article reviews available information on the new COX-2-selective inhibitor valdecoxib, including its clinical pharmacology, pharmacokinetics, adverse effects, potential drug interactions, and contraindications and warnings. Results of clinical trials of efficacy and tolerability are summarized.
Articles for inclusion in this review were identified through searches of PubMed and MEDLINE (1966-December 2002) and International Pharmaceutical Abstracts (1970-December 2002). Search terms included valdecoxib, Bextra, COX-2-selective inhibitors, coxibs, and selective cyclooxygenase inhibitors. The reference lists of identified articles were reviewed for additional publications. Product information was also obtained from the manufacturer of valdecoxib.
Fourteen clinical studies involving > 4000 patients have been conducted. Valdecoxib was significantly more effective than placebo in the treatment of adult rheumatoid arthritis, osteoarthritis, pain associated with primary dysmenorrhea, and postoperative pain. Valdecoxib was comparable to naproxen for the treatment of rheumatoid arthritis in 1 study and equivalent to naproxen for the treatment of osteoarthritis in other studies. Three studies found valdecoxib comparable to naproxen sodium for the relief of moderate to severe pain due to primary dysmenorrhea, and others found valdecoxib comparable to oxycodone plus acetaminophen and significantly more effective than rofecoxib for the relief of pain associated with dental surgery (P < 0.05). Four safety studies and 2 reviews of clinical trials documented lower rates of endoscopic gastroduodenal ulcer formation with valdecoxib compared with ibuprofen, naproxen, and diclofenac (P < 0.001 to P < 0.05). Valdecoxib did not inhibit platelet function (bleeding time and platelet aggregation) in healthy adults or in the elderly. Due to the risk of potentially serious skin and allergic reactions, patients who are allergic to sulfa-containing drugs should not take valdecoxib. The drug should be discontinued immediately if rash develops.
In clinical trials, valdecoxib was effective for the treatment of osteoarthritis, rheumatoid arthritis, and moderate to severe pain associated with primary dysmenorrhea. As with the other COX-2-selective inhibitors (celecoxib and rofecoxib), valdecoxib appears to produce less gastrointestinal toxicity than conventional nonselective NSAIDs, although some of the relevant clinical studies have been published only as abstracts. Use of valdecoxib should be reserved for patients at risk for NSAID-induced gastrointestinal problems.