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Celecoxib for Patients with Arthritis and Osteoarthritis



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Am Fam Physician. 1999 Jul 1;60(1):293.

The anti-inflammatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is due primarily to inhibition of the enzyme cyclo-oxygenase (COX), a compound required for synthesis of prostaglandins and thromboxanes. Of the two COX isoforms identified, COX-1 is expressed constitutively in most tissues, whereas COX-2 is expressed in the brain, the kidneys and at sites of inflammation. Both isoforms appear in the synovial fluid of patients with arthritis. Older NSAID formulations block both isoforms. Celecoxib, a selective COX-2 inhibitor, has been labeled for treatment of osteoarthritis and rheumatoid arthritis, and in therapeutic doses does not inhibit COX-1. Medical Letter consultants reviewed the data on celecoxib.

Celecoxib is available in 100- and 200-mg capsules and is more expensive than generic diclofenac, naproxen, and ibuprofen. It is rapidly absorbed, reaching peak levels in about three hours, is metabolized in the liver by CYP2C9, and excreted in the feces and urine. CYP2C9 inhibitors, including zafirlukast, fluconazole and fluvastatin, may increase serum concentrations of celecoxib. Because no clinical trials of celecoxib have been published, data about its effectiveness are available from the manufacturer, reports of meetings and U.S. Food and Drug Administration submission logs. Celecoxib taken in dosages ranging from 100 to 400 mg appears to be more effective than placebo and just as effective as 500 mg of naproxen in treating rheumatoid arthritis. However, other trials have shown celecoxib to be less effective than higher dosages of naproxen or ibuprofen in relieving postsurgical dental pain.

Adverse effects include abdominal pain, diarrhea and dyspepsia, and increases in aminotransferase. As with other NSAIDs, renal toxicity has also been reported. However, the incidence of gastrointestinal ulcers is lower than with agents such as diclofenac, naproxen and ibuprofen. Unlike other NSAIDs, celecoxib does not inhibit platelet aggregation or increase bleeding time. Large doses of celecoxib given to pregnant animals decreased fetal survival.

The authors conclude that celecoxib appears to be as effective as older NSAIDs in treating osteoarthritis and rheumatoid arthritis, but it may be less effective as an analgesic for acute pain. Short-term study data indicate that celecoxib is associated with fewer gastrointestinal ulcers than older NSAIDs and does not increase bleeding time. However, whether serious gastrointestinal bleeding will occur less frequently with celecoxib is still unknown.

Medical Letter consultants. Celecoxib for arthritis. Med Lett Drugs Ther. January 29, 1999;4(1045):11–2.

editor's note: The subsequent issue of The Medical Letter stated that celecoxib is also contraindicated in patients allergic to sulfonamides.—b.a.

 

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