Rofecoxib, a selective COX-2 inhibitor, has been approved by the FDA for treatment of osteoarthritis, acute pain and menstrual pain.

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Increasing use of rofecoxib (Vioxx) and celecoxib (Celebrex), both selective inhibitors of cyclooxygenase-2 (COX-2), for treatment of arthristis has been accompanied by concerns that they may increase risk of thrombotic cardiovascular events.

Rofecoxib (Vioxx - Merck) has been withdrawn from the market due to an increased risk of cardiovascular complications associated with its long-term use. The question remains whether all selective COX-2 inhibitors carry the same risk. Full-page advertisements in newspapers for celecoxib (Celebrex - Pfizer), the most widely used COX-2 inhibitor, assure the public that it does not.

Valdecoxib (Bextra - Pharmacia/Pfizer), a selective cyclooxygenase (COX-2) inhibitor similar to celecoxib (Celebrex) and rofecoxib (Vioxx), was recently approved by the FDA for treatment of osteoarthritis, rheumatoid arthritis and primary dysmenorrhea.

Low-dose aspirin is widely used as an antiplatelet drug to reduce the risk of cardiovascular disease (Medical Letter 2000; 42:18). Recent reports suggest that the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen (Motrin, and others) may decrease the efficacy of aspirin for this indication. The manufacturer of Tylenol is capitalizing on these reports by advertising that aspirin-taking patients who need pain relief should use acetaminophen instead of ibuprofen.

The FDA has authorized two manufacturers (Teva, Mylan) to market generic formulations of celecoxib (Celebrex – Pfizer), the only COX-2 selective inhibitor remaining on the US market. Celecoxib is less likely than nonselective NSAIDs to cause gastric ulcers or other GI toxicity,1 and unlike traditional NSAIDs, it does not have an antiplatelet effect.Celecoxib is much less COX-2 selective than rofecoxib (Vioxx), which was removed from the US market because of an increased risk of cardiovascular events. One analysis of randomized clinical trials that included a total of about 26,000 patients...

Meloxicam, a nonsteroidal anti-inflammatory drug (NSAID) with some cyclooxygenase-2 (COX-2) selectivity in vitro, has been approved by the FDA for treatment of osteoarthritis.

Selective COX-2 Inhibitors and Bleeding Risk: An Additional Note - The Medical Letter article on Drugs for Pain (August 21, 2000) stated that the selective COX-2 inhibitors celecoxib (Celebrex) and rofecoxib (Vioxx) do not inhibit platelet aggregation or bleeding time. Perhaps we should have added, as we did in discussing use of these drugs in rheumatoid arthritis (July 10, 2000), that both celecoxib and rofecoxib, if given with warfarin (Coumadin, and others), increase INR and prothrombin time values and may increase the risk of bleeding.

The results of a clinical trial (PRECISION) comparing the cardiovascular safety of the COX-2 selective NSAID celecoxib (Celebrex, and generics) with that of ibuprofen and naproxen, which are nonselective, have been described in the lay press in terms that may overestimate the safety of celecoxib.

With the removal of Vioxx from the market and concerns about cardiovascular toxicity with other selective COX-2 inhibitors, patients are looking for safe alternatives, and manufacturers of other drugs are looking for additional market share. The COX-2 inhibitors first became popular because they have less upper GI toxicity than older less selective NSAIDs, at least in the short term, in patients not taking aspirin.