COX-2 Inhibitors: Bextra Goes, Celebrex Stays
With Vioxx and Bextra both gone, Celebrex is the lone COX-2 drug on the market.
By Donna Rae Siegfried
The Food and Drug Administration (FDA) banged its gavel in 2005, calling for the removal of Bextra (valdecoxib) from the market. Bextra had been one of the two COX-2 inhibitors available after Vioxx (rofecoxib) was withdrawn from the market by its manufacturer in 2004. Now the class of drugs – a subset of the nonsteroidal anti-inflammatory drugs (NSAIDs) designed to be safer on the stomach than traditional NSAIDs – has only Celebrex (celecoxib) in its ranks.
The FDA’s decision to prevent Bextra from being sold countered the recommendation made by the FDA’s Arthritis Advisory Committee during a high-profile, three-day hearing in February 2005. The committee had voted in favor of keeping all COX-2 inhibitors – Bextra, Celebrex and Vioxx – on the market. The FDA’s action – concluding that Bextra’s overall risks outweighed its benefits – came as a surprise to many people with arthritis, as well as to many rheumatologists.
Long-term data regarding cardiovascular safety in people using Bextra was lacking, said the FDA, but short-term data showed that people taking Bextra for postoperative pain following coronary artery bypass surgery had two to three times the risk of heart attack, cardiac arrest, stroke or blood clot in the lung.
That evidence – combined with the fact Bextra already had a “black-box,” a strongly worded and highlighted warning, for a rare-but-serious, possibly life-threatening skin reaction and no better gastrointestinal safety than other COX-2s – led the FDA to decide Bextra had no advantages over other NSAIDs. Pfizer complied by pulling Bextra from the market.
Celebrex is the sole COX-2 now available. The FDA determined that the benefits of Celebrex outweigh potential risks. To keep patients properly informed, the FDA requested that in addition to further studies of Celebrex, the drug’s package insert be revised to include a black-box warning that explains the potential increased risk of cardiovascular problems.
The FDA further concluded that increased risk of cardiovascular problems may be an effect of prescription NSAIDs, such as diclofenac (Cataflam, Voltaren), indomethacin (Indocin), meloxicam (Mobic), nabumetone (Relafen), naproxen (Naprosyn) and others. They asked manufacturers of NSAIDs to add a black-box warning on the drugs’ labels and a medication guide on the drugs’ packaging explaining the potentially serious and life-threatening gastrointestinal, cardiovascular and skin reaction risks. It also includes a reminder to use the lowest effective dose for the shortest period of time.
For over-the-counter NSAIDs, such as ibuprofen (Advil, Motrin), naproxen (Aleve) and ketoprofen (Actron, Orudis KT), the FDA says available studies do not suggest an increased risk of serious cardiovascular events. However, the FDA now requires labels on these products to include more information to better inform patients about potential cardiovascular and gastrointestinal risks and possible skin reactions.
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