FDA Gives Bextra the Boot
April 08, 2005
By: Jean Johnson for Shoulder1
The Food and Drug Administration (FDA) has requested that Pfizer, Inc. voluntarily withdraw the arthritis drug Bextra from the market on the basis of inadequate data on cardiovascular safety and possible skin complications. At the same time the FDA is mandating that increased warnings appear on the packaging of all prescription and over-the-counter NSAIDs or non-steroidal anti-inflammatory drugs.
Controversy is nothing new for the class of drugs into which Bextra falls – Cox-2 inhibitors that came onto the market in 1998 and 1999. Cox-2 drugs appeared with great acclaim and promises to resolve stomach problems patients experienced relieving arthritis pain with longterm use of Ibuprofen (Advil), Naproxen (Aleve), and aspirin. Still there is good reason for their use according to associate professor and medical director of the rheumatology clinic at Oregon Health & Sciences University, Atul Deodhar M.D.
“In 1997 an estimated 16,500 died in the United States from gastrointestinal bleeding. Compare that to 16,800 that died of AIDS that same year,” said Deodhar. “While HIV is well-publicized, people don’t realize how big this problem of GI bleeding is. That’s why when the Cox-2 drugs came out everyone was excited.”
“Then it started to dawn on people that because of the way Cox-2 drugs work, clotting isn’t prevented and so problems with heart attack and stroke could occur,” Deodhar continued. “So there were a number of studies of 8000 people each in which Celebrex and Vioxx were evaluated. Because Bextra didn’t come out until 2000, it was not subject to these early investigations.”
Deodhar explained that after data alerted Merck to problems with Vioxx, the company pulled the drug voluntarily. “Bextra is similar to Vioxx and clotting associated with both drugs increased the risk for heart problems significantly,” said Deodhar. “But Pfizer never pulled out and kept saying ‘our drug is safe.’”
Even though Celebrex is a Cox-2 inhibitor drug as well, numerous studies it has been subjected to “do not show a major signal that it can cause heart attacks,” Deodhar said. “However, because as a Cox-2 inhibitor there is a theoretical concern, we don’t want to be caught wrong footed and that’s why the FDA has recommended the big black box warning.”
Celebrex has been on the market six years and has been used by hundreds of thousands of patients. Thus in addition to initial formal studies, there have been numerous observational studies in groups throughout the US and Canada like Kaiser Permanente in California and Medicaid in Tennessee. “That’s why I continue to use Celebrex even though six to eight months ago I had our staff pull all the Bextra samples from the rheumatology clinic,” Deodhar said. “Since the drugs treat the same problem, I couldn’t find any reason to use Bextra. Like Vioxx there were potential problems with high blood pressure and heart disease.”
Chairman of the rheumatology department at the Ochsner Clinic Foundation in Baton Rouge, Stephen Lindsey M.D., disagrees. “We believed what we heard six weeks ago when the advisory panel recommended to the FDA that they were not going to remove these medications from the market,” Lindsey said. “It puts the physician is a funny position. One day, you’re telling patients one thing and the next you’re telling them something 180 degrees different.”
Deodhar, however, observes that the vote from the advisory panel that makes recommendations to the FDA was very close with 17 voting yes, 13 no, and two abstaining. “My reaction is that the FDA works,” said Deodhar. “I think it’s good that they are not jumping to conclusions and bending to pressure from lawmakers and the public. Instead they are doing proper studies and making proper decisions.”
In addition to removing Bextra from the market, the FDA has asked Pfizer to add warnings on Celebrex alerting patients to potential risks. The federal office will also request that manufacturers of all prescription drugs containing NSAIDs to warn patients of potential risks for serious or life-threatening cardiovascular and gastrointestinal risks. And even though available data do not appear to suggest an increased risk of serious heart and stomach events over the short term, the FDA will also ask manufacturers of all over-the-counter products containing ibuprofen, naproxen, and ketoprofen to revise their labels to that consumers are alerted to both potential heart and stomach risks as well as the need to seek a physician’s advice when using the drugs.
The FDA, then covered its bases. With hundreds of thousands of patients taking Cox-2 inhibitors and millions more of us with ibuprofen in the bathroom medicine chest at home, the federal government most likely thought prudence best and a forewarned public most able to make informed decisions.
Last updated: 08-Apr-05