DOCTOR'S VIEW ARCHIVE
Cox-2 Inhibitors After FDA/Arthritis Advisory Committee Meeting February 16-18, 2004 ...Vioxx, Celebrex, BextraMedical Author: William C. Shiel, Jr, FACP, FACR
On February 16-18, 2005, a joint meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee of the FDA Drug Safety Committee ("committee") was convened to review the safety of COX-2 inhibitors including rofecoxib (Vioxx), celecoxib (Celebrex), and valdecoxib (Bextra) NOTE: April 7, 2005, Pfizer has agreed to suspend sales and marketing of Bextra in the U.S., pending further discussions with the with the FDA. For more information, please read the FDA press release. . The committeesreviewed the details of research studies and specifically evaluated the risks of these drugs in regard to heart attack and stroke. They also reviewed other antiinflammatory drugs including naproxen.
Eight of the 32 voting panelists were arthritis specialists (rheumatologists) and the results of the meeting were summarized by the American College of Rheumatology (ACR) as follows:
- A clinical trial using naproxen in patients with Alzheimer's disease noted an increased risk of heart attack and stroke and was halted. According to the advisory panel, the study was stopped because of media attention and not because of an unacceptable safety signal. The data in that study seems to indicate that the numbers were inadequate to come to the conclusion that there was an increased risk of heart attack or stroke in that study. In fact, a number of studies indicated a decrease in the risk of heart attack and stroke when taking naproxen.
- The committee unanimously voted that all of the cox-2 inhibitors significantly increase the risk of heart attack and stroke. The cox-2 inhibitors that are currently on the market in the U.S. are celecoxib (Celebrex) and valdecoxib (Bextra). The committee also agreed unanimously that Celebrex should be kept on the market for its current uses. Regarding Bextra, the committee voted 17 in favor of keeping this drug on the market, 13 not in favor, and 2 abstained.
- The committee agreed unanimously that a "black box" warning should be added to the labeling of each cox-2 inhibitor that would clearly indicate the increased risk of heart attack and stroke. Furthermore, they recommended that this warningadvise that these drugs should be avoided in patients with a high riskfor heart attack or stroke due to the presence of other risk factors.
- The balancing of risks versus benefits of the cox-2 inhibitors favors their continued use.
- While all nonsteroidal antiinflammatory drugs have the potential for causing heart attacks and strokes, the relative risks are not the same. For example, naproxen and Celebrex seem to have less risk than Vioxx or Bextra.
- The risks of heart attack and stroke with cox-2 inhibitors may be greater when the drugs are used in higher doses, for longer periods of time, and in high risk individuals.
- The use of cox-2 inhibitors should be avoided in patients with a high risk for heart attack and stroke due to the presence of other risk factors for heart attack and stroke.
What will happen next?
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The FDA will now review the findings and recommendations of the Advisory Panel. It is expected that the recommendations will be adopted and implemented. If so, there likely will be a tremendous wave of education directed at both physicians and healthcare personnel as well as patients.
A wide variety of clinical research trials will be forthcoming that will further clarify the safety issues of all antiinflammatory medications. Moreover, new antiinflammatory medications will be required to undergo clinical trials that focus on the risks of heart attack and stroke before being marketed in the U.S.
There is a great deal of uncertainty as to whether or not
Vioxx will reenter the U.S. market. If it does, it will certainly carry
"black box" warnings regarding its potential to cause heart attack and stroke.
Reference: American College of Rheumatology, (www.rheumatology.org/hotline)
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