FDA panelists stop short of removing pain killers from market
Stronger warnings, patient information recommended for the drugs
A joint U.S. Food and Drug Administration (FDA) advisory panel has allowed three cyclooxygenase-2 (COX-2) inhibitors — two narrowly — to remain on the market.
The FDA held a meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee to discuss the overall benefit-to-risk considerations (including cardiovascular and gastrointestinal safety concerns) for COX-2 selective nonsteroidal anti-inflammatory drugs and related agents in February. The panelists unanimously agreed that COX-2 inhibitors significantly increase the risk of heart attacks and strokes, and some panelists preferred naproxen (Aleve) with a proton pump inhibitor as first-line therapy over COX-2 inhibitors.
All but one of the 32-member panel voted in favor of Pfizer’s continued marketing of celecoxib (Celebrex). Although this vote may seem like an endorsement, the committee wanted more strongly worded warnings in place, such as black-box warnings and patient education materials. The panel also talked about banning direct-to-consumer advertising and about the side effects of doses more than 200 mg.
The panel was much more divided on the other COX-2 drugs. The vote for the continued marketing of rofecoxib (Vioxx) was 17-15. Merck had voluntarily removed rofecoxib from the market in September after a study showed it doubled the risk of heart attacks and stroke. A company spokesperson implied to the FDA panel, however, that it might make the drug available again.
The panel discussed adding the strongest black-box warnings for rofecoxib, as well as banning direct-to-consumer advertising. Some members recommended rofecoxib be given as second- or even third-line therapy, dosing be cut to 12.5 mg, and patients be required to participate in some sort of informed consent process.
The vote for the continued marketing of valdecoxib (Bextra) also was close, 17 to 13 with two abstentions. Some panel members questioned the paucity of data regarding this drug. "Absence of data is important here, I think, particularly in the presence of a safety signal, a strong safety signal," says Alastair J.J. Wood, MD, the meeting chair and an associate dean and professor of medicine and pharmacology at Vanderbilt Medical School in Nashville, TN.
The panelists thought valdecoxib should have stronger warnings than celecoxib and wanted to stop direct-to-consumer advertising. Some panelists expressed concern over adverse skin reactions and wanted the drug contraindicated in cardiac surgery.
Lessons from the meeting
One lesson from the rofecoxib market withdrawal and the subsequent meeting is that every drug needs to be evaluated, because none is risk-free, says Will Rowe, executive director of the American Pain Foundation in Baltimore.
"Many of us knew that, but the public awareness was not there," he says. "This does make it clear."
Another lesson is that drugs are very individualized, Rowe continues. "When considering a prescription for any condition — we are talking here about pain and the risk profiles connected to these medications — pharmacists and other health care practitioners need to be well aware of the risk profile of the patient."
The foundation contends that patients need to have the information and education about their own profile, their own risk, and the medicines that are prescribed for them, he says. "Clearly, those in the circle of care, namely physicians, nurses, and pharmacists, need to have that same information, and there needs to be open discussion about risks and individual profile. The role of the pharmacist is to be more cognizant about the risks associated with the medicines along with the risk profile of the patients receiving them."
One recent controversy stemming from the meeting was that 10 of the 32 panelists who endorsed the continued marketing of the celecoxib, rofecoxib, and valdecoxib have consulted in recent years for the companies that make the drugs. According to a New York Times story that was widely publicized, the committee would have voted 12-8 that valdecoxib should be withdrawn and 14-8 that rofecoxib should not return to the market if the 10 advisers had not cast their votes. The 10 advisers with company ties voted 9-1 to keep rofecoxib on the market and 9-1 for rofecoxib’s return.
Rowe doesn’t concern himself with this controversy. "It’s really the science that is important on our end," he says.
A joint U.S. Food and Drug Administration (FDA) advisory panel has allowed three cyclooxygenase-2 (COX-2) inhibitors two narrowly to remain on the market.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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