FDA panel OKs availability of 3 painkillers

Heart attack, stroke risks noted, but so are benefits

Agency decision due in weeks

Critics say Cox-2 drugs too dangerous for sale

February 19, 2005|By David Kohn | David Kohn,SUN STAFF

GAITHERSBURG - An influential Food and Drug Administration advisory committee concluded yesterday that three controversial anti-inflammatory drugs increase heart attacks and strokes, but recommended that the medicines remain available because of their benefits.

The decision pleased the drugs' makers but disappointed some researchers and public health advocates, who said that at least two of the three painkilling drugs, which are known as Cox-2 inhibitors, are too dangerous to be on the market.

The medications, Vioxx, Celebrex and Bextra, have been at the center of a controversy over drug safety since at least September, when Vioxx manufacturer Merck & Co. withdrew it from the market after a study showed it raised cardiovascular risks. Since then, several studies have seemed to confirm the hazards, and other research implicated the other two Cox-2 inhibitors. In response, some critics have called for the FDA to remove Celebrex and Bextra from the market or severely limit their use.

The most unexpected vote was the decision on Vioxx, which Merck had said Thursday it would consider returning to the market depending on the panel's decision.

"I am surprised. We discussed study after study," said Dr. Gurkirpal Singh, a senior researcher at Stanford University who worked on a key study that uncovered problems with Vioxx and who testified this week before the committee. "But at the time of the vote, the data didn't seem to make a difference."

Advice usually adopted

The committee's recommendations are not binding, but the FDA usually adopts advisory panel findings. Dr. John Jenkins, director of the FDA's Office of New Drugs, said the agency was "committed to making a decision in the next several weeks."

The committee, a combination of two other FDA advisory committees on drug safety and arthritis drugs, agreed almost unanimously that all three drugs significantly increase cardiovascular risk. There was little debate over whether to allow Celebrex to remain on the market. But for the other two drugs, there was wide disagreement over whether they should be marketed in the United States.

The panel voted 17-13 to support continued marketing of Bextra, with two abstentions, and 17-15 in favor of Vioxx.

The most contentious debate concerned Bextra. Several researchers, including the committee chairman, Vanderbilt University professor of medicine Alastair Wood, argued that the available evidence strongly suggested that the drug was too risky. But others countered that compared with Vioxx, little research had been done on Bextra's cardiovascular hazards. The evidence against Bextra rested largely on research that found the drug increased serious heart problems in patients who had recently had bypass surgery.

Others countered that ignorance was not a good argument for allowing continued sales. "Lack of evidence is not a good reason for leaving it on the market," said Curt Furberg, a public health specialist at Wake Forest University.

The first Bextra vote was 15-7 in favor of allowing it to stay on the market, with 10 members abstaining, apparently unable to make up their minds. But after one member, Dr. Steven Nissen, criticized the abstainers for not having the courage to choose, another vote was taken. This time, only two abstained.

Jenkins said that when making its decisions, the FDA would take into account the close votes on Vioxx and Bextra. He said the agency would focus not only on the votes, but on the extensive comments made by those on the committee.

Many who voted to allow the drugs to stay on the market did so with reservations, recommending that use be restricted to low-risk patients and that drug labels include strong warnings about possible hazards.

Black box label

Many suggested that the agency include a so-called black box label for the drugs, a prominent warning on the medicine's packaging that also limits how drug makers can market the product.

Another common recommendation was for the agency to limit direct-to-consumer advertising, which some critics have said encouraged use of the drugs by patients who didn't really need them.

The committee also debated whether to extend warnings to other painkilling drugs. Recent evidence has suggested that other drugs in this category, including nonsteroidal anti-inflammatories such as naproxen, might also pose some cardiovascular risk. Many of these drugs also inhibit Cox-2, an enzyme involved in inflammation.

Decreasing Cox-2 seems to increase clotting and might increase other cardiovascular risk factors. Some members suggested putting warnings on many of these drugs, but others argued that this step would confuse and worry consumers.

After yesterday's decisions, Merck released a brief statement saying that it looked forward to discussions with the FDA.

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