FDA panel supports return of Vioxx drug

GAITHERSBURG, Md. -- A Food and Drug Administration advisory panel yesterday recommended that Merck & Co. could resume selling the painkiller Vioxx, but must include stringent warnings of the heart problems it can cause and restrictions on its use.

The panel also decided that, like Vioxx, the drugs Celebrex and Bextra pose cardiovascular risks but offer enough benefits that they should remain available -- with warnings and limits similar to those for Vioxx.

The FDA said it would act within weeks on the recommendations but cautioned that does not mean Vioxx would quickly return to the market. FDA officials conceded that the issues before the panel were complex and sifting through their comments will take time. The agency generally follows the panel's suggestions.

The panel's decisions were the culmination of three days of unusual testimony at which some patients made passionate pleas to keep the drugs available while a few asked for more warnings. Medical experts unveiled data showing increased heart risks for some drugs and lesser risks for others, while drug companies defended their products as safe .

For four months, millions of patients who used the painkillers have been unsure about their safety. Merck pulled Vioxx from the market on Sept. 30 after a trial showed it doubled the risk of heart attack and strokes. A flurry of worrisome announcements about other painkillers followed, panicking patients and leaving doctors uncertain how and whether to prescribe the medications.

The panel yesterday, however, did not dismiss those concerns. They said each of the so-called cox-2 inhibiting drugs that include Vioxx, Celebrex, and Bextra also offered benefits that offset risks, when taken at doses low enough.

Of the three drugs, the slimmest vote of confidence by the panel, 17-15, was for recommending the return of Vioxx. Trials showed the drug either raised the odds of heart problems, raised blood pressure, or increased death rates. Many panelists said the lowest dose, 12.5 mg., should be the only one sold and only after people tried safer painkillers. Some suggested patients sign consent forms and undergo regular blood pressure monitoring as a condition of using the drug.

The advisers called for restrictive "black box" warnings to be added to Vioxx's label. The bold warning is the agency's most stringent and would lay out the drug's heart risks. Drugs with black box warnings also have stricter limits on how they can be advertised.

Still, the FDA panel's recommendation was a huge boost for Vioxx, and investors sharply bid up Merck stock. It closed at $32.61 a share, up 13 percent. Shares of Pfizer Inc., which makes Celebrex and Bextra, rose nearly 7 percent to $26.80.

The panel struggled with the heart risks of Bextra. In two trials of patients who underwent complicated heart surgery, risks were evident within 10 days of taking the drug. Many advisers were reluctant, however, to conclude the drug posed the same heart risk for people suffering from arthritis pain. In the end, 17 voted to keep it on the market, while 13 wanted to remove it. Two abstained.

Celebrex, the nation's most popular cox-2 drug, had the weakest evidence of causing heart problems at the 200 mg. dose that most people take. The drug was linked to heart attacks and strokes at four times that dose, however. The vote, 31-1, reflected the panel's confidence in that drug's safety.

The panel recommended that both Celebrex and Bextra carry black-box warnings.

The panel also looked at over-the-counter painkillers that have been on the market for years. The FDA should tailor warnings with the individualized risk posed by each of the older painkillers, advisers decided. But naproxen, found to be neutral or beneficial to the heart, should be free of such warnings, many on the panel said.

Dr. Alastair Wood, the panel's chair, told reporters that naproxen is so safe that people with previous heart problems should take that painkiller first. Given other drugs' risks, a doctor who started a patient with heart risks on a different painkiller would be a "brave man or woman," Wood said.

Besides looking at risks and benefits of drugs currently on the market, the panel directed the FDA on how it should handle cox-2 drugs in the pipeline. Lengthy studies will be required before experimental cox-2 drugs manufactured by GlaxoSmithKline, Novartis and Merck could get approval.

"We learned it the hard way," Dr. Steven Nissen, a Cleveland Clinic cardiologist, told the panel. "Now that we know that, we know where to set the bar for this class of drugs. And it has to be very high."

The guidance on new clinical trials was quite pointed: at least 10,000 patients studied for at least two years to have the statistical confidence that heart attacks and strokes suffered by patients -- a common problem -- aren't caused by the drug.

"That's quite a bit of clarity on a difficult question," said Dr. Robert Temple, the FDA's director of medical policy.

Diedtra Henderson can be reached at dhenderson@globe.com.