Another Pain Reliever Pulled

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Another Pain Reliever Pulled
FDA Warns of Risk In Entire Class of Anti-Inflammatories
By Marc Kaufman
Washington Post Staff Writer
Friday, April 8, 2005


Pfizer Inc. reluctantly halted sales of its arthritis painkiller Bextra yesterday after the Food and Drug Administration concluded that the drug posed too many serious safety risks. It was the second major arthritis medication to be withdrawn in the past six months.

In addition to asking Pfizer to stop selling its $1.4 billion-a-year blockbuster, the FDA concluded that the entire class of anti-inflammatory painkillers carries a potentially increased risk of heart attack and stroke -- and it told manufacturers to substantially toughen the safety warnings on almost all nonnarcotic painkillers still on the market.

Prescription painkillers such as Celebrex and Mobic will remain available, but with the strongest safety warnings the FDA can require. The makers of nonprescription pain relievers such as Motrin and Aleve will be required to tell consumers more about their risks -- warning them to take the pills only for the short periods recommended on the labels, usually no more than two weeks.

For millions of pain sufferers, especially people with chronic arthritis, the FDA action was the latest twist in six months of misfortune that began with Merck & Co.'s withdrawal of the popular painkiller Vioxx. Drugs such as Vioxx, Celebrex and Bextra, hailed not long ago as near-miracle therapies, are now either gone or under a cloud, along with dozens of other anti-inflammatory drugs.

"Today's actions protect and advance the health of the millions of Americans who rely on these drugs every day," Steven Galson, acting director of FDA's Center for Drug Evaluation and Research, said in a statement. "FDA is providing the public information based on the latest available scientific data to guide the careful and appropriate use of these drugs."

Yesterday's actions were among the most sweeping ever initiated by the FDA, which has traditionally been reluctant to take drugs off the market and cautious about branding an entire class of drugs as worrisome. Since 1997, the agency has sought the withdrawal of 13 drugs.

The FDA went beyond the recommendations of a 32-member panel of expert advisers that it brought together in February for a three-day public hearing about all nonnarcotic painkillers. That panel narrowly recommended that Bextra should be allowed to remain available and that Vioxx should be allowed back on the market under certain conditions. Galson said that, because the expert panel's votes were so close, the agency believed its actions are consistent with the recommendations.

Alastair J. Wood of Vanderbilt University, the chairman of that committee, applauded the FDA yesterday for "asserting itself and taking a strong stand."

"When a bare minority votes to keep a drug on the market, that's not a safety endorsement -- it's a devastating indictment," Wood said. "The FDA saw that and responded."

By taking Bextra off the market and requiring serious warnings on all other medications in the class known as non-steroidal anti-inflammatory drugs (NSAIDs), the agency will significantly affect the lives of tens of millions of patients in pain who use them. The only major nonnarcotic painkillers not included in the warning are aspirin and acetaminophen (widely sold as Tylenol), which are not NSAIDs but carry different risks of their own.

The speed at which the field of arthritis pain treatment has been transformed left many patients confused and dismayed.

"I don't think that anyone imagined we would be sitting here in April with Vioxx and Bextra gone, with a black-box warning for Celebrex and talking about the safety of NSAIDs that have been used for decades," said John H. Klippel, president of the Arthritis Foundation. "At the moment, the typical person with arthritis is left in a serious quandary."

Klippel said the foundation, which believes authorities have sometimes undervalued the benefits of the painkillers, is nonetheless emphasizing lifestyle changes, injectable medications and some food supplements for arthritis sufferers worried about doing without the pills that gave them relief.

In moving against Bextra, the FDA said it was concerned not only with possible cardiovascular problems but also with potentially fatal skin reactions experienced by a small but troubling number of patients. Galson said Bextra did not pose greater cardiovascular risks than Celebrex, Vioxx or other COX-2 inhibitors -- a subclass of anti-inflammatory drugs -- but had to be withdrawn because it carried the additional heightened skin risk.

Pfizer said that it is suspending Bextra sales in the United States and the European Union at the request of the FDA and European regulators but that it "respectfully disagrees" with the FDA's assessment and wants eventually to resume selling the drug. "For now, patients should stop taking Bextra and contact their physicians about appropriate treatment options," the company said in a statement.

In addition to requesting the withdrawal of Bextra, the FDA said it had asked Pfizer to revise the labeling of Celebrex to include a stern black-box warning and a guide to alert consumers to the increased risk of cardiovascular events, primarily heart attacks and strokes. The agency said it would require black-box warnings on all other prescription NSAIDs and wants manufacturers of similar over-the-counter drugs to include "more specific information about the potential [cardiovascular and gastrointestinal] risks," as well as a warning about potential skin reactions. That request applies to popular nonprescription painkillers containing ibuprofen (sold under brand names such as Motrin and Advil) and naproxen (Aleve).

Wood, the chairman of the FDA expert panel, supports these new warning requirements, but he said they should be different from those on the COX-2 inhibitors.

"We know from the data that Celebrex and other COX-2s carry cardiovascular and other risks, but we don't really know yet that the other non-steroidals do," he said. "They might, and we should be careful as we do more research, but we just don't know yet."

Sen. Charles E. Grassley (R-Iowa), a vocal critic of the FDA, said he was encouraged but remained skeptical of the agency.

"It will be good news if today's action, which goes further than the recommendations of the FDA's advisory panel, is a turning point and indicates a more independent Food and Drug Administration," he said. "What's happened with these painkillers has been a confusing saga for the people who need pain relief, and that can be attributed to systemic failures by the FDA and misplaced priorities of the drug industry."