FDA Asks Pfizer to Withdraw Bextra

April 7, 2005
The Food and Drug Administration (FDA) has asked Pfizer to withdraw its COX-2 painkiller Bextra from the market and to include the strongest possible warning on Celebrex. The drugs are similar to Vioxx, withdrawn from the market last year.

Consumer advocates said the FDA's action was too little, too late.

FDA is also requiring stronger warnings on other prescription and over-the-counter painkillers, including Advil, Aleve and other widely-used products (complete list below).

The FDA said the "overall risk versus benefit profile" for Bextra is unfavorable. Merck withdrew Vioxx from the market last September, following indications that it can contribute to serious cardiovascular events including heart attacks and strokes.

Pfizer said it "respectfully disagrees" with the FDA's position on Bextra. Meanwhile, Pfizer said it would also suspend sales of Bextra in the European Union, at the request of European regulators.

"While we are pleased that the FDA has taken Bextra off the market, it has recklessly allowed Celebrex to continue to be sold. An unpublished study finished in 2000 indicated increased cardiac risks associated with Celebrex," said Sidney M. Wolfe, M.D., Director, Public Citizens Health Research Group, who noted that in January, his organization petitioned to have both Bextra and Celebrex removed from the market because they increase the risk of heart attacks.

"Neither Bextra nor Celebrex protects the gastrointestinal tract as drugmakers claim. Given that neither drug has any unique benefits but both carry unique cardiac risks, it is unconscionable to leave Celebrex on the market," Wolfe said.

"We call on Congress, which is finally delving into FDAs operations, to investigate why the agency is not also pulling the equally dangerous Celebrex from the shelves," he said.

Food and Drug Administration safety reviewer David Graham has estimated that Merck's Vioxx may have caused as many as 140,000 heart attacks in the U.S. and the agency undertook a study of the other COX-2 inhibitors, Bextra and Celebrex.

A Merck study showed that patients taking it for 18 months or longer had twice the risk of heart attacks and strokes -- 1.5 percent -- as those taking a placebo.

The study found that Vioxx, given at the standard dose, increases the risk of heart attack by about 50 percent, compared with Pfizer's Celebrex, and more than triples the risk of heart attacks when given at high doses. The two drugs suppress the body's production of the Cox-2 enzyme, which is linked to pain and swelling.

Last October, researchers writing in the New England Journal of Medicine said similar popular drugs of the same class, like Pfizer's Celebrex, could pose similar risks.

Garret A. FitzGerald of the University of Pennsylvania said his research leads him to suspect that Celebrex and other COX-2 inhibitors could have cardiovascular effects similar to those linked to Vioxx. He said clinical trials of all COX-2 inhibitors showed elevated cardiovascular risk, similar to Vioxx.

All COX-2 inhibitors should be viewed as risky and the FDA should "urgently" adjust its policies to "reflect this new reality," FitzGerald wrote.

Vioxx and Celebrex were among the most widely prescribed medications in the United States in recent years. The powerful painkillers made life more comfortable for patients with arthritis and other painful conditions.

"Today's actions protect and advance the health of the millions of Americans who rely on these drugs everyday," said Dr. Steven K. Galson, Acting Director of FDA's Center for Drug Evaluation and Research (CDER).

"FDA is providing the public information based on the latest available scientific data to guide the careful and appropriate use of these drugs aimed at maximizing their potential benefits and minimizing their risks."

Other Painkillers

The FDA is also asking manufacturers of all other prescription and over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) to revise their labels to include the same boxed warning highlighting the potential for increased risk of stroke and gastrointestinal bleeding associated with their use.

FDA also wants manufacturers of over-the-counter NSAIDs to include a warning about potential skin reactions. The labeling of the prescription NSAIDs already addresses potential skin reactions.

COX-2 Selective Non-steroidal Anti-inflammatory Drugs (NSAIDs)andPrescription and Over-the-Counter (OTC) Non-selective NSAIDsApproved Under New Drug Application (NDA) Abbreviated New Drug Application(ANDA)