Pfizer takes drug Bextra off marketAs Pfizer Inc. removed the painkiller Bextra from the market yesterday under pressure from the FDA, the government said almost all of the nation's popular anti-inflammatory drugs carry potential risks of heart attack and stroke when used in high doses over long periods.
In a sweeping public health advisory, the Food and Drug Administration said it wants manufacturers to include stronger warnings on the packaging of painkillers ranging from staples such as ibuprofen and naproxen to newer drugs such as Celebrex.
Prescription strength versions of the drugs will include so-called "black box" warnings, the FDA's strongest, in the labels that physicians and pharmacists see.
Prescriptions also will be dispensed with FDA-approved language listing the risks, which include gastrointestinal bleeding as well as serious cardiovascular problems.
Some experts praised the agency's relatively swift action, less than two months after an advisory panel identified significant cardiovascular risks among newer-generation drugs including Bextra. The panel recommended that the agency limit the drugs' use.
It will be some time, however, before the warning language is vetted and shows up on the packages of non-steroidal anti-inflammatory drugs, known collectively as NSAIDs.
Many experts said the FDA had made the right choice in asking Pfizer Inc. to pull Bextra. But patients and physicians alike struggled to make sense of a blanket warning that covered 19 drugs, sold under dozens of brand names, but provided no guidance on which ones to take.
"The entire world of prescribing non-steroidal anti-inflammatories has now been turned on its head," said Dr. Thomas Lansdale, an internist and chair of medicine at Greater Baltimore Medical Center.
The FDA advised patients to seek their doctors' advice and emphasized that short-term use of over-the-counter strength versions of the medicines does not appear to pose the same risks.
Dr. Steven Galson, acting director of the FDA's Center for Drug Evaluation and Research, said the agency asked Pfizer to withdraw Bextra because it appeared to be associated more frequently with potentially life-threatening skin reactions than its competitors without showing additional benefits.
The decision marks the second time in seven months that a manufacturer has voluntarily pulled a blockbuster anti-inflammatory from the market. Merck & Co. withdrew Vioxx in late September after identifying an increased risk of heart attack and stroke.
Vioxx, Bextra and Celebrex are among a once-heralded group of painkillers known as Cox-2 inhibitors, which work by suppressing the Cox-2 enzyme associated with inflammation.
The drugs first appeared on the market in 1998 and became hits because they reportedly caused fewer gastrointestinal problems than older anti-inflammatories such as ibuprofen and naproxen.
The FDA advisory issued yesterday encompassed almost all NSAIDs, including Bextra and Celebrex. The exception was aspirin - which has been shown to reduce the risk of cardiovascular problems.
The withdrawal of Bextra leaves only one new Cox-2 inhibitor on the U.S. market - Pfizer's Celebrex.
Yesterday's action isn't likely to end the debate over the drugs' safety. The discussion has raised broader issues of the FDA's effectiveness, sparked a movement for better after-market monitoring, and led to congressional hearings.
Yesterday, the FDA said that in addition to requiring new warnings, it has asked manufacturers to review data from previous clinical trials and submit it for FDA analysis. It is not requiring new trials, although Pfizer has agreed to a further study of Celebrex.
Pfizer issued a statement saying it "respectfully disagrees" with the FDA's conclusion about Bextra and wants to talk with the agency about how it can bring back a drug that logged $1.2 billion in sales last year. The company's stock gained 4 cents yesterday, closing at $26.90.
Yesterday, Merck also expressed interest in continued discussions with the FDA. Its drug Vioxx posted sales of more than $1.3 billion in 2004. Merck's shares gained 60 cents yesterday, closing at $33.49.
Some experts praised the FDA for responding quickly to the recommendations of its advisory committee, which met in late February. Some were surprised that the FDA's actions seemed more aggressive than the panel had asked for.
"This is an unprecedented action. To get the recommendations out six weeks after the meeting tells me they've been working very hard," said Dr. Steven Nissen, a cardiologist at the Cleveland Clinic and a member of the panel. He noted that when the panel made recommendations about Vioxx in 2001, the agency did not act for more than a year.
At its February meeting, the advisory committee voted 17 to 13 to keep Bextra on the market. Nissen was among the majority at the time, but yesterday he backed the FDA's decision. Had he known more about Bextra's increased risk of severe skin reactions, he would have voted differently, he said.