Tens of millions of users of Motrin, Aleve, Celebrex and other painkillers should be given more information about their risks, such as heart attacks or ulcers, the Food and Drug Administration said yesterday.
In a sweeping safety action, regulators in the United States and Europe also asked Pfizer Inc. to withdraw its prescription pain reliever Bextra, saying it could do more harm than good compared with other drugs.
The FDA’s actions on both prescription and nonprescription drugs sent its strongest sign yet of a change in agency tone on safety. It began from a controversy over one drug, Vioxx, which Merck & Co. Inc. voluntarily withdrew in September.
The failure of Vioxx rattled the industry, raised questions about the FDA itself, and sent millions of patients scrambling for different medications.
That, in turn, led to safety questions about other drugs, some of which, such as ibuprofen, have been used for decades in a business worth hundreds of billions of dollars.
Bextra’s withdrawal also could spawn a wave of product-liability cases involving the drug, long criticized by some health advocates.
“Finally, it’s buried. And that’s a good thing,” said Eric Topol, a researcher at the Cleveland Clinic Foundation and a Vioxx critic.
“Today’s actions protect and advance the health of the millions of Americans who rely on these drugs every day,” Steven K. Galson, acting director of the FDA’s Center for Drug Evaluation and Research, said in a statement.
The FDA lists nearly 50 drugs or drug combinations as “nonsteroidal anti-inflammatory drugs,” or NSAIDs, including the prescription drugs Celebrex and Bextra.
The over-the-counter, or nonprescription, drugs include Motrin and Advil (both ibuprofens), Aleve (naproxen), Mobic and Diclofenac.
Excluded from the list are aspirin and acetaminophen, also known as Tylenol.
“The FDA is asking the manufacturers of all over-the-counter NSAIDs to revise their labels to include more specific information about the potential cardiovascular and gastrointestinal risks,” the FDA statement said, adding that skin reactions were also a risk.
The FDA did not spell out the basis for its concerns about the drugs yesterday. It also was vague on the specific wording of the warnings, saying only that they would differ depending on whether the drug is sold by prescription or over the counter.
“We plan to develop our proposed text for the new labeling in the next few weeks, and will request that each sponsor adopt that text,” said John Jenkins, an official in the FDA’s Office of New Drugs.
Some experts, while expressing skepticism about the impact of labels, praised the FDA’s new stance on drug safety.
“It may be helpful if it gets people’s attention not to exceed the over-the-counter dose,” said Alastair J.J. Wood, a professor at Vanderbilt University Medical School and chairman of the FDA’s arthritis panel.
Reaction was mixed among customers at a CVS store on Chestnut Street in Center City.
“I would still take them, even with a warning,” said Linda Tripp, 59, of West Philadelphia, who said she used Advil for knee pain. “They have given me two and a half to three hours of slow relief.”
But Tanya Thompson, 52, of North Philadelphia, said she read the labels and tried to heed them. “Let them put warnings on everything,” Thompson said. “It’s up to the consumer to decide whether to use it.”
The FDA took the action almost seven weeks after its own panel of advisers recommended that the prescription drugs Bextra, Celebrex and Vioxx all known as Cox-2 inhibitors were safe enough to remain on the market.
However, the panel’s vote had been close on Bextra and Vioxx, leading to speculation that the FDA might rule against them.
“This didn’t surprise me a bit, and I’m a bit relieved,” said Wood, who had voted against letting Bextra stay on, and Vioxx return to, the market.
All three drugs were designed to relieve pain without the older drugs’ risks of gastrointestinal side effects, such as ulcers and internal bleeding. However, studies have found that the newer drugs carry higher risk of heart attack or strokes, or kidney and skin problems.
The FDA said it had asked Pfizer on Wednesday evening to cease selling Bextra after it concluded that the drug’s risk of heart and skin reactions exceeded its benefits compared with other drugs on the market.
“Patients currently taking Bextra should contact their physicians to consider alternative treatments,” the FDA said in a statement yesterday.
Hours later, European regulators contacted Pfizer and asked it to suspend sales of Bextra in the 25-nation European Union, according to Pfizer. It was unclear whether the FDA and European Union had coordinated their actions.
In its statement, Pfizer disputed the regulators’ logic but said that, “in deference to the agency’s views, the company has agreed to suspend sales of the medicine pending further discussions with the FDA.”
Bextra was Pfizer’s seventh-best-selling drug last year, with sales of $1.24 billion, but its sales have fallen.
The FDA let Pfizer keep Celebrex on the market but asked it to include more safety data about heart and stroke risks and insert a detailed Medication Guide for physicians.
Pfizer readily agreed and said it would “add expanded risk information.”
Celebrex was Pfizer’s No. 3-selling drug, with $2.78 billion in sales last year. But despite Pfizer’s efforts to shield it from Vioxx-related fears, Celebrex sales have plunged.
Sidney M. Wolfe, director of health research at the advocacy group Public Citizen, faulted the FDA for not going far enough. “While we are pleased that the FDA has taken Bextra off the market, it has recklessly allowed Celebrex to continue to be sold.”
Consumers Union also called for more action. “Removal of a dangerous drug from the market is a good thing, but it leads to the larger question: Why were these unsafe drugs being sold in the first place?” said Jeannine Kenney, senior policy analyst. “The FDA badly needs reform of its reactive, passive drug-safety system.”
The FDA said no decision had been made yet on relaunching Vioxx, an option Merck raised during the advisory meeting. The agency said it would “carefully review” any new Merck application.
Merck said in its statement that it “respects the FDA decision” on Bextra and “looks forward to discussions with the FDA.”
“Clearly, they want to take a second look, very careful look,” at Vioxx before letting it back on the market, said Louis Morris, a former FDA official and now an industry consultant, who also was on the FDA panel.
Several experts said the Bextra withdrawal boded ill for Vioxx’s return. “The hurdles are so high now. There’s no chance,” Wood said.