FDA to Weigh Fate of Bextra, Celebrex, Similar Drugs
MONDAY, Feb. 14 (HealthDay News) — When it debuted in 1999, Vioxx was hailed as a wonder drug, even though its advantage lay not in better pain relief but in fewer side effects.
Soon, the drug and others like it in the same class of cox-2 inhibitors became widely prescribed, particularly to arthritis sufferers, thanks to heavy advertising by manufacturers.
Now, the drugs face intense scrutiny over heart risks posed by the medicines. Starting Wednesday, a U.S. Food and Drug Administration (FDA) advisory panel will meet for three days to debate the future of the cox-2s and perhaps even their predecessors, the cox-1s.
At issue is the safety of the drugs. Although originally introduced as a better alternative to traditional nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen and naproxen — all of which increase the risk of gastrointestinal bleeding — recent evidence suggests the cox-2s, as well as naproxen, may elevate the risk of heart attack and stroke.
The billion-dollar blockbuster drug Vioxx fell first, with maker Merck & Co. withdrawing it from the market in September after data linked long-term use to increased cardiovascular risk. Then in December, similar findings surfaced regarding Pfizer Inc.’s Celebrex, although that drug remains on pharmacy shelves. Cardiovascular concerns have also put the spotlight on a popular over-the-counter cox-1 inhibitor, Aleve.
The FDA has ordered a review of trial data on Celebrex and a third cox-2, Bextra. At the same time, the agency is battling critics who contend it has failed to protect consumers from potentially dangerous drugs that were brought to market without sufficient research.
Trying to predict the hearing’s outcome is like reading tea leaves, said Dr. Ira S. Nash, associate director of the Cardiovascular Institute at Mount Sinai Medical Center in New York City.
He conceded, however, that “it’s not inconceivable that they [the FDA] would take one or more of these drugs off the market or put them in a category with black-box warnings — strict statements in the prescribing information about which kinds of patients should not be considered candidates for the drugs.”
There may not be a lot of clear data, though, on which patients should steer clear of the medications, Nash said.
What is clear is that much is at stake.
“Billions of people and billions of dollars,” said Dr. Mark Fendrick, a professor of internal medicine at the University of Michigan School of Medicine and a member of drug maker AstraZeneca’s NSAID advisory board.
“This encompasses issues of multiple organ systems, over-the-counter and prescription drugs. It’s public citizen vs. big pharmaceuticals. This has become a larger-than-life issue about whether the FDA has the necessary tools to ensure drug safety,” he said.
The panel meeting this week will consist of two advisory committees: a committee on arthritis and a committee on drug safety and risk management. All FDA committees are composed of outside experts who are technically independent of the agency.
According to an FDA memo dated Jan. 19, experts will be asked to consider questions of whether there should be continued marketing of cox-2s, whether certain patients might benefit from the drugs in spite of a risk, why the drugs might have these cardiovascular effects and what kinds of trials might be needed to answer these and other questions.
For many, more trials are key.
“We should understand as much as we can before a drug comes to market, but we can’t know everything,” said Dr. Gerard Varlotta, director of sports rehabilitation at New York University Medical Center’s Rusk Institute of Rehabilitation Medicine. “Now, we need to do a controlled study of patients on cardiac medication who voluntarily wish to take the medication [cox-2s].”
“Everything we do in medicine has risk, and we have to discuss and understand the risks,” he added. Cox-1s were left on the market knowing they carried a risk of gastrointestinal bleeding, he pointed out.
Also at issue is the question of pharmaceutical industry marketing.
“Part of the reason why this got to be the problem it did is because the drugs were used quite indiscriminately and that, in my mind, is clearly related to the fact that they were so heavily marketed, both to doctors and to patients,” Nash said. “The marketing of the drugs to patients and to doctors led to uses in groups that, frankly, were far beyond where it was well-studied and beyond groups you would expect to see significant advantages. They were overprescribed.”
The FDA is not obligated to take the advice of its committees, but it typically does.
“The FDA is under a lot of pressure right now because they seem to be behind the curve on this,” Nash said. “It’s just speculation, but one would think that would influence them. I think they’re probably going to err on the side of caution and not want to be seen as either not doing their job or not protecting the public or, even worse, being lackeys for the pharmaceutical industry. So it wouldn’t surprise me if they flexed their muscles a little bit.”
According to Forbes magazine, a briefing document prepared for the panel and released last week was critical of the drugs.
But many doctors, including Varlotta, want the drugs to stay on the market. “The cox-2s are good medications, and before they were around we had a hard time getting patients to tolerate medication.”
“I think it would be a bad outcome if the FDA overreacts and we end up getting to a situation where the drug has to be safe for everybody for it to be used in anybody. That would be a mistake,” Nash added. He also said he thought there should be more details in the prescribing information about who is an appropriate candidate for these drugs and who is not.
Added Fendrick: “I am really hoping that there will be time spent on issues of competing risk between gastrointestinal benefits and cardiovascular risks, that various options for patients with different risk patterns are discussed. Probably a lot of things are going to come out but whether it’s going to be straightforward guidance for physicians and millions of patients who rely on this, all I can do is be optimistic.”
In an early sign that the hearings could prove contentious, U.S. Sen. Charles Grassley, an Iowa Republican, has charged that the FDA is preventing one of its scientists from presenting results from the largest and most recent study of heart risks posed by the cox-2 drugs.
The study was co-written by FDA scientist David Graham, a longtime critic of the medications. It is based on a large California Medicaid database that examined heart risks posed by a wide range of painkillers, including Bextra, Celebrex and Vioxx, the Boston Globe reported Saturday.
This marks the third time in recent months that the FDA has been accused by Congress of ignoring research by its own scientists. In each case, the research was later confirmed by other scientists, the newspaper said.
In a letter to the FDA, Grassley asked why the agency failed to make a review of the California study a priority, “given the urgent regulatory and drug safety issues.”
The letter, sent Friday night to FDA acting commissioner Lester Crawford, demanded a formal reply no later than Wednesday, the day the FDA hearings are scheduled to begin, the newspaper said.
The New York Times reported that an agency spokesman denied that Graham had been barred from presenting his new research. The spokesman told the paper FDA officials had simply expressed a preference “that [Graham] rely on published literature in his talk, but that it was his call if he wanted to offer data from his new study.”
SOURCES: Ira S. Nash, M.D., associate director, Cardiovascular Institute, Mount Sinai Medical Center, New York City; Mark Fendrick, M.D., professor, internal medicine, University of Michigan School of Medicine, and professor, health management and policy, University of Michigan School of Public Health, Ann Arbor; Gerard Varlotta, D.O., director, Sports Rehabilitation, Rusk Institute of Rehabilitation Medicine, New York University Medical Center, New York City~FDA-~~PRES~~SAFE~~HATT~~STRO~