Posted on 02/18/2005 3:28:07 PM PST by neverdem
WASHINGTON, Feb. 18 - A federal drug advisory panel unanimously agreed today that the huge-selling painkillers Celebrex, Bextra and Vioxx cause worrisome heart problems, but its members voted to recommend that all three nonetheless be available to patients, accompanied by strong warnings of the risks.
The panel only narrowly supported the continued marketing of Pfizer's Bextra or the return of Merck's Vioxx, voting 17-13 on Bextra and 17-15 on Vioxx. The panel was much more comfortable supporting the continued marketing of Celebrex, favoring the Pfizer painkiller 31-1. The Food and Drug Administration, which has the final word on the regulation of pharmaceuticals, is not obliged to accept the panel's recommendations.
Shares of Merck, which took Vioxx off the market late last year, closed up $3.76, or 13 percent, at $32.61, while Pfizer gained $1.74, or 6.9 percent, at $26.80. Before the hearings, traders feared that the panel might recommend banning all the drugs, which would have been a severe blow to their makers.
Most panelists said that the F.D.A. should place stern warnings on the drugs' labels, ban consumer advertising for the drugs and require that drug makers provide patients with a letter or medication guide outlining the drugs' risks.
Despite the favorable recommendations, the panel's votes were wounding to Pfizer, which had insisted in its presentation to the committee that there was little evidence that either Celebrex or Bextra caused heart problems. The committee greeted many of Pfizer's claims with deep skepticism.
Several panel members said that patients should be urged to first try taking naproxen, sold as Aleve, before taking Celebrex, Bextra or Vioxx. Studies have shown that naproxen does not hurt the heart and may even provide some protection against heart attacks, although naproxen may cause more ulcers than the other drugs.
In each case, the panel's members considered varying data indicating the health risks posed by each medication, but in the end agreed by varying margins that the potential benefits of the pain-killing drugs outweighed the dangers they posed for cardiovascular problems.
But there was debate over how restricted the drugs' use should be. Some committee members suggested that all cox-2 drugs should be "last resorts," while others disagreed or quibbled over what "last resort" meant.
The differing margins in support of the three drugs were in part related to the varying amounts of research available on each. While a majority of the panel narrowly agreed that Bextra, a newer Pfizer pain reliever than Celebrex, should remain on the market, members also acknowledged that less data was available about Bextra's safety.
The panel's recommendations came during the last of three days of hearings at which panel members said they believed that all the cox-2 drugs - which include Vioxx as well as Bextra and Celebrex - carried heart risks.
In December, the F.D.A. said in a statement that data showed higher cardiovascular risks for patients taking 400 milligrams or 800 milligrams a day of Celebrex, and it advised physicians who continued to prescribe Celebrex to choose "the lowest effective dose of Celebrex." The company says that Celebrex is available in 100- and 200- milligram capsules, as well as 400 milligrams.
The panel's assessment of the cox-2 drugs today came just a day after a top research official at Merck, which makes Vioxx, suggested to the federal drug advisory panel that the company might soon decide to resume selling its painkiller in the United States.
The Merck official, Dr. Peter Kim, said that if the panel decided that Celebrex and Bextra, drugs similar to Vioxx, also hurt the heart, "then that would be important to us to take that into consideration with regard to Vioxx."
Dr. Alastair Wood, the chairman of the advisory panel reviewing drugs in a class known as cox-2, asked Dr. Kim what he meant. "Are you saying that if we think that the cardiovascular risk is a class effect, then you would consider putting Vioxx back on the market?" Dr. Wood asked.
Dr. Kim did not answer directly, but said: "The science has progressed. There are unique benefits to Vioxx."
In a statement before today's voting, Merck said, "If the advisory committee and the F.D.A. conclude that the benefits of this class outweigh the risks in some patient populations, then we would have to consider the implications of these new data given the unique benefits Vioxx offers."
Dr. Paul Seligman, a top F.D.A. official, said before the panel's action today that it was too early to determine how the agency would respond if Merck sought to resume Vioxx sales.
The Merck statement was a remarkable disclosure in an already landmark hearing. Panel members have been sifting through studies trying to weigh the risks and benefits of Vioxx, Celebrex and Bextra. None of the drugs cure pain any better than older medicines. They were developed with the hope that they would cause fewer ulcers than older medicines, but Merck withdrew Vioxx in September after a study showed that the drug doubled the risks of heart attack and stroke.
Since then, more studies have shown similar risks for Celebrex and Bextra. The agency called the committee together to tell it what to do. According to much of the testimony, the committee will probably suggest that the drugs stay on the market, with tough warnings about the risks of taking them.
"I don't think any one of us is saying that these drugs should be taken off the market but that they should be used at the lowest safest dose," said Dr. Gary Hoffman of the Cleveland Clinic.
Dr. Michael Domanski of the National Institutes of Health agreed, saying, "It's pretty clear that there is an excess risk confirmed by some or all of these drugs."
The problem, many committee members said, is that patients who are at high risk of developing ulcers are often the same ones who are at risk of heart attacks.
"Finding the sweet spot for these drugs becomes a little bit harder," said Dr. Steven Nissen, a panel member from the Cleveland Clinic. "Older people are at greater risk for gastrointestinal bleeding, and I can assure you that they are greater risk for coronary disease."
Trying to find the right balance between the risks and benefits is the committee's task today. Dr. Wood said that had the advisory panel known about the cardiac risks years ago, it would probably not have voted to approve the drug. But he said something had to be done.
"The number of events that these drugs are going to cause are going to be vastly in excess of anything we've seen before," he said, "so we have to do something."
Several panel members also expressed frustration that the F.D.A. did not have the legal authority to force drug makers to test approved medicines when concerns were presented about their safety.
"I would like to see Congress empower F.D.A. to mandate these kind of trials as these situations occur," said Dr. John Cush, a rheumatologist from Dallas.
Among the most widely anticipated presentations was that of Dr. David Graham, a drug-safety officer for the agency who has sometimes feuded with top agency officials. Dr. Graham suggested that taking high doses of cox-2 drugs hurt the heart even more than smoking, diabetes or high blood pressure.
He said the cox-2 drugs did not seem to have clear benefits to outweigh those risks. The drugs are supposed to cause fewer ulcers than older pain pills, although evidence for that effect has been mixed. Dr. Graham said that 40 percent of those who suffer heart attacks die, compared with 5 percent who suffer serious ulcers. But Dr. Graham also condemned Indocin and Mobic, both popular painkillers.
A study of California Medicaid patients found that Indocin, known generically as endomethacin, nearly doubled the risks of heart attacks in patients, Dr. Graham said.
For Mobic, the risks of heart attack and stroke rose 37 percent, Dr. Graham's study showed. Mobic is manufactured by Boehringer Ingelheim. In the wake of Vioxx's withdrawal and news that Celebrex and Bextra may hurt the heart, sales of Mobic have risen sharply. Dr. Graham suggested that the move toward Mobic was a problem. Several panel members expressed skepticism because the findings were derived from observational studies, which are not completely trustworthy.
Dr. Christopher Grubb, a captain in the Army Medical Corps, said soldiers in the 82nd Airborne were required to carry a cox-2 drug in the event of a battlefield injury. Dr . Grubb said the drugs had allowed many soldiers who otherwise would have been sidelined by pain to be deployed overseas.
The drugs, he said, "are essential for our global war on terrorism." The comment prompted loud laughter in the meeting.
Stephanie Rosenbloom contributed reporting from New York for this article.
The problems with Vioxx occur with long term (months and years) administration. The stuff is very effective for swelling (inflamation) and pain.
Notice that Indomethecin is much more dangerous than Vioxx. Indomethecin (Indocin), valdecoxib (Bextra), meloxicam (Mobic), AND IBUPROFEN (ADVIL, MOTRIN) are all classified as closely related drugs. Advil is more dangerous than Vioxx.
Turns out Vioxx and the other COX-2 inhibitors need a change in prescription guidelines. And that is all.
FReepmail me if you want on or off my health and science ping list.
If I was at risk for cardiovascular disease or stroke and also had to take one of these cox-2 inhibitors for chronic pain, then I would speak with my doc about taking a daily baby aspirin about one hour before any of these drugs or any other NSAID.
I will dig up my post that says the same. Unfortunately the marketing department has overloaded the insurance and the shareholders are going to pay dearly. If they had been honest from the beginning with the information they ALWAYS had, this drug would not have ended up costing them billions. It would have made money. But they just had to sell it to EVERYONE.
The execs that decided to hide and/or ignore the early warnings need to be jailed. That would stop this criminal behavior.
I've read that the drug companies are Cheeseburger Moore's next target along with the FDA. Stuff like this is gonna give him a lot of fodder.
Unfortunately yes. It was all stupidity and greed. The guilty will not pay and the innocents will foot the bill.
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