Recommendation Made Despite Concerns That Diabetes Drug Boosts Heart Attack Risk
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Experts overwhelmingly expressed confidence that the drug, also called rosiglitazone, boosts the risk of heart attack and other dangerous heart problems. But they then voted 22-1 to urge the FDA to allow continued sales to U.S. patients.
But those continued sales are likely to carry significant new warnings about who can safely use Avandia. Several experts said the FDA should consider either stark new "back box" warnings on Avandia or other restrictions that could limit its availability in patients with heart disease.
"We certainly sent I think a clear signal that there's going to be changes in the way this is promoted ... and certainly in how physicians use this drug," Clifford Rosen, MD, the panel's leader, said after the decision.
The decision came despite calls from some FDA officials to pull Avandia from the U.S. market.
"A wrong decision will cost thousands of lives," said David Graham, MD, an FDA safety officer who urged Avandia be removed.
But officials from GlaxoSmithKline, Avandia's manufacturer, pointed out that no studies had shown that patients taking Avandia were more likely to die of heart problems than those taking another drug or a placebo.
"These data tell us that those events aren't resulting in excess mortality," said Ronald Krall, MD, the company's chief medical officer.
Keeping Options Available
Experts ultimately said they were worried about taking Avandia away as an option for patients when it is still possible that many may benefit from it.
"To perform a draconian type of operation on this medication probably would not be advisable in the long run, said David S. Schade, MD, a professor of medicine at the University of New Mexico School of Medicine and a member of the advisory panel.
Avandia is an oral medication used by patients with type 2 diabetes to help control blood sugar. Millions of patients have taken Avandia, as well as a similar drug called Actos, or pioglitazone.
But Monday's decision comes after three studies each concluded that Avandia boosted the risk of heart attacks and other cardiovascular problems by 30% to 40% in patients with type 2 diabetes.
Agency officials said they would now consider warning doctors against prescribing Avandia in patients with cardiovascular disease, those taking nitrate drugs for angina, or those with congestive heart failure. Experts and officials said they also saw strong evidence that patients who have taken insulin for a long period of time should also avoid the drug.
"These are the people who I think clinicians are going to have to think twice before they prescribe this medicine," said Rosen, an osteoporosis and endocrinology expert at the Maine Center for Osteoporosis in Bangor.
A similar drug, Rezulin, was pulled off the U.S. market in March 2000 because of evidence it led to liver toxicity.
An article published in The New England Journal of Medicine in June rekindled the controversy over Avandia when researchers concluded it spurred a 43% rise in heart attack risk. Widespread reporting of the study caused many Avandia patients to fear that the drug may cause them more harm than good.
Experts said they were frustrated by a lack of reliable data clearly showing which patients are at risk and which may be able to safely use the drug.
Still, there appeared to be significant disagreement within the FDA's leadership about whether Avandia should remain on the market. Gerald Dal Pan, MD, the director of the agency's office of surveillance and epidemiology, announced that he agreed that Avandia should no longer be sold.
It is highly unusual for a senior FDA official to offer an opinion about a drug's future during expert deliberations. Dal Pan said his statement reflected "a personal recommendation," and not an official agency position.
But Robert Meyer, MD, director of the FDA's office of new drug evaluation, said there was "significant disagreement" among regulators over whether they had enough evidence to act against the drug.
Krall said in a later statement that GlaxoSmithKline was pleased with Monday's vote. "The committee recognized the debilitating nature of this disease ad the importance of multiple treatment option."
SOURCES: Clifford Rosen, senior staff scientist, Maine Center for Osteoporosis; acting chair, FDA advisory panel. Ronald Krall, MD, chief medical officer, GlaxoSmithKline. The New England Journal of Medicine, Number 24, June 14, 2007. David S. Schade, MD, professor of medicine, University of New Mexico School of Medicine; member, FDA panel. David Graham, MD, safety reviewer, FDA. Gerald Dal Pan, MD, director, FDA office of surveillance and epidemiology. Robert Meyer, MD, director, FDA office of new drugs.
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