The popular new cholesterol-lowering drug Crestor may cause an increased risk of potentially life-threatening muscle damage, especially in people of Asian ancestry, the Food and Drug Administration said yesterday.
In a formal advisory, the agency said the risk is small and was largely identified and understood when the drug was approved in 2003. But because of new post-market studies that underscored the concerns, the agency concluded that the public should be informed and that warnings on the product label should be strengthened.
The advisory, and accompanying new instructions to physicians, reflect a recent policy shift in how and when the FDA releases potentially troublesome information about a product. In the wake of criticism that the agency did not move fast enough in communicating potential problems with COX-2 painkillers, including Merck's Vioxx, FDA officials said they plan to give out more preliminary information than in the past.
"Today's FDA advisory on Crestor is part of an ongoing effort to notify the public of potentially significant emerging safety data so that they can make more informed choices about their medical care," said Steven Galson, acting director of the FDA's Center for Drug Evaluation and Research.
The manufacturers of Crestor, AstraZeneca, said the label revisions proposed by the company, and approved by the FDA, "provide physicians with further clarification on how best to use Crestor with their patients." The company added: "We continue to believe Crestor is safe and effective when used according to the prescribing information."
Crestor, an especially powerful statin that can lower high cholesterol levels faster than many others, has been linked to some fatal cases of muscle damage known as rhabdomyolysis, which can lead to kidney failure. In its advisory, the FDA said clinical trials of Crestor and post-market studies had found that in rare cases it, like other statins, caused muscle damage.
The advisory was sharply criticized by Sidney Wolfe of Public Citizen's Health Research Group, a consumer advocacy organization. Wolfe's group petitioned the FDA in October to ban Crestor, and he called yesterday's FDA action "yet another example of the agency's dangerous cowardice in failing to adequately protect people in this country from uniquely dangerous prescription drugs."
Wolfe said that since the drug came on the market in September 2003, it has been linked to 117 cases of rhabdomyolysis and 41 cases of kidney failure -- which he said are higher totals than for other statins on the market. He also said that because of the safety concerns, several countries, including Germany, Norway and Spain, have not approved Crestor.
In their statements, the FDA and AstraZeneca said patients should no longer be started at what had been the highest approved dose of 40 milligrams, but at 20 milligrams. The FDA said that at higher doses, Crestor appeared to cause more bits of protein and blood in urine, a precursor to possible kidney trouble. In his statement, Wolfe said Crestor is the only statin for which higher doses are linked to a higher rate of these side effects.
The FDA also said that in a study of a broad range of Asians, Crestor levels in the blood were found to be twice as high as with white people given the same dosage.