The Food and Drug Administration urged doctors Wednesday to use caution in prescribing the cholesterol drug Crestor to patients of Asian heritage, but said that overall the medication carried no higher risk of serious side effects than its competitors.
Issuing a public health advisory and changes to prescribing information for doctors, the agency said that Asian patients should be started at the lowest approved dose, 5 milligrams a day.
Because Asians appear to process the drug differently, half the standard dose can have the same cholesterol-lowering benefit in those patients, though a full dose could increase the risk of side effects, a study by the drug's manufacturer, AstraZeneca, indicated.
The FDA also strengthened a warning for patients in the general population that high doses of the drug -- 40 milligrams daily -- could increase risks of life-threatening muscle damage.
But it rejected assertions by an FDA whistle-blower, Dr. David J. Graham, and by consumer advocates that Crestor was a dangerous drug and should not be marketed in the U.S.
The agency said Crestor posed no greater risk of severe muscle damage or kidney failure than other drugs in its class of cholesterol-reducing statins, which includes Lipitor and Zocor. Statins work by blocking the body's production of cholesterol.
More than 4 million patients have taken Crestor since it was approved in August 2003, but analysts have lately scaled back their estimates of its future prospects, citing safety concerns. Global sales of the heavily advertised drug reached $908 million last year. In the U.S., a month's supply typically costs about $89, according to the seniors' organization AARP.
The FDA action may ease worries among some doctors and patients, said Dr. Benjamin Ansell, a cholesterol expert at UCLA. Crestor was flagged by Graham as one of five dangerous drugs on the market in Senate testimony last fall.
"The FDA has been under fire, and it is taking a more proactive approach by being very specific with its language," Ansell said, pointing to the focus on Asian patients as an example.
Clinical trials in Asian countries previously showed that patients reacted differently to Crestor than patients in U.S. trials, most of whom were white. But the medical community was uncertain if these differences also applied to Asians in the U.S. So the FDA requested more studies by the manufacturer, which led to the finding.
"As someone who takes care of a lot of patients who are Asian Americans, I didn't know whether to assume they were 'Asian' or 'American,' " Ansell said. "This gives us a guide to the good practices we should be using."
The FDA said it was unclear why people of Asian heritage reacted differently to Crestor.
"We wanted to make sure it was not some environmental effect of living in Asia, such as diet, as opposed to genetics," said an agency spokeswoman who spoke on condition of anonymity.
"I don't believe the FDA has ever issued anything specific to Asian patients before," she added.
A leading critic of the drug said the FDA's claim that the drug had a similar safety profile to its competitors was misleading and showed "dangerous cowardice."
"These changes are so minimal and misleading that they can hardly be viewed as anything but what the company was willing to accept," said Dr. Sidney Wolfe of the advocacy group Public Citizen, which has petitioned the FDA to withdraw Crestor.
Wolfe said the agency was ignoring reports of muscle damage and kidney failure. The FDA said it was preparing a full response to Public Citizen's petition.
"The FDA stands by our analysis of the risks and benefits of Crestor," said the agency spokeswoman.
AstraZeneca, a British-Swedish pharmaceutical company with U.S. headquarters in Wilmington, Del., said it was pleased with the FDA's action. Spokeswoman Kellie Caldwell said the company had suggested making changes to the prescribing information for doctors.
"They were initially submitted by AstraZeneca," she said. "We initiated the process."