Nonprescription Sales of Cholesterol Drug Rejected

FDA Panel Says Risk of Side Effects Outweighs Benefits

Federal advisers yesterday rejected a proposal to allow the sale of a powerful cholesterol-lowering pill without a prescription, saying the risk of side effects outweighed the possible benefits of preventing more heart attacks and strokes.

At the conclusion of an unusual joint meeting of two Food and Drug Administration expert committees, the panel voted 20 to 3 that the agency should deny a request from Merck & Co. and Johnson & Johnson to market a low-dose version of Merck's drug Mevacor to consumers without a doctor's order.

Although many members said they endorsed the general idea of increasing the use of cholesterol drugs called statins by making them more easily available, they said the proposal failed to do enough to ensure that only the right patients take the drug and are then closely monitored. Specifically, the advisers were concerned that pregnant women might take the drug, resulting in birth defects, and that patients might suffer rare but potentially life-threatening liver and muscle complications.

"I think that it is the right thing to do, but I don't think we're there yet," said panel member Frank F. Davidoff, editor emeritus of the Annals of Internal Medicine. "I think you could argue that going [over the counter with] statins would in effect be a massive uncontrolled experiment."

Several panel members said they would have preferred a plan that allowed the drug to be sold without a prescription, but only after consulting a pharmacist. A similar scheme was recently approved in Britain for a cholesterol drug.

The FDA will make the final decision on the Mevacor proposal, but the agency usually follows the advice of its advisers. The FDA rejected a similar request from Merck four years ago.

Merck officials, who had argued the move would prevent thousands of heart attacks each year, said they were disappointed by the decision but had not abandoned the idea.

"We continue to believe in the benefits of Mevacor . . . as an over-the-counter medication to help lower cholesterol and contribute to improved overall health," Merck spokesman Tony Plohoros said. "We will continue to work with the FDA toward that end."

The move would have marked a major shift in how the nation combats heart disease -- the leading cause of death in the United States -- by allowing millions of Americans much easier access to a drug that sharply reduces one of the leading risks. Had the proposal won approval, other companies were expected to follow, including Bristol-Myers Squibb Co., which has said it wants to sell an over-the-counter form of its statin, Pravachol.

The proposal came at a time when the FDA has come under intense criticism for being too lax about safeguarding the public from drug risks. In September, Merck took its blockbuster painkiller Vioxx off the market after discovering it increased the risk of heart attacks, and similar concerns have arisen over other drugs in the same class. Safety questions have also been raised about other statins, including Baycol, which was taken off the market, and Crestor.

Although the FDA has allowed drugs to switch from prescription to over-the-counter status in the past, it has always been for acute illnesses such as colds, aches and pains and heartburn. The Mevacor change would have marked the first time approval had been granted for nonprescription sale of a medication that would be taken for years to prevent a disease.

Research has clearly established that statins can sharply reduce the risk of heart attacks and strokes, primarily by lowering levels of "bad," or LDL, cholesterol. Although the drugs can produce life-threatening liver and muscle problems, they are generally considered safe, and only a small fraction of the number of people who would benefit are taking them.

The companies proposed allowing the sale of a 20-milligram pill targeted at an estimated 20 million to 30 million Americans who face a moderately elevated risk of a heart attack because their LDL levels are between 130 and 170 and they have at least one other risk factor, such as being a smoker or having high blood pressure.

During the hearing, Merck officials presented research that, they said, showed consumers would use the drug properly. They argued that the drug would be sold with strong warnings advising pregnant women not to take it, along with detailed instructions to get cholesterol tests before and while taking the pills and to be on the lookout for possible side effects.

But FDA officials said the company's own research showed that consumers frequently misunderstood who should take the drug, indicating that many people who should not be using the medication would take it, putting at risk people who would not necessarily benefit. That concern was echoed by consumer groups and several panel members, especially if the drug were to be heavily advertised.

Panel members also expressed concern that those who need the drug might not take high enough doses without a doctor's supervision, and that many people might take the drug instead of doing other beneficial things -- such as eating better and exercising more.