Panel rejected over-the-counter indication for statin

Panel members said that patients may not appropriately self-select and that a health care professional should be involved in statin therapy.

A Food and Drug Administration advisory panel rejected an over-the-counter indication for lovastatin 20 mg due to concerns about consumer ability to use the drug properly without oversight by a health care provider.

The combined Nonprescription Drugs and Endocrinologic and Metabolic Drugs Advisory committees decided in a 20-3 vote not to recommend to the FDA the over-the-counter indication. The FDA regularly convenes expert panels prior to making regulatory decisions and typically follows the recommendation of the panel.

“I am convinced that Mevacor [lovastatin, Merck] is safe and effective for the target population proposed, but it’s a moving target. I don’t think patients can appropriately self-select, and it is important that a health care professional remain involved,” said Nelson Watts, MD, who voted against the requested indication. Watts is professor of medicine at the University of Cincinnati.

Panel chairman Alastair Wood, MD, professor of medicine and pharmacology at Vanderbilt University School of Medicine, voted yes and called the argument about inappropriate self-selection “paternalistic.”

Alastair Wood

“There are clearly people who will derive substantial benefit from this therapy, and one of the attractions of over-the-counter availability is that patients have the ability to make that decision,” Wood said. “I’m uncomfortable saying we’re not going to approve a drug for over-the-counter use because some people might take the drug and not get benefit.”

Safe and effective

Speaking on behalf of Merck, Jerome Cohen, MD, director of preventive cardiology at St. Louis University, reminded panel members that lovastatin had been available for 17 years with 27 million patient years of experience. “The risk of having a serious event with low-dose aspirin is greater than it is with lovastatin 20 mg,” Cohen said.

During the official vote, panel members agreed that 20 mg of lovastatin is effective at lowering LDL cholesterol. They unanimously agreed that concerns about muscle toxicity and liver function would not be enough to prevent the agent from moving to over-the-counter status.

Five panel members said concerns about risks in women with childbearing potential would prevent an over-the-counter indication, but Merck representatives argued that prescription lovastatin is already contraindicated for pregnant women.

To move lovastatin to over-the-counter status, Merck had to provide data that would simulate the over-the-counter experience. Representatives presented CUSTOM (Consumer Use Study of OTC Mevacor), which enrolled 3,316 patients. It concluded that 90% showed correct behavior according to safety criteria and that 55% complied with all label requirements.

Jerry Hansen, RPh, vice president of new product development and consumer research at Merck and Johnson & Johnson, said these patients were highly motivated to protect their health but were unlikely to take a prescription product.

“This group is three times more likely to consider taking an over-the-counter product than using a prescription,” Hansen said. “They believe a cholesterol-lowering prescription product is for someone who is sick, whereas an over-the-counter product is for someone who is healthy like themselves.”

The panel argued that only 337 of the 3,316 participants who traveled to mock-pharmacy study sites met the study criteria: LDL cholesterol >130 mg/dL with two other cardiovascular risk factors.

“I think CUSTOM was a failed study,” said Paul Woolf, MD, chairman of the department of medicine at Crozer Chester Medical Center in Upland, Pa. “The way it was set up, only 10% of the population met the criteria and some of them didn’t have high cholesterol to begin with.”

OTC experience

During the two-day meeting, the over-the-counter experience with simvastatin (Zocor, Merck) in the United Kingdom was a frequent topic of discussion. Michael Koenig, PhD, of the FDA Administration Division of Over-the-Counter Drug Products, said the regulatory bodies in the United Kingdom considered many of the same issues the advisory panel was being asked to consider.

The United Kingdom decided to classify simvastatin as a “pharmacy” product, which is a third category not present in U.S. pharmaceutical law, where medications are placed behind-the-counter and distributed with a pharmacist consultation. Koenig said simvastatin was not in the “general sales list” category, which would be equivalent to over-the-counter status in the United States.

Simvastatin has been in the pharmacy category for six months. A representative from Merck said that it is too early “to judge exactly how well this is working, although we’re committed to making sure it works.”

Several panel members said that if they had the option of pharmacist control, they would have voted to recommend the over-the-counter indication. “A behind-the-counter option would be the perfect solution to this dilemma. Mevacor seems to be useful for heart health, but because of the nature of health marketing, it shifts the risk/benefit ratio too far toward risk,” said Leslie Clapp, MD, a pediatrician at Main Street Pediatrics in Buffalo, N.Y. – by Jeremy Moore

Dr. Watts is a paid consultant for Merck.