Staff researchers at the Food and Drug Administration raised questions Wednesday about how well consumers understand guidelines for Mevacor, a cholesterol fighter that
wants to convert from prescription to over-the-counter status.
The FDA staff report didn't make a formal recommendation, but it focused on how well consumers would understand the benefits and possible risks of an over-the-counter product and understand the drug's label. As is common practice, FDA staffers posed questions and observations for FDA advisory panel members who will meet Thursday and Friday to discuss whether Mevacor is considered safe as an over-the-counter (OTC) product.
The FDA isn't required to follow recommendations by advisory panels, but it usually agrees. If Merck prevails, Mevacor would be the first OTC cholesterol drug in the U.S. A nonprescription version of Merck's Zocor has been available in the U.K. since July.
Four years ago, advisory panels rejected a similar request by Merck to take Mevacor over the counter. The FDA agreed, saying the company hadn't proved that the benefits outweighed the risks and hadn't demonstrated that consumers could take the drug safely without a doctor's prescription and supervision.
At the time, Merck was seeking OTC approval for a 10-milligram pill. This time, it is asking the FDA to approve a 20-milligram pill that would be aimed at people who are at risk of having a cardiovascular problem in the next 10 years.
Given the potential side effects, the FDA staff report asked whether Merck "provided adequate justification" for not requiring liver-function test-monitoring in an over-the-counter setting. It also wondered whether the potential liver-damage risk of nonprescription Mevacor in individuals with liver disease had been adequately addressed.
The staff report said cholesterol drugs known as statins -- Mevacor belongs to this group -- can raise certain liver enzymes, a signal for possible liver damage. However, the staff's research of medical databases shows that "these increases rarely result in serious liver injury; and in the few reports of liver injury, attribution to statin use cannot be established."
The report also noted that statins can cause muscle toxicity. The staff asked advisory panel members to beware of Mevacor interactions with other drugs that might increase the risk of this side effect. "Is the risk of muscle toxicity ... acceptable for an OTC drug?" the report said.
However, the report said a review of medical databases shows that such severe muscle damage is "a very rare event" and that the risk of this dangerous side effect "does not appear to outweigh the benefit" of Mevacor therapy.
The FDA staff raised more pointed questions about data from Merck on how well people understand a nonprescription label for Mevacor and how well they recognize if they are appropriate candidates for statin therapy.
"Ninety-nine percent of all the respondents who reported that they could start Mevacor OTC right away, self-selected incorrectly," the FDA staff report said. The patients guessed wrong because they didn't meet the eligibility criteria or because they had a medical condition that would make them unfit for a statin.
Other weaknesses in patients' comprehension included knowing when to consult a doctor for certain medical conditions, determining the proper health criteria for OTC statin use, and recognizing that cholesterol levels will go up if patients stop taking the drug.
"Does the frequency of appropriate self-diagnosis and self-selection support the conclusion that
Mevacor can be used safely and effectively in the OTC setting?" the report said.
also is seeking FDA approval to convert its prescription Pravachol to OTC status. Pravachol isn't being reviewed this week. Four years ago, FDA advisory committees rejected a similar request by Bristol-Myers Squibb.
Supporters of converting statins into nonprescription medications say such a switch is justified by the drugs' safety records and the fact that low doses of the drugs could help people with a moderate risk of heart disease as long as they also tried to reduce cholesterol via exercise and dieting.
Critics say that prescription statins even at the lowest doses necessitate periodic blood-test monitoring for rare but potentially dangerous liver and muscle side effects. They question whether low doses of nonprescription statins can be effective, they worry that patients might overmedicate themselves and they are concerned patients won't be as wary about interactions with other medications as they would if the statin were a prescription product.
Analysts who follow the Rx-to-OTC trends say drug companies usually seek to switch drugs to OTC status as
the products approach patent expiration, thus maintaining the drug's brand-name identity while softening the blow of generic competition.