Physicians should stop prescribing sibutramine and contact patients who are taking the weight-loss drug -- which is marketed as Meridia -- following the FDA's recent decision to ask the drug's manufacturer to remove the product from the market(www.fda.gov).
John Jenkins, M.D., director of the Office of New Drugs in the FDA's Center for Drug Evaluation and Research, said during an Oct. 8 news conference that there were known risks (i.e., increased blood pressure and heart rate) associated with sibutramine when the agency approved the drug in 1997 for weight loss and maintenance of weight loss in obese patients. At the time, Jenkins said, the FDA thought the potential cardiovascular benefits obese patients could achieve through weight loss outweighed those risks.
However, the FDA asked manufacturer Abbott Laboratories(www.fda.gov) to voluntarily withdraw the product from the market after the agency completed its review of findings from the Sibutramine Cardiovascular Outcomes, or SCOUT, trial, which concluded last year.
"The data for this trial showed that patients treated with sibutramine did not experience the expected cardiovascular benefit from losing weight," Jenkins said. "Instead they experienced a 16 percent higher rate of cardiovascular events, such as heart attack and stroke, compared to patients who took placebo."
Patients who took sibutramine during the five-year SCOUT trial lost an average of only 2.5 percent more weight than did patients taking placebo, Jenkins said.
In addition to its recommendation to stop prescribing the drug, the FDA issued the following recommendations for physicians:
- contact patients taking sibutramine and ask them to stop taking it;
- be aware of the possible risk of cardiovascular events among patients taking sibutramine and assess patients for such events if they present with signs or symptoms of cardiovascular disease;
- inform patients of the risks associated with the medication;
- discuss alternative weight-loss strategies with patients; and
- report side effects to the FDA's MedWatch program(www.accessdata.fda.gov).
Jenkins said sibutramine can increase heart rate and blood pressure while a patient is taking the drug, but FDA officials are unaware of any long-term problems among patients after they stop taking the medication.
Gerald Dal Pan, M.D., M.H.S., director of the Office of Surveillance and Epidemiology at the FDA's Center for Drug Evaluation and Research, said during the news conference that when confronted with a significant safety issue, the agency typically considers whether there is a patient population that still might benefit from a medication despite its risks. He said the FDA considered -- but ultimately decided against -- pursuing potential Risk Evaluation and Mitigation Strategies that would have made sibutramine available to select groups of patients.
"In the case of Meridia," said Dal Pan, "the weight loss achieved by patients was so modest that FDA could not find a single group of patients for whom the benefits of the drug outweighed the risk of heart attack or stroke."
An FDA advisory panel met Sept. 15 to review data from the SCOUT trial. Members of the Endocrinologic and Metabolic Drugs Advisory Committee were asked whether the agency should allow continued marketing of sibutramine without labeling changes. Other options presented were to allow continued marketing with a revised label, including a black box warning; continued marketing with revised labeling and restricted distribution; and withdrawal from the market.
Half of the 16-member panel voted to remove the product from the market, while six voted for continued marketing with a revised label and restricted distribution. Two voted for continued marketing with labeling changes.
According to published reports, the same advisory panel voted in September to not recommend approval of lorcaserin, a new weight-loss drug manufactured by Arena Pharmaceuticals, because of safety concerns. Panel members also voted in July against recommending approval of Qnexa, a weight-loss drug produced by Vivus Inc. that combines phentermine and topiramate.
A third weight-loss drug, Orexigen Therapeutics Inc.'s Contrave, is expected to be reviewed by the FDA panel this year. That product contains naltrexone and bupropion.
Despite the withdrawal of sibutramine and the rejection of two other weight-loss products by its advisory committee, Jenkins said the FDA supports the development of safe and effective weight-loss products because of the serious health problems associated with obesity.
Dal Pan said the withdrawal of sibutramine will affect about 100,000 U.S. patients.
Mary Parks, M.D., director of the FDA's Division of Metabolic and Endocrine Drug Products, said that to be approved by the agency, new weight-loss drugs must perform "significantly better than placebo" during clinical trials or help patients lose at least 5 percent of their body weight.
Parks acknowledged that the withdrawal of sibutramine leaves patients with limited options in terms of FDA-approved drugs for weight loss. Orlistat -- which is marketed as Xenical in prescription strength and as the lower-dose OTC product Alli -- is the only remaining product on the market that can be used long term for weight loss.
Phentermine and diethylpropion are not approved for long-term use.
"FDA is strongly encouraging patients to discuss with their health care providers the most appropriate options for them, including lifestyle and nonpharmacological interventions," Parks said.