The FDA is informing physicians and patients(www.fda.gov) about the increased risk of heart attack and stroke in patients with a history of cardiovascular disease who use the prescription weight-loss drug sibutramine hydrochloride.
The same day the FDA announced its most recent action regarding sibutramine, a European Medicines Agency committee went even further to curb use of the drug, recommending the suspension of marketing authorizations(www.ema.europa.eu) for all anti-obesity medications containing sibutramine.
According to the Committee for Medicinal Products for Human Use, doctors should no longer prescribe, and pharmacists should no longer dispense, products containing sibutramine.
Abbott Laboratories, which manufactures and distributes sibutramine under the brand names Ectiva, Raductil, Reductil and Sibutral in Europe, said in a Jan. 21 press release(www.presseportal.de) that despite its belief that "sibutramine has a positive benefit/risk profile when used appropriately in the approved patient population," the company would suspend its marketing of these products.
"We believe there are many patients who benefit from sibutramine and respectfully disagree with the committee's opinion and the recommendation to suspend the medicine," said Eugene Sun, M.D., Abbott's VP of global pharmaceutical research and development. "However, we will act promptly to comply with the committee's recommendation."
The marketing authorization for all medications containing sibutramine has been suspended in more than two dozen European countries, including France, Germany, Spain and the United Kingdom.
The drug label for sibutramine, which is marketed as Meridia in the United States, already includes warnings about its use in patients with cardiovascular disease. However, the FDA said on Jan. 21 that manufacturer Abbott Laboratories agreed to add a history of cardiovascular disease as a new contraindication to sibutramine's label following the agency's review of additional data(www.fda.gov) from an ongoing safety review launched in November.
The FDA said the contraindication will state that sibutramine should not be used in patients with a history of cardiovascular disease, including:
- coronary artery disease (myocardial infarction, angina);
- stroke or transient ischemic attack;
- heart arrhythmias;
- congestive heart failure;
- peripheral arterial disease; or
- uncontrolled hypertension.
The agency advised patients who are currently using sibutramine to talk with their physicians to determine if continued use of the drug is appropriate.
According to FDA officials, physicians should regularly monitor the blood pressure and heart rate of patients using sibutramine. If sustained increases in blood pressure and/or heart rate are observed, use of the drug should be discontinued.
The FDA also said the weight-loss medication should be discontinued in patients who do not lose at least 5 percent of their baseline weight within the first three to six months of treatment because continued use is unlikely to be effective and exposes patients to unnecessary risk.
In a study of 10,000 people, cardiovascular events occurred in 11.4 percent of patients using sibutramine compared with 10 percent of patients taking a placebo. The FDA said the difference was higher than expected and indicated that sibutramine was associated with an increased cardiovascular risk. Furthermore, the increased risk for cardiovascular events with sibutramine occurred only in patients with a history of cardiovascular disease.
After the FDA completes its review of additional safety data -- which is expected to be submitted to the FDA by Abbott in March 2010 -- and other relevant information related to sibutramine's potential benefits and risks, the agency will convene an open public advisory committee meeting to discuss the drug's benefit/risk profile and determine if additional regulatory actions should be taken.