Sibutramine Contraindicated in Cardiovascular Patients

According to an alert posted by MedWatch, the FDA's safety information and adverse event reporting program, the announcement is a follow-up to an ongoing safety review of preliminary results reported in November 2009, which first raised concerns about this issue.

According to the FDA, the drug label already warns against the use of sibutramine in patients with cardiovascular disease. "However, based on the serious nature of the review findings, FDA requested and the manufacturer agreed to add a new contraindication to the sibutramine drug label," stating that sibutramine should not be used in patients with a history of cardiovascular disease, including patients with a:

• History of coronary artery disease (eg, myocardial infarction, angina)
• History of stroke or transient ischemic attack
• History of heart arrhythmias
• History of congestive heart failure
• History of peripheral arterial disease
• Uncontrolled hypertension (eg, >145/90 mm Hg)

The safety review was based on data from the Sibutramine Cardiovascular Outcomes Trial (SCOUT), which enrolled more than 10,000 overweight or obese patients with diabetes or a history of coronary artery disease, peripheral vascular disease, or stroke, along with other cardiovascular risk factors.

An analysis of the trial's primary end point -- a composite of myocardial infarction, stroke, resuscitated cardiac arrest, or death -- found the rate to be 11.4% for patients receiving sibutramine and 10% for those receiving placebo. The current review found that the risk for cardiovascular events with sibutramine was significantly increased only in patients with a history of cardiovascular disease (P = .023).

Healthcare professionals should regularly monitor blood pressure and heart rate in patients taking sibutramine, the FDA notes.

"If sustained increases in blood pressure and/or heart rate are observed, sibutramine should be discontinued," according to the FDA. "Additionally, sibutramine should be discontinued in patients who do not lose at least 5% of their baseline body weight within the first 3 to 6 months of treatment, as continued treatment is unlikely to be effective and exposes the patient to unnecessary risk."

The full study report for SCOUT is expected in March 2010, at which time an open public advisory committee meeting will be convened to determine whether additional regulatory actions should be taken to ensure the safe use of sibutramine.

Meanwhile, the European Medicines Agency (EMEA) also announced the results of its safety review of drugs containing sibutramine, citing the SCOUT data. According to a press release, the EMEA concluded, "The risks of these medicines are greater than their benefits."

The EMEA statement goes on to say that physicians should no longer prescribe sibutramine-containing agents, pharmacists should no longer dispense them, and patients taking them should make an appointment to see their physicians "at the next convenient time."

More information is available on the FDA's MedWatch Web site and on the EMEA Web site.