Sibutramine hydrochloride monohydrate, a schedule IV controlled substance that is structurally related to amphetamine, has been approved by the U.S. Food and Drug Administration for the treatment of obesity. Medical Letter consultants reviewed current information about this new drug.

Sibutramine inhibits the reuptake of norepinephrine, serotonin and dopamine. Through this mechanism, concentrations of neurotransmitters are increased in the brain. The drug is rapidly absorbed from the gastrointestinal tract and is almost completely metabolized on its first pass through the liver. The active metabolites reach a peak concentration in serum in three to four hours, are primarily excreted in urine and partly in feces, and have a half-life of 14 to 16 hours. Results of an unpublished multicenter double-blind trial that placed 1,047 obese patients on a restricted-calorie diet demonstrated that patients taking placebo lost 0.9 kg. Patients taking 1-, 5-, 10-, 15-, 20- and 30-mg doses of sibutramine daily during the 24-week trial lost 1.8, 3.1, 4.4, 5.3, 5.8 and 6.5 kg, respectively. In other year-long unpublished studies, weight reduction reached a maximum by six months and was more or less maintained for another six months, with some regains by the end of one year.

The most common side effects of sibutramine were dry mouth, headache, insomnia and constipation. The drug caused dose-related increases in heart rate and blood pressure, some of which were clinically significant. No echocardiographic heart valve abnormalities were reported such as those that led to the removal of fenfluramine and dexfenfluramine from the market. Also, none of the patients developed pulmonary hypertension. Ketoconazole and erythromycin can increase serum concentrations of sibutramine, but the clinical significance of these elevations is unknown. Sibutramine should not be used with other serotonergic drugs including selective serotonin reuptake inhibitors, serotonin agonists for migraine, lithium, meperidine, fentanyl or dextromethorphan, or within two weeks of therapy with a monoamine oxidase inhibitor. The manufacturer states that the initial dosage of sibutramine, 10 mg daily, can be increased in four weeks to 15 mg daily if blood pressure and heart rate are stable. Sibutramine is available in 5-, 10- and 15-mg tablets; a 30-day supply of 15-mg tablets would cost a pharmacist about $113.

Medical Letter consultants advise against using sibutramine, although limited unpublished data indicate that it is modestly effective in reducing weight for six months. Dose-related increases in blood pressure and heart rate levels can occur, and long-term safety is unknown.