First weight loss Rx in 20 years clears the FDA
Redux (dexfenfluramine, Interneuron Pharmaceuticals), a serotonergic appetite suppressant, has received Food & Drug Administration approval for the management of obesity in patients on a reduced-calorie diet. It is approved for both initial weight loss and maintenance of weight loss, so pharmacists can expect to see it used long-term. The first appetite suppressant to clear the FDA in 20 years, dexfenfluramine has been available in Europe for more than a decade and has been used by an estimated 10 million patients.
Dexfenfluramine appears to increase serotonin levels by three different mechanisms. Robert Kushner, M.D., director of the Nutrition and Weight Control Clinic at the University of Chicago, explained that, like the selective serotonin reuptake inhibitors, dexfenfluramine also inhibits the reuptake of serotonin. In addition, it releases serotonin into the synaptic cleft and decreases presynaptic uptake. "So, it not only releases it, but it reduces uptake into the presynaptic and postsynaptic neuron," he said. Increased serotonin levels are associated with decreased caloric intake.
In a one-year clinical trial of 900 obese patients, those who dieted and took dexfenfluramine lost significantly more weight than patients who dieted and took placebo. At the end of one year, 64% of the patients maintained on dexfenfluramine lost at least 5% of their initial weight, 40% lost at least 10%, and 21% lost at least 15%.
Dexfenfluramine was also shown to be beneficial in a study of 60 obese patients who had already lost an average of 10 pounds on diet alone. The addition of dexfenfluramine resulted in a further 26% reduction of initial excess weight.
In the clinical trials, the most common adverse events were diarrhea (17.5%), dry mouth (12.5%), and somnolence (7.1%). The side effects were mild and abated with continued use.
Dexfenfluramine has been classified as a Schedule IV controlled substance, but the drug will probably be "descheduled" later this year. Dexfenfluramine is contraindicated for use in patients with pulmonary hypertension. In patients using anorexiants, primary pulmonary hypertension has been shown to occur at the rate of 18 cases per one million users per year, up from two to three cases per year per one million people in the general population.
Questions about the potential for dexfenfluramine to cause neurotoxicity recently prompted some neuroscientists to request the FDA to delay approving the drug. Their request was based on a study showing that rats given high doses of dexfenfluramine experienced neurochemical changes in the brain. This safety concern is addressed in the product's labeling, which points out that the doses used in the rodent study were much higher than the doses recommended for humans. …