The combination of phentermine and topiramate has been approved for the treatment of weight loss with stipulations: a risk evaluation and mitigation strategy that addresses the potential teratogenic and adverse cardiac effects of the product, according to the Food and Drug Administration.
In the widely anticipated FDA announcement on July 17, Dr. Janet Woodcock, director of the agency’s Center for Drug Evaluation and Research, said in a statement that the phentermine-topiramate combination "used responsibly in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, provides another treatment option for chronic weight management in Americans who are obese or are overweight and have at least one weight-related comorbid condition."
The combination has been approved for treatment of adults with a body mass index of at least 30 kg/m2, or those with a BMI of at least 27 who also have weight-related comorbidities.
The product contains an immediate-release formulation of phentermine, a sympathomimetic amine approved for short-term weight loss that has been marketed in the United States since 1959; and a controlled-release formulation of topiramate, approved for treating adult epilepsy in 1996, migraine prophylaxis in 2004, and pediatric epilepsy in 2011.
The combination has been approved for treatment of adults with a body mass index of at least 30 kg/m2, or those with a BMI of at least 27 who also have weight-related comorbidities, in combination with diet and exercise.
The risk evaluation and mitigation strategy (REMS) addresses the teratogenicity of topiramate, which is known to increase the risk of oral clefts at the higher doses used for treating epilepsy, and the possible adverse cardiac effects of phentermine, which increases the pulse rate. The REMS includes a patient medication guide that is provided with each filled prescription, health care provider training, and distribution of the product through certified pharmacies.
It will be marketed as Qsymia by Vivus, not Qnexa, the original proposed trade name. After a starting dose of 3.75 mg/23 mg of phentermine/topiramate daily for 2 weeks, the recommended dose is 7.5 mg of phentermine with 46 mg of extended-release topiramate. A higher dose (15 mg/92 mg) is available for select patients who do not reach their weight-loss goal. These phentermine and topiramate doses are lower than the doses available for the two products available separately.
"Females of reproductive potential must not be pregnant when starting Qsymia therapy or become pregnant while taking Qsymia," should have a negative pregnancy test before starting treatment and monthly during treatment, and should consistently use effective contraception while on the weight-loss drug, according to the FDA statement. If a patient on treatment does not lose at least 5% of body weight after 12 weeks on the higher dose, treatment should be stopped, "as these patients are unlikely to achieve clinically meaningful weight loss with continued treatment," the statement added.
Approval was based on the results of two, 1-year studies involving nearly 4,000 obese and overweight people, mostly white females, with and without significant comorbidities, comparing phentermine-topiramate to placebo. Patients on the recommended and the higher doses of phentermine-topiramate lost an average of 6.7% and 8.9% of their weight, respectively, over those on placebo. About 62% of those on the recommended dose and 69% of those on the highest dose lost at least 5% of their baseline body weight, compared with about 20% of those on placebo. The most common side effects associated with treatment are paresthesias, dizziness, altered taste sensation, insomnia, constipation, and dry mouth.