Diet drug gets FDAs nod but must undergo cardiac trial

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The FDA approved the weight-management drug Qsymia, a combination of the two FDA-approved drugs phentermine and topiramate, in an extended-release formulation. The agency also is requiring a long-term outcomes trial to assess the drug’s cardiovascular effects.  

The drug was approved July 17 for use in adults with a body mass index (BMI) of 30 or greater (obese) or adults with a BMI of 27 or greater (overweight) who have at least one weight-related condition such as hypertension, type 2 diabetes or dyslipidemia. The FDA recommends that the use of Qsymia should complement a healthy lifestyle that includes a reduced-calorie diet and exercise.

Phentermine is indicated for short-term weight loss in overweight or obese adults who are exercising and eating a reduced calorie diet. Topiramate is indicated to treat certain types of seizures in people who have epilepsy and to prevent migraine headaches.

Qsymia can increase heart rate, and the drug’s effect on heart rate in patients at high risk for heart attack or stroke is not known. Therefore, the use of Qsymia in patients with recent (within the last six months) or unstable heart disease or stroke is not recommended. Regular monitoring of heart rate is recommended for all patients taking Qsymia, especially when starting Qsymia or increasing the dose.

Additionally, Qsymia must not be used during pregnancy because it can cause harm to a fetus, or by patients with glaucoma or hyperthyroidism.

“We welcome a new tool, in addition to healthy diet and exercise, to help patients combat obesity. However, it is important to continuously evaluate the overall risks and benefits of any weight-loss aid,” said American College of Cardiology President William Zoghbi, MD, in a statement. “Weight-loss drugs have the potential to help manage obesity, which is a major health problem, but it is most important to understand the impact the medications may have on long-term cardiovascular health and patient outcome.”

The FDA nixed the combination drug in 2010, calling for more data on cardiovascular events and the drug’s effect on pregnant women. Drug developer Vivus agreed to conduct an analysis of existing data. In February, the FDA’s advisory panel voted 20 to two in favor of approval based on its benefit-risk profile.

The recommended daily dose of Qsymia contains 7.5 mg of phentermine and 46 mg of topiramate extended-release. Qsymia is also available at a higher dose (15 mg phentermine and 92 mg of topiramate extended-release) for select patients.

Qsymia is marketed by Vivus, based in Mountain View, Calif. The FDA wants Vivus to conduct 10 postmarketing requirements, including a long-term cardiovascular outcomes trial to assess the effect of Qsymia on the risk for major adverse cardiac events such as heart attack and stroke.

The safety and efficacy of Qsymia were evaluated in two randomized, placebo-controlled trials that included approximately 3,700 obese and overweight patients with and without significant weight-related conditions treated for one year. All patients received lifestyle modification that consisted of a reduced calorie diet and regular physical activity.

Results from the two trials showed that after one year of treatment with the recommended and highest daily dose of Qsymia, patients had an average weight loss of 6.7 percent and 8.9 percent, respectively, over treatment with placebo. Approximately 62 percent and 69 percent of patients lost at least 5 percent of their body weight with the recommended dose and highest dose of Qsymia, respectively, compared with about 20 percent of patients treated with placebo.

Patients who did not lose at least 3 percent of their body weight by week 12 of treatment with Qsymia were unlikely to achieve and sustain weight loss with continued treatment at this dose. Response to therapy with the recommended daily dose of Qsymia should be evaluated by 12 weeks to determine, based on the amount of weight loss, whether to discontinue Qsymia or increase to the higher dose.

If after 12 weeks on the higher dose of Qsymia, a patient does not lose at least 5 percent of body weight, then Qsymia should be discontinued, as these patients are unlikely to achieve clinically meaningful weight loss with continued treatment.