FDA approves once-daily phentermine and topiramate extended-release for weight management

July 20, 2012

FDA has approved once-daily phentermine and topiramate extended-release (Qsymia, Vivus) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index of 30 or greater, or 27 or greater in the presence of at least 1 weight-related comorbidity.

FDA has approved once-daily phentermine and topiramate extended-release (Qsymia, Vivus) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 or greater (obese), or 27 or greater (overweight) in the presence of at least 1 weight-related comorbidity, such as hypertension, type 2 diabetes mellitus or high cholesterol (dyslipidemia).

Last month, Formularyreported that FDA approved lorcaserin (Belviq, Arena Pharmaceuticals and Eisai) as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients with an initial body mass index (BMI) of 30 kg/m2 or greater (obese), or 27 kg/m2 or greater (overweight) in the presence of at least 1 weight-related comorbid condition (eg, hypertension, dyslipidemia, type 2 diabetes).

The combination of phentermine and topiramate for weight loss is quite interesting, according to Formulary advisor James M. Wooten, PharmD, associate professor, department of medicine, section of clinical pharmacology, University of Missouri-Kansas City. “The anorectic effect of phentermine is probably a result of its action on the hypothalamus where it stimulates the release of norepinephrine,” Dr Wooten said. “The weight loss mechanism of action of topiramate, an anticonvulsant used to treat seizures, migraine headaches, etc., is less clear but it may be due to topiramate’s ability to reduce gastrointestinal motility which results in reduced satiety.

“Studies have shown a weight reduction of 10% to 15% in 56 weeks in obese patients. It may also have positive effects on type 2 diabetes as well as dyslipidemia.  Clinical studies have demonstrated a positive safety profile for this combination drug, which may be due to the relatively low dosages of each of its constituents,” Dr Wooten continued. “That being said, efficacy and safety must be demonstrated over a longer period of time in various patient types before this agent can be recommended as a first-line weight loss drug.”

"Qsymia is the first FDA-approved once daily combination treatment for patients struggling with obesity," Peter Tam, president of Vivus, said in a press release. "The degree and severity of obesity and the lack of effective pharmacological interventions that we face as a society were two primary reasons for the development of Qsymia. We are pleased with FDA's decision today because patients and physicians now have another treatment option available to them. It is expected that Qsymia will be available in the fourth quarter of 2012."

The safety and efficacy of phentermine and topiramate extended-release were evaluated in 2 multicenter, phase 3 trials that included severely obese patients (the EQUIP study), and overweight or obese patients with at least 2 weight-related comorbidities, such as hypertension, hypertriglyceridemia, type 2 diabetes, or central adiposity (the CONQUER study).  The average weight loss in EQUIP was 10.9% on phentermine and topiramate extended-release 15 mg/92 mg and 1.6% for placebo (ITT-LOCF, P<.0001). The average weight loss in CONQUER was 9.8% on phentermine and topiramate extended-release 15 mg/92 mg, 7.8% on phentermine and topiramate extended-release 7.5 mg/46 mg and 1.2% for placebo (ITT-LOCF, P<.0001).

The most common adverse reactions for patients treated with phentermine and topiramate extended-release included tingling sensation of hands and feet, dizziness, altered taste, insomnia, constipation, and dry mouth.

Phentermine and topiramate extended-release was approved with a Risk Evaluation and Mitigation Strategy (REMS) with a goal of informing prescribers and female patients of reproductive potential about an increased risk of orofacial clefts in infants exposed to phentermine and topiramate extended-release during the first trimester of pregnancy, the importance of pregnancy prevention for females of reproductive potential receiving phentermine and topiramate extended-release and the need to discontinue phentermine and topiramate extended-release immediately if pregnancy occurs.  The phentermine and topiramate extended-release REMS program includes a Medication Guide, Healthcare Provider training, distribution through certified pharmacies, implementation system and a timetable for assessments. 

As part of the approval of phentermine and topiramate extended-release, Vivus is committed to conduct post-marketing studies. The company will conduct a study to assess the long-term treatment effect of phentermine and topiramate extended-release on the incidence of major adverse cardiovascular events in overweight and obese subjects with confirmed cardiovascular disease, studies to assess the safety and efficacy of phentermine and topiramate extended-release for weight management in obese pediatric and adolescent subjects, studies to assess drug utilization and pregnancy exposure, a study to assess renal function, as well as animal and in vitro studies.