The FDA has approved Contrave (naltrexone hydrochloride and bupropion hydrochloride extended-release tablets) as treatment option for chronic weight management in addition to a reduced-calorie diet and physical activity.

The drug is approved for use in adults with a body mass index (BMI) of 30 or greater (obesity) or adults with a BMI of 27 or greater (overweight) who have at least one weight-related condition such as high blood pressure (hypertension), type 2 diabetes or high cholesterol (dyslipidemia).

BMI, which measures body fat based on an individual’s weight and height, is used to define the obesity and overweight categories. According to the Centers for Disease Control and Prevention, more than one-third of adults in the U.S. are obese.

“Obesity continues to be a major public health concern,” said Jean-Marc Guettier, M.D., director of the division of Metabolism and Endocrinology Products in FDA’s Center for Drug Evaluation and Research. “When used as directed in combination with a healthy lifestyle that includes a reduced-calorie diet and exercise, Contrave provides another treatment option for chronic weight management for people who are obese or are overweight and have at least one weight-related health condition.”

Contrave is a combination of two FDA-approved drugs, naltrexone and bupropion, in an extended-release formulation. Naltrexone is approved to treat alcohol and opioid dependence.  Bupropion is approved to treat depression and seasonal affective disorder and as an aid to smoking cessation treatment. 

The effectiveness of Contrave was evaluated in multiple clinical trials that included approximately 4,500 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 a clinical trial that enrolled patients without diabetes showed that patients had an average weight loss of 4.1% over treatment with placebo (inactive pill) at one year. In this trial, 42% of patients treated with Contrave lost at least 5% of their body weight compared with 17% of patients treated with placebo. Results from another clinical trial that enrolled patients with type 2 diabetes showed that patients had an average weight loss of 2percent over treatment with placebo at one year. In this trial, 36% of patients treated with Contrave lost at least 5% of their body weight compared with 18% of patients treated with placebo.

Patients using Contrave at the maintenance dose should be evaluated after 12 weeks to determine if the treatment is working. If a patient has not lost at least 5% of baseline body weight, Contrave should be discontinued, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.

The most common adverse reactions reported with Contrave include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea.

The FDA is requiring the following post-marketing requirements:

• a cardiovascular outcomes trial to assess the cardiovascular risk associated with Contrave use
• two efficacy, safety, and clinical pharmacology studies in pediatric patients (one in patients 12 to 17 years of age, and one in patients 7 to 11 years of age)
• a nonclinical juvenile toxicity study with a particular focus on growth and development as well as behavior, learning, and memory
• a study to evaluate the effect of Contrave on cardiac conduction
• clinical trials to evaluate dosing in patients with hepatic or renal impairment
• a clinical trial to evaluate the potential for interactions between Contrave and other drugs.

Contrave is distributed by Takeda Pharmaceuticals America of Deerfield, Ill. for Orexigen Therapeutics of La Jolla, Calif.