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FDA Approves Weight-Management Pill Contrave (Naltrexone/Bupropion)
The FDA has approved Contrave (naltrexone hydrochloride and bupropion hydrochloride, Takeda Pharmaceuticals America/Orexigen Therapeutics) as a 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 in adults with a BMI of 27 or greater (overweight) who have at least one weight-related condition, such as hypertension, type-2 diabetes, or high cholesterol (dyslipidemia).
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 clinical trials that included approximately 4,500 obese and overweight patients with and without significant weight-related conditions treated for 1 year. All of the patients received lifestyle modification consisting of a reduced- calorie diet and regular physical activity.
Results from a clinical trial that enrolled patients without diabetes showed that the patients had an average weight loss of 4.1% compared with placebo at 1 year. In this study, 42% of the patients treated with Contrave lost at least 5% of their body weight compared with 17% of the patients given placebo.
Results from another clinical trial that enrolled patients with type-2 diabetes showed that the patients had an average weight loss of 2% compared with placebo at 1 year. In this study, 36% of the patients treated with Contrave lost at least 5% of their body weight compared with 18% of the placebo-treated group.
In June, the FDA delayed its decision on the drug by 3 months because of concerns about adequate warnings on the packaging.
Because Contrave contains bupropion, the product labeling now includes a boxed warning to alert health care professionals and patients to the increased risk of suicidal thoughts and behaviors associated with antidepressant drugs. This warning also notes that serious neuropsychiatric events have been reported in patients taking bupropion for smoking cessation.
In addition, Contrave can cause seizures and must not be used in patients who have seizure disorders. The risk of seizure is dose-related. The drug can also raise blood pressure and heart rate and must not be used in patients with uncontrolled hypertension.
The most common adverse events reported with Contrave include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.
According to Reuters, weight-loss drugs face reimbursement challenges. Government and private health insurers are reluctant to cover Belviq (lorcaserin, Eisai) and Qsymia (phentermine/topiramate, Vivus, Inc.), unconvinced of their long-term efficacy since patients often withdraw from treatment.
“For all the obesity drugs that are out there, only 30 to 40 percent of the health maintenance organizations pay for obesity coverage,” a market analyst said.
The FDA is requiring several post-marketing evaluations of Contrave:
- A cardiovascular outcomes trial to assess the cardiovascular risk associated with use of the drug
- Two efficacy, safety, and clinical pharmacology studies in pediatric patients (one in patients 7 to 11 years of age, and the other in patients 12 to 17 years of age)
- A nonclinical (animal) juvenile toxicity study with a focus on growth and development as well as on 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