FDA Approves Contrave for Weight Loss in Obese Adults

The FDA has approved Contrave (naltrexone HCI and bupropion HCI) extended-release tablets as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults 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 one weight-related comorbid condition, such as hypertension, type 2 diabetes, or dyslipidemia.

Developed by Orexigen Therapeutics, and distributed by Takeda Pharmaceuticals America, Contrave is an extended-release formulation that combines naltrexone (approved by the FDA as a stand-alone product to treat alcohol and opioid dependence) and bupropion (approved by the FDA as a standalone product to treat depression and seasonal affective disorder and as an aid to smoking cessation treatment).

According to Jean-Marc Guettier, MD, director of the Division of Metabolism and Endocrinology Products in FDA’s Center for Drug Evaluation and Research, “Obesity continues to be a major public health concern. 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 was approved based on results from a series of clinical trials that enrolled nearly 4,500 obese and overweight patients with and without significant weight-related conditions who were treated for one year. All participants received lifestyle modification that consisted of a reduced- calorie diet and regular physical activity.

In one clinical trial that enrolled patients who were not diagnosed with diabetes, participants had an average weight loss of 4.1 percent over treatment with placebo at one year. Forty-two percent of patients treated with Contrave lost at least 5 percent of their body weight, compared with 17 percent 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 2 percent over treatment with placebo at one year. In this trial, 36 percent of patients treated with Contrave lost at least 5 percent of their body weight, compared with 18 percent of patients treated with placebo.

The most common adverse reactions reported in patients taking Contrave in the trials included nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.

In a news release from Orexigen and Takeda, Ken Fujioka, MD, director of the Center for Weight Management in the Division of Diabetes and Endocrinology at Scripps Clinic, said “Some individuals seeking to manage their weight may require a treatment plan that includes more than lifestyle modification with diet and exercise. In my clinic, I often treat patients who fit these criteria, and now, with the approval of Contrave, I am excited to have a new treatment option to consider for my patients.”

The FDA noted that because it contains bupropion, “Contrave has a boxed warning to alert health care professionals and patients to the increased risk of suicidal thoughts and behaviors associated with antidepressant drugs. The warning also notes that serious neuropsychiatric events have been reported in patients taking bupropion for smoking cessation.”

Contrave can cause seizures, raise blood pressure, and increase heart rate, and should not be administered to patients who have seizure disorders or uncontrolled hypertension. Because Contrave contains bupropion, it should not be taken with other medications containing bupropion.

Contrave has a boxed warning to alert health care professionals and patients to the increased risk of suicidal thoughts and behaviors associated with antidepressant drugs. The warning also notes that serious neuropsychiatric events have been reported in patients taking bupropion for smoking cessation.

Contrave should not be used in patients who have eating disorders, are using opioids or treatments for opioid dependence, or are undergoing an abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs.

As a condition of Contrave’s approval, Orexigen and Takeda have agreed to conduct “several post-marketing requirements, including studies to assess the safety and efficacy of Contrave for weight management in obese pediatric patients. There will also be a new randomized double-blind, placebo-controlled study to evaluate the effects of long-term treatment with Contrave on the incidence of major adverse cardiovascular (CV) events in overweight and obese subjects with CV disease or multiple CV risk factors.”

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 percent 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.