FDA Approves Combination Adjunct Therapy for Chronic Weight Management in Obese Adults

Extended-release naltrexone hydrochloride and bupropion hydrochloride (Contrave) has been approved as an adjunct therapy for chronic weight management in obese adults.

The FDA has approved naltrexone hydrochloride and bupropion hydrochloride (Contrave) extended-release tablets as an adjunct to reduced-calorie diet and increased physical activity for chronic weight management in obese adults.

According to the drug’s developer, Orexigen Therapeutics, and distributor, Takeda Pharmaceuticals America, the cardiometabolic product is indicated for use in adults with a body mass index (BMI) of at least 27 who have at least 1 weight-related condition, such as hypertension, type 2 diabetes, or dyslipidemia.

“Some individuals seeking to manage their weight may require a treatment plan that includes more than lifestyle modification with diet and exercise,” said Ken Fujioka, MD, director of the Center for Weight Management in the Division of Diabetes and Endocrinology at Scripps Clinic, in a joint press release from Orexigen and Takeda. “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.”

According to the US Centers for Disease Control and Prevention, more than one-third of adults in the United States are obese.

“Obesity continues to be a major public health concern,” said Jean-Marc Guettier, MD, director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, in an FDA press release. “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 1 weight-related health condition.”

Contrave is comprised of 2 FDA-approved drugs, naltrexone and bupropion, in an extended-release formulation. As stand-alone therapies, naltrexone is indicated to treat alcohol and opioid dependence, while bupropion is indicated to treat depression and seasonal affective disorder, as well as to aid smoking cessation treatment.

The effectiveness of the 2 drugs combined was evaluated in multiple clinical trials that included approximately 4,500 obese and overweight patients with and without significant weight-related conditions treated for 1 year. In the trials, all patients received lifestyle modification consisting of a reduced-calorie diet and regular physical activity.

Results from 1 clinical trial showed that 42% of patients without diabetes who were treated with Contrave lost at least 5% of their body weight, compared to 17% of those treated with placebo. Similarly, results from another clinical trial that enrolled patients with type 2 diabetes found 36% of those treated with Contrave lost at least 5% of their body weight, compared to 18% of the placebo group.

Across the trials, the most common adverse reactions reported with Contrave treatment were nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.

The FDA warned that the drug can cause seizures, raise blood pressure, and increase heart rate, so it is contraindicated in patients who have seizure disorders or uncontrolled hypertension. Because Contrave contains bupropion, it should not be taken with other medications containing bupropion, the FDA said. Additionally, the drug 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 part of the drug’s approval, Takeda and Orexigen have agreed to fulfill several post-marketing requirements, which include conducting studies to assess the safety and efficacy of Contrave for weight management in obese pediatric patients, and to evaluate the effects of long-term Contrave treatment on the incidence of major adverse cardiovascular events in overweight and obese subjects with cardiovascular disease or multiple cardiovascular risk factors.

In the meantime, the FDA said patients taking the maintenance dose of Contrave should be evaluated after 12 weeks to determine whether or not the treatment is effective. If a patient has not lost at least 5% of his or her baseline body weight, then the drug should be discontinued, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment.