The FDA today approved Contrave — combination naltrexone hydrochloride and bupropion hydrochloride extended-release tablets — as an adjunct to a reduced-calorie diet and physical activity for chronic weight management, according to a press release from the agency.
Contrave is approved for use in adults with obesity, defined as a BMI of at least 30, or adults with overweight, defined as a BMI of at least 27, who have at least one weight-related comorbidity, such as hypertension, type 2 diabetes or dyslipidemia.
Currently, naltrexone is approved for treatment of alcohol and opioid dependence, and bupropion is approved for treatment of depression and seasonal affective disorder, and as an aid to smoking cessation treatment.
Researchers evaluated the drug in multiple clinical trials that included about 4,500 obese and overweight patients with and without significant weight-related conditions. Patients were treated for 1 year, and all received lifestyle medication comprised of a reduced-calorie diet and regular physical activity.
In a clinical trial involving patients without diabetes, results showed that 42% of patients treated with Contrave lost at least 5% of their body weight vs. 17% of patients treated with placebo.
In another clinical trial enrolling patients with type 2 diabetes, results showed that 36% of those treated with Contrave lost at least 5% of their body weight vs. 18% of patients treated with placebo.
Clinicians should evaluate patients using Contrave at the maintenance dose after 12 weeks to establish that the treatment is effective, according to the release, and the drug should be discontinued if the patient has not lost at least 5% of baseline body weight.
Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth and diarrhea were the most commonly reported adverse reactions.
Seizures may also be caused by Contrave, and the drug is therefore not appropriate for patients with seizure disorders. According to the release, seizure risk is dose-related, and use should be discontinued permanently in those who experience a seizure while on treatment.
The drug has also been associated with increases in blood pressure and heart rate and should not be used in patients with uncontrolled hypertension.
Patients should not use other products containing bupropion while being treated with Contrave, the agency noted. The drug should also not be used in the following patients: those using opioids or treatments for opioid dependence or who are undergoing acute opiate withdrawal; those undergoing an abrupt discontinuation of alcohol, benzodiazepines, barbiturates and antiepileptic drugs; and women who are pregnant or trying to become pregnant.
“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 condition,” Jean-Marc Guettier, MD, director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, said in the release.
Contrave is distributed by Takeda Pharmaceuticals America Inc. for Orexigen Therapeutics Inc.
| Expert Opinion
Statement from The Obesity Society
Lee Kaplan, MD, PhD
As the number of Americans affected by severe obesity continues to rise, equipping our nation’s doctors with proven and effective tools to treat patients for this disease is increasingly important. Today’s FDA announcement that Contrave (combination of naltrexone sustained release [SR] and bupropion SR) has been approved for long-term treatment of obesity is an important step toward this goal and can help improve the health and weight of our nation.
The Obesity Society (TOS) researchers and clinicians agree: losing weight solely by altering lifestyle changes, while effective for some people, can often be difficult to accomplish, and even more difficult to maintain. Additional treatment strategies, such as antiobesity medications like Contrave, are important tools in the clinician’s toolbox for treating obesity.
The Society supports more research and continued efforts to develop weight loss and weight maintenance strategies that are more effective for a larger patient population. One means of doing so is to increase in the number of safe and effective antiobesity medications. Obesity is a complex, chronic disease, and continued work to understand the science of this disorder will facilitate the development of additional effective treatments, bringing us closer to slowing, stopping and ultimately reversing this epidemic.
Advancements in drug and other medical therapies can substantially improve obesity-related metabolic comorbidities and reduce costs. As clinicians work to integrate these new tools into practice, we all must keep in mind that they are intended for use in combination with proven lifestyle modifications, including healthier diets, regular physical activity and efforts to reduce chronic stress, improve sleep and support healthy circadian rhythms.
Lee Kaplan, MD, PhD, Fellow of The Obesity Society
Chair, Clinical Committee, The Obesity Society
Director, Obesity, Metabolism and Nutrition Institute
Massachusetts General Hospital