The U.S. Food and Drug Administration (FDA) has given the nod to La Jolla, California-based Orexigen Therapeutics’ naltrexone hydrochloride and bupropion hydrochloride extended-release tablets (Contrave). Contrave is a treatment for chronic weight management in addition to a reduced-calorie diet and physical activity. Takeda Pharmaceuticals America will distribute the drug.
The drug is approved for use in adults with a body mass index (BMI) of 30 or greater (considered obese), and in adults with a BMI of 27 or greater (considered overweight) who have at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol.
BMI, which measures body fat based on an individual’s weight and height, is used to define the obese and overweight categories.
Contrave Joins Two Other New Obesity Drugs
According to the Centers for Disease Control and Prevention (CDC), more than one-third of adults in the United States, or 78.6 million people, are obese. Obesity-related conditions include heart disease, stroke, type 2 diabetes, and certain types of cancer, all leading causes of preventable death.
Contrave is the third prescription weight loss drug to receive FDA approval in the past two years, after more than 13 years without a new drug in this category. Arena Pharmaceuticals’ lorcaserin hydrochloride (Belviq) was approved in June 2012, and Vivus’ phentermine and topiramate extended-release tablets (Qsymia) were cleared in July 2012.
Dr. Jean-Marc Guettier, director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, said in a press statement, “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.”
Contrave Is a Combination of Two Addiction Drugs
Contrave is a combination of two FDA-approved drugs, naltrexone and bupropion, in an extended-release formula. Naltrexone treats alcohol and opioid dependence. Bupropion is used to treat depression and seasonal affective disorder and as an aid to help people quit smoking.
Contrave was studied in multiple clinical trials involving about 4,500 obese and overweight patients with and without significant weight-related conditions. Patients were treated for one year. They were provided with lifestyle modifications, including a reduced-calorie diet and regular physical activity.
A clinical trial that enrolled patients without diabetes revealed that patients on Contrave had a 4.1 percent greater average weight loss than patients who received a placebo after one year. In this trial, 42 percent of patients treated with Contrave lost at least 5 percent of their body weight, compared with 17 percent of patients treated with a placebo.
In another trial of type 2 diabetes patients, patients had a greater average weight loss of 2 percent over treatment with placebo at the one year mark. In this trial, 36 percent of patients treated with Contrave lost at least 5 percent of their body weight, compared to 18 percent of patients treated with a placebo.
A Diabetes Expert Weighs In
Dr. Ronald Tamler, director of the Mount Sinai Diabetes Center at the Mount Sinai Hospital in New York City told Healthline, “The new drug increases the options that we clinicians have in treating obesity, a condition that now affects a third of all adults in the United States. This drug addresses our addiction to overeating.
"While medications, such as this one, are useful alternatives, I recommend starting with the least expensive and most-proven option with zero side effects, which is sustainable lifestyle changes in conjunction with your doctor and a dietician,” he added.
Tamler went on to say that another sustainable option for severely overweight patients is weight-loss surgery, “which has been shown to increase life expectancy, decrease diabetes, cancer, heart disease, and many other ailments.”
Warnings and Directions for Contrave
According to the FDA, patients using Contrave at the maintenance dose should be evaluated after 12 weeks to see if the treatment is working. If a patient has not lost at least 5 percent of his or her body weight, Contrave should be discontinued, as it is unlikely that the patient will achieve and sustain weight loss with continued drug treatment.
Because it contains bupropion, Contrave has a boxed warning to alert doctors 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 also raise blood pressure and heart rate and must not be used in patients with uncontrolled high blood pressure, according to the FDA.
The most common adverse reactions reported with Contrave include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.
The FDA is planning numerous post-marketing follow-up studies to test Contrave in younger patients and in patients with other chronic conditions.