Approved for long-term weight management in patients with obesity.
Bupropion is a dopamine/norepinephrine reuptake inhibitor approved for depression and for smoking cessation.
Naltrexone Opioid receptor antagonist
Bupropion Norepinephrine-dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist
Trade names Contrave, Mysimba
Routes of administration By mouth
Naltrexone/bupropion, is a fixed-dose combination medication for the management of chronic obesity in adults in combination with a reduced-calorie diet and increased physical activity.
Both medications have individually shown some evidence of effectiveness in weight loss, and the combination has been shown to have some synergistic effects on weight.
Naltrexone/bupropion is indicated, as an adjunct to a reduced-calorie diet and increased physical activity, as anti-obesity medication for the management of weight in adults with an initial body mass index (BMI) of:
30 kg/m2 (obese), or 27 kg/m2 to < 30 kg/m2, (overweight) in the presence of one or more weight-related comorbidities, like type 2 diabetes, dyslipidaemia, or controlled high blood pressure.
Each tablet contains 8 mg naltrexone and 90 mg bupropion.
Once full dosing is reached after 4 weeks of administration, the total dosage for treating overweight or obesity is two tablets twice daily or 32 mg naltrexone and 360 mg bupropion per day.
Naltrexone/bupropion is contraindicated in patients who have/are:
History of seizures History of an eating disorder such as bulimia nervosa or anorexia nervosa Taking opioids, or are in opiate withdrawal. Taken monoamine oxidase inhibitors in the last 14 days Pregnant Abruptly stopped use of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
There is a boxed warning regarding an increased risk for suicidal thoughts and behavior in children, adolescents, and young adults under the age of 25.
This is attributed to the bupropion component.
The safety and effectiveness of Naltrexone/bupropion in children under the age of 18 has not been studied.
Individually, naltrexone and bupropion each target pathways in the central nervous system that influence appetite and energy use.
Bupropion is a reuptake inhibitor of both norepinephrine and dopamine, and a nicotinic acetylcholine receptor antagonist.
Bupropion activates proopiomelanocortin (POMC) neurons in the hypothalamus which give an effect downstream, resulting in loss of appetite and increased energy output.
Proopiomelanocortin (POMC) neurons is regulated by endogenous opioids via opioid-mediated negative feedback.
Naltrexone is a pure opioid antagonist, which further augments bupropion’s activation of the proopiomelanocortin (POMC) neurons .
Combined, naltrexone/bupropion affects the reward pathway which results in reduced food cravings.
Naltrexone is an opioid receptor antagonist approved to treat alcohol and opioid dependence.
Bupropion in obesity studies is associated with a 2.8 kg plecebo-subtracted weight-loss at 6 to 12 months.
Bupropion is suspected to stimulate secretion of anorexigenic alpha-melanocyte-stimulating hormone from pro opiomelanocortin-producing hypothalamic cells.
Naltrexone has little efficacy in weight management as a single agent, however it counteracts the auto inhibitory reactions of bupropion stimulated endogenous opioids.
Naltrexone and bupropion reduce appetite and food cravings through different mechanisms that stimulate propriomelanocortin neurons.
Randomized control studies including 9949 adults with obesity found the combination of agents associated with a 4.1% greater weight loss than placebo.
Combining naltrexone with bupropion and intensive behavioral therapy is associated with a 9.3% weight loss at 12 months compared with 5.1% weight loss for placebo with intensive behavioral therapy.
Naltrexone and bupropion have fewer cardiac effects on risk factors than does some other anti-obese medications.
Common and effects of N-B include nausea, constipation, headache, vomiting, dizziness, insomnia, and xerostomia.