Contrave (Naltrexone-Bupropion ER) for Obesity Management
Primary Indication
Contrave is indicated as an adjunct to lifestyle modifications (reduced-calorie diet and increased physical activity) for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity such as type 2 diabetes, hypertension, or dyslipidemia. 1, 2
Mechanism of Action
- Contrave combines naltrexone 8 mg and bupropion 90 mg in sustained-release formulation, working synergistically on the hypothalamic appetite regulation system 2
- Bupropion stimulates proopiomelanocortin (POMC) neurons in the arcuate nucleus while naltrexone blocks opioid-mediated autoinhibition of these neurons, reducing food cravings and improving dysregulation of eating control in mesolimbic pathways 1, 2
Dosing Protocol
Start with one 8mg/90mg tablet daily in the morning and increase by one tablet per week until reaching the target dose of two tablets twice daily (total daily: naltrexone 32 mg/bupropion 360 mg). 3, 2
- This gradual titration minimizes adverse effects including nausea, constipation, headache, and dizziness 3
- Discontinue treatment if the patient has not achieved at least 5% weight loss after 12 weeks at maximum dose, as continued use is unlikely to provide meaningful benefit. 3, 2
Expected Weight Loss Efficacy
- Mean weight loss of approximately 4.8-6.0% at 56 weeks compared to placebo 1, 2
- 36-57% of patients achieve ≥5% total body weight loss 2
- Weight loss is less than phentermine-topiramate (6.7-8.9 kg) and liraglutide (5.8-5.9 kg), but allows for long-term use unlike short-term phentermine 1, 3
Absolute Contraindications
Do not prescribe Contrave in patients with: 1, 3, 2
- Uncontrolled hypertension
- Seizure disorders or conditions that increase seizure risk
- Current opioid use (naltrexone will precipitate withdrawal in opioid-dependent individuals) 3
- Eating disorders (anorexia nervosa or bulimia nervosa)
- Pregnancy or women not using reliable contraception 3
- Use of MAO inhibitors within 14 days 2
- History of cardiovascular disease (use with caution, though Contrave does not show increased cardiovascular risk unlike phentermine) 3
Monitoring Requirements
Monitor blood pressure and heart rate periodically, especially during the first 12 weeks of treatment, as Contrave can elevate both parameters. 1, 3
- Assess weight loss at 12 weeks to determine continuation 3
- Monitor for neuropsychiatric symptoms given bupropion component 2
Preferred Patient Populations
Contrave may be particularly beneficial for: 1, 2
- Patients with obesity and comorbid depression (bupropion is the only antidepressant consistently shown to promote weight loss) 2
- Patients attempting smoking cessation 1
- Patients seeking alcohol use reduction 1, 2
- Patients transitioning from short-term phentermine who need long-term weight management 3
Common Adverse Effects
- Nausea (29.8% of patients) is the most common adverse effect 2, 4
- Constipation, headache, vomiting, dizziness, and dry mouth are also frequently reported 2, 4
- Gradual dose escalation helps mitigate these effects 3
Cardiovascular Safety Profile
Available evidence does not indicate an increased risk of major adverse cardiovascular events (MACE) with Contrave use. 5
- Systematic review of 70 studies found no increased MACE risk compared to placebo or active comparators 5
- The difference in MACE proportions between Contrave and comparators did not exceed 2.5% 5
Switching from Phentermine
Discontinue phentermine immediately and start Contrave the next day using the standard dose escalation protocol, as there is no pharmacological requirement for a washout period. 3