Indications and Usage Guidelines for Contrave (Naltrexone and Bupropion)
Contrave (naltrexone/bupropion extended-release) is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI of ≥30 kg/m² (obese) or ≥27 kg/m² (overweight) with at least one weight-related comorbidity such as hypertension, type 2 diabetes, or dyslipidemia. 1
Patient Selection Criteria
BMI requirements:
Weight-related comorbidities that qualify include:
- Type 2 diabetes mellitus
- Hypertension
- Dyslipidemia
- Obstructive sleep apnea 1
Mechanism of Action
Contrave combines two medications with complementary actions:
- Naltrexone (opioid receptor antagonist)
- Bupropion (dopamine and norepinephrine reuptake inhibitor)
This combination activates pro-opiomelanocortin (POMC) neurons in the arcuate nucleus, causing release of alpha-melanocyte-stimulating hormone, which projects to hypothalamic areas involved in weight control. 1
Dosage and Administration
Initial dose: Start with 1 tablet (naltrexone 8 mg/bupropion 90 mg) daily in the morning
Dose escalation: Increase by 1 tablet weekly according to this schedule:
- Week 1: 1 tablet daily (morning)
- Week 2: 1 tablet twice daily (morning and evening)
- Week 3: 2 tablets in morning, 1 tablet in evening
- Week 4 onward: 2 tablets twice daily (maximum dose of 32/360 mg daily) 1
Gradual titration is essential to minimize gastrointestinal side effects, particularly nausea 1, 3
Efficacy Assessment
- Evaluate weight loss at 12 weeks on the maintenance dose
- Discontinue if patient has not lost at least 5% of baseline body weight 1
- Expected weight loss: Approximately 4.8% greater than placebo at 56 weeks 1, 2
Contraindications
- Uncontrolled hypertension
- Seizure disorders or conditions that lower seizure threshold
- Use of other bupropion-containing products
- Current or prior diagnosis of bulimia or anorexia nervosa
- Chronic opioid use or during opiate withdrawal
- During or within 14 days of taking monoamine oxidase inhibitors (MAOIs)
- Pregnancy
- Severe hepatic impairment 1, 3
Precautions and Monitoring
- Blood pressure and heart rate: Monitor regularly, especially during dose escalation
- Psychiatric symptoms: Watch for emergence of suicidal thoughts, depression, or anxiety
- Seizure risk: Use with caution in patients with risk factors for seizures
- Angle-closure glaucoma: May precipitate an attack in susceptible individuals
- Hepatic impairment: Dose adjustment needed in moderate to severe impairment 1, 3
Common Side Effects
Drug Interactions
- Opioid medications: Contraindicated; may reduce efficacy of opioid pain medications
- MAOIs: Contraindicated; risk of hypertensive crisis
- CYP2B6 inhibitors/inducers: May affect bupropion levels
- Antihypertensive medications: May reduce efficacy 3
Important Clinical Considerations
- Contrave should always be used as an adjunct to lifestyle modifications, not as monotherapy 1
- Cardiovascular safety: Current evidence does not indicate increased risk of major adverse cardiovascular events with Contrave 4
- In patients with type 2 diabetes, Contrave has shown improvements in glycemic control in addition to weight loss 5
- The medication is approved for long-term use 1
Common Pitfalls to Avoid
- Failure to titrate properly: Rapid dose escalation increases side effects, particularly nausea
- Inadequate monitoring: Regular follow-up is essential, especially in the first 3 months
- Continuing ineffective therapy: Discontinue if 5% weight loss not achieved by 12 weeks
- Prescribing with contraindicated medications: Especially MAOIs and opioids
- Using as monotherapy: Always combine with reduced-calorie diet and increased physical activity
By following these guidelines, Contrave can be an effective tool for chronic weight management in appropriate patients when used as part of a comprehensive approach that includes lifestyle modifications.