What is the typical dosing regimen for Contrave (naltrexone-bupropion) for weight loss?

Contrave Dosing for Weight Loss

Standard Titration Schedule

Contrave (naltrexone 8 mg/bupropion 90 mg per tablet) requires a 4-week dose escalation to reach the target maintenance dose of 2 tablets twice daily (total daily dose: naltrexone 32 mg/bupropion 360 mg). 1, 2

The gradual titration schedule minimizes adverse effects, particularly nausea, which affects approximately 30% of patients:

• Week 1: 1 tablet once daily in the morning 1, 2
• Week 2: 1 tablet twice daily (morning and evening) 1, 2
• Week 3: 2 tablets in the morning and 1 tablet in the evening 1, 2
• Week 4 and beyond: 2 tablets twice daily (maintenance dose) 1, 2

This represents a total daily dose of naltrexone 32 mg/bupropion 360 mg at maintenance. 1, 3

Efficacy Assessment and Discontinuation Criteria

The medication should be discontinued if 5% weight loss is not achieved after 12 weeks at the maintenance dose. 1, 2

Expected outcomes with Contrave include:

• Mean weight loss of 5.0-9.3% from baseline, with placebo-subtracted weight loss of 3.2-5.2% over 56 weeks 3
• Approximately 45-66% of patients achieve ≥5% weight loss (placebo-subtracted proportion: 23-34%) 3
• Additional benefits include decreased waist circumference, reduced serum triglycerides, improved insulin resistance, and increased HDL-cholesterol 3

Critical Contraindications and Safety Considerations

Absolute contraindications include:

• Uncontrolled hypertension (bupropion can increase blood pressure and heart rate) 2
• History of seizures or conditions predisposing to seizures (bupropion lowers seizure threshold) 1, 2
• Current use of MAOIs or within 14 days of discontinuing MAOIs 4
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 4
• Pregnancy or planning pregnancy 2
• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk 4

Common Adverse Effects and Management

The most frequent side effects are gastrointestinal and neurological:

• Nausea (most common, affecting ~30% of patients), constipation, vomiting, headache, dizziness, and dry mouth 3, 5
• These effects are typically transient and can be minimized through gradual dose escalation 1
• Blood pressure may show a transient increase of ~1.5 mm Hg followed by reduction below baseline 5
• Heart rate may increase slightly, requiring monitoring 2

Critical timing consideration: The second daily dose should be taken before 3 PM to minimize insomnia risk, as bupropion has activating properties. 4

Special Population Dose Adjustments

For hepatic impairment (moderate to severe): Maximum total daily dose should not exceed 1 tablet once daily (naltrexone 8 mg/bupropion 90 mg). 4

For renal impairment (moderate to severe, GFR <90 mL/min): Reduce total daily dose by half, as bupropion and its metabolites are cleared renally and may accumulate. 4

Cardiovascular Safety Profile

Systematic review evidence demonstrates no increased risk of major adverse cardiovascular events (MACE) with naltrexone/bupropion combination compared to placebo or active comparators, with differences in MACE proportions not exceeding 2.5%. 6 However, patients should still be monitored for blood pressure and heart rate changes. 2

Clinical Context

Contrave must be used as an adjunct to comprehensive lifestyle intervention including reduced-calorie diet and increased physical activity—not as monotherapy. 1, 3 The combination works synergistically by activating POMC neurons in the arcuate nucleus, leading to release of alpha-melanocyte-stimulating hormone, which regulates feeding and body weight control. 1