Contrave Naltrexone Dosage
Contrave contains 8 mg of naltrexone hydrochloride per tablet, combined with 90 mg of bupropion hydrochloride in an extended-release formulation. 1, 2
Dosing Schedule and Titration
The maintenance dose of Contrave for obesity management is 32 mg naltrexone/360 mg bupropion daily, which translates to 4 tablets per day (2 tablets twice daily) 1, 3
Week-by-Week Titration Protocol
- Week 1: 8 mg naltrexone/90 mg bupropion once daily in the morning (1 tablet AM) 3
- Week 2: 8 mg naltrexone/90 mg bupropion twice daily (1 tablet AM, 1 tablet PM) 3
- Week 3: 16 mg naltrexone/180 mg bupropion in the morning and 8 mg naltrexone/90 mg bupropion in the evening (2 tablets AM, 1 tablet PM) 3
- Week 4 and beyond: 16 mg naltrexone/180 mg bupropion twice daily (2 tablets AM, 2 tablets PM) - this is the maintenance dose 3
Clinical Efficacy Data
The fixed-dose combination demonstrated statistically significant weight loss across four Phase III trials (COR-I, COR-II, COR-BMOD, COR-DM) involving 4,536 participants, with average weight loss of approximately 11-22 lbs (5-9 kg) over 52-56 weeks 4
In the COR-I trial specifically, 48% of participants on the 32 mg naltrexone/360 mg bupropion dose achieved ≥5% weight loss compared to 16% on placebo 5
Critical Safety Considerations
Absolute Contraindications
- Chronic opioid therapy or opioid dependence - naltrexone will precipitate severe withdrawal 3, 2
- Uncontrolled hypertension - both components can elevate blood pressure 1, 3
- Seizure disorders or conditions predisposing to seizures - bupropion lowers seizure threshold 1, 3
- Pregnancy - contraindicated in women who are or may become pregnant 3
- Eating disorders (bulimia or anorexia nervosa) - increased seizure risk 3
- Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs - dramatically increases seizure risk 3
- Current or recent MAOI use (within 14 days) 1
Dose Adjustments for Organ Impairment
- Moderate to severe hepatic impairment: Maximum dose is 8 mg naltrexone/90 mg bupropion once daily (1 tablet daily) 1, 3
- Moderate to severe renal impairment: Reduce total daily dose by 50% 1, 3
Monitoring Requirements
- Blood pressure and heart rate: Monitor periodically, especially during the first 12 weeks, as transient increases of approximately 1.5 mm Hg may occur initially 1, 3, 5
- Efficacy assessment: If <5% weight loss at 12 weeks, discontinue and consider alternative treatment 1
- Neuropsychiatric symptoms: Monitor for suicidal ideation, particularly in patients under 24 years old 3
Common Pitfalls to Avoid
Do not prescribe Contrave without confirming the patient is not taking any opioid medications, including partial agonists like buprenorphine - this is an absolute contraindication 3
Do not administer the second dose late in the day - give before 3 PM to minimize insomnia risk from the bupropion component 3
Do not exceed the maximum dose of 32 mg naltrexone/360 mg bupropion daily to maintain seizure risk at approximately 0.1% 3, 5
The most common adverse events are nausea (29.8%), headache, constipation, dizziness, vomiting, and dry mouth, with nausea being significantly more frequent than placebo (5.3%) 5