Can I administer naltrexone (Naltrexone) and bupropion (Bupropion) separately?

Administering Naltrexone and Bupropion Separately

Naltrexone and bupropion should be administered as the FDA-approved combination product (naltrexone-bupropion ER) rather than as separate medications when used for weight management in patients with obesity or overweight with weight-related complications. 1

Rationale for Combination Product

• The FDA has approved the specific combination of naltrexone and bupropion as a sustained-release formulation containing 8 mg naltrexone and 90 mg bupropion per tablet for weight management 1
• The combination product has a synergistic mechanism of action that is specifically designed to enhance weight loss effects beyond what either medication can achieve individually 1, 2
• The combination targets both hedonic eating (through dopamine modulation and opioid receptor antagonism) and anorexigenic effects in the hypothalamus 1
• Bupropion alone has weak anorectic effects due to β-endorphin's auto-inhibitory activity on anorexigenic neurons, which naltrexone specifically counteracts 1

Dosing and Administration Considerations

• The naltrexone-bupropion ER combination follows a specific titration schedule:
  • Week 1: 1 tablet (8 mg naltrexone/90 mg bupropion) daily in the morning 1, 3
  • Week 2: 1 tablet twice daily 1, 3
  • Week 3: 2 tablets in morning, 1 tablet in afternoon 1, 3
  • Week 4 onward: 2 tablets twice daily (maintenance dose) 1, 3
• The second dose should not be taken late in the day to minimize insomnia risk 1, 3
• Dose adjustments are required for patients with renal or hepatic impairment:
  • Moderate to severe renal impairment: reduce to 1 tablet twice daily 1, 3
  • Moderate to severe hepatic impairment: do not exceed 1 tablet daily 1, 3
  • End-stage renal disease: avoid use 1

Efficacy and Safety Considerations

• In clinical trials, the combination product demonstrated 5.0-9.3% weight loss, with placebo-subtracted weight loss of 3.2-5.2% over 56 weeks 4
• The proportion of patients achieving ≥5% weight loss was 45-66% with the combination product 4
• Common adverse effects with the combination include:
  • Nausea (4.6-9.6%) 1, 4
  • Constipation 1, 4
  • Headache (0.9-1.8%) 1, 4
  • Dizziness (0.7-1.4%) 1, 4
• The combination product should be discontinued if patients haven't lost at least 5% of total body weight after 12 weeks on the maintenance dose 1, 3

Important Contraindications and Precautions

• Do not use in patients requiring opioid therapy as naltrexone can reduce analgesic efficacy or precipitate withdrawal 1, 3
• Discontinue before procedures requiring opioid use (e.g., endoscopies using fentanyl) 1
• Avoid in patients with epilepsy or uncontrolled hypertension 1, 3
• Use with caution in patients with history of seizures as bupropion may lower seizure threshold 1, 3
• Monitor vital signs regularly due to potential effects on blood pressure and heart rate 1, 3
• Avoid in patients treated with monoamine oxidase inhibitors or within 14 days of discontinuation 1

Additional Benefits for Specific Populations

• May be beneficial for patients with comorbid depression as bupropion has antidepressant effects 1, 3
• May assist with smoking cessation while mitigating associated weight gain 1
• Improves metabolic parameters including waist circumference, triglycerides, and insulin resistance 4