From the Guidelines
Naltrexone/bupropion for weight loss should be initiated with a gradual dose escalation over 4 weeks, starting with one tablet (8 mg naltrexone/90 mg bupropion) taken once daily in the morning for the first week, as recommended by the most recent guidelines 1.
Dosing Schedule
The dosing schedule for naltrexone/bupropion is as follows:
- Week 1: 1 tablet (8 mg naltrexone/90 mg bupropion) PO QAM
- Week 2: 1 tablet (8 mg naltrexone/90 mg bupropion) PO QAM and 1 tablet (8 mg naltrexone/90 mg bupropion) PO QHS
- Week 3: 2 tablets (16 mg naltrexone/180 mg bupropion) PO QAM and 1 tablet (8 mg naltrexone/90 mg bupropion) PO QHS
- Week 4: 2 tablets (16 mg naltrexone/180 mg bupropion) PO BID
Mechanism of Action
The medication works through dual mechanisms: naltrexone blocks opioid receptors while bupropion affects dopamine and norepinephrine reuptake, together reducing hunger and food cravings 1.
Important Considerations
- Take with food and avoid evening doses close to bedtime as bupropion may cause insomnia
- Combine with calorie reduction and increased physical activity for optimal results
- Treatment should be discontinued if 5% weight loss is not achieved after 12 weeks at the maintenance dose
- Patients with certain conditions, including uncontrolled hypertension, seizure disorders, or eating disorders, should avoid this medication combination 1
Side Effects and Safety Concerns
Common side effects include nausea, headache, and constipation, while safety concerns include increased heart rate and blood pressure, and potential for seizures 1
From the Research
Naltrexone and Bupropion Dosing for Weight Loss
- The combination of 32 mg naltrexone and 360 mg bupropion prolonged release (NB32) was approved by the FDA and EMA as an adjunct to a comprehensive lifestyle intervention for weight loss 2.
- The recommended dosing for naltrexone and bupropion is 32 mg and 360 mg per day, respectively, in fixed-dose tablets 3.
- A 3-week dose escalation is recommended for naltrexone and bupropion treatment 3.
- The efficacy and safety of naltrexone/bupropion were assessed in four randomized, double-blind, placebo-controlled, 56-week Phase III clinical trials, which demonstrated statistically significant and clinically meaningful weight loss following up to 52 weeks of treatment 4.
Efficacy of Naltrexone and Bupropion for Weight Loss
- NB32 treatment resulted in 5.0-9.3% weight loss, while the placebo-subtracted weight loss was 3.2-5.2% during 56 weeks of treatment 2.
- The proportion of treated patients with ≥ 5% weight loss was 45-66%, while the placebo-subtracted proportion was 23-34% 2.
- The average weight loss from baseline across four studies was approximately 11-22 lbs (5-9 kg) 4.
- Naltrexone/bupropion treatment was associated with a decrease in waist circumference, serum triglycerides, and insulin resistance, and an increase in high-density lipoprotein-cholesterol (HDL-C) 2.
Safety of Naltrexone and Bupropion for Weight Loss
- The most common side effects of naltrexone and bupropion treatment were nausea, constipation, headache, and vomiting 2, 3.
- Serious adverse effects, which were very rare, included suicidal thoughts and seizures 2.
- Naltrexone/bupropion treatment was well tolerated by the majority of patients, with few reports of side effects 5.
- A transient increase in mean systolic and diastolic blood pressure was followed by a reduction below baseline in the naltrexone plus bupropion groups 3.