How should the fixed‑dose combination tablet of naltrexone and bupropion be taken?

How to Take Naltrexone-Bupropion

Naltrexone-bupropion ER should be started at 1 tablet (8 mg naltrexone/90 mg bupropion) each morning, then escalated weekly over 4 weeks to reach the maintenance dose of 2 tablets twice daily (total daily dose: 32 mg naltrexone/360 mg bupropion). 1

Titration Schedule

The medication requires a gradual dose escalation to minimize side effects, particularly nausea:

• Week 1: 1 tablet in the morning
• Week 2: 1 tablet twice daily (morning and afternoon)
• Week 3: 2 tablets in the morning + 1 tablet in the afternoon
• Week 4 onward: 2 tablets twice daily (morning and afternoon) - maintenance dose

1

Administration Instructions

• Swallow tablets whole - do not crush, divide, or chew them, as this is a sustained-release formulation 1
• Take the second dose earlier in the day (not late afternoon/evening) to minimize insomnia risk 1
• Can be taken with or without food 2
• If you miss a dose, do not double up - just take the next scheduled dose 2

Dose Adjustments for Special Populations

Renal impairment (moderate to severe):

• Reduce to 1 tablet twice daily (half the standard maintenance dose)
• Avoid completely in end-stage renal disease 1

Hepatic impairment:

• Moderate to severe (Child-Pugh 7-15): Maximum 1 tablet daily
• Mild (Child-Pugh 5-6): Consider dose reduction 1

Evaluating Treatment Response

After 12 weeks on the full maintenance dose, assess weight loss 1:

• If the patient has not lost at least 5% of total body weight, discontinue the medication - they are likely a poor responder
• This is a critical decision point to avoid continuing ineffective treatment

Critical Safety Considerations

Must discontinue before procedures requiring opioids (e.g., endoscopies with fentanyl) due to the naltrexone component blocking opioid effects 1

Absolute contraindications:

• Current or anticipated need for short-term or long-term opioid therapy (will precipitate withdrawal or block analgesic effects) 1
• Seizure disorders or epilepsy (bupropion lowers seizure threshold) 1
• Uncontrolled hypertension 1
• Use of MAO inhibitors within 14 days 2

Monitor closely:

• Blood pressure and heart rate, especially in the first 8-12 weeks (modest increases may occur initially) 1
• Neuropsychiatric symptoms including suicidal thoughts, particularly in patients under 24 years old 1

Common Side Effects During Titration

The buildup phase is when most side effects occur 1:

• Nausea (most common: 29.8% vs 5.3% placebo) - gradual titration helps mitigate this
• Headache (19.4%)
• Constipation (28.6%)
• Vomiting
• Dizziness

These effects are the primary reason for the 4-week titration schedule rather than starting at full dose immediately.

When to Discontinue

If discontinuing after reaching the 300 mg bupropion daily dose (2 tablets twice daily), taper down to 150 mg daily (1 tablet twice daily) before stopping completely to avoid withdrawal symptoms 1, 2