Naltrexone-Bupropion Combination Therapy with Phentermine, Lorazepam, and Ambien

Critical Safety Considerations

The American College of Cardiology recommends careful cardiovascular and seizure risk monitoring when prescribing naltrexone with phentermine, lorazepam, and zolpidem, as the combination can increase the risk of seizures and cardiovascular events 1, 2, 4
The patient must remain on a stable lorazepam dose throughout naltrexone-bupropion treatment to avoid the risk of abrupt benzodiazepine discontinuation, which can increase seizure risk 1
Current opioid use is an absolute contraindication for naltrexone-bupropion, as naltrexone blocks opioid receptors 1, 2
Seizure disorders or conditions predisposing to seizures are absolute contraindications for naltrexone-bupropion, as the bupropion component lowers the seizure threshold 1, 2, 3
Uncontrolled hypertension is an absolute contraindication for naltrexone-bupropion, as the combination can increase blood pressure and heart rate 1, 2

Baseline blood pressure and heart rate measurement are required before initiating therapy, with periodic monitoring every 12 weeks for the first 3 months, and ongoing monitoring throughout treatment 1, 2
Liver function tests are required every 3-6 months during long-term naltrexone treatment, with more frequent monitoring if naltrexone doses exceed 50 mg/day 1, 2
Close monitoring for mood changes, suicidal ideation, and behavioral changes is required, particularly in the first months of treatment, as bupropion carries a black box warning for increased suicidal thoughts in young adults under 24 years 1, 2

The recommended titration schedule for naltrexone-bupropion is to start with 8 mg/90 mg once daily in the morning for the first week, increasing to 8 mg/90 mg twice daily in the second week, and then to 16 mg/180 mg in the morning and 8 mg/90 mg in the evening in the third week, with a target dose of 16 mg/180 mg twice daily (total daily: 32 mg/360 mg) by the fourth week 2, 4

Patients can expect a weight loss of approximately 6.1% at 56 weeks, with 44.5-48% of patients achieving ≥5% body weight loss 2
The bupropion component may also improve anxiety symptoms, and weight loss may lead to a reduction in insomnia 2