What is Trivellix (naltrexone and bupropion)?

What is Trivellix (Naltrexone and Bupropion)?

Trivellix is a combination medication containing naltrexone and bupropion in an extended-release formulation that is FDA-approved for the treatment of obesity. 1

Mechanism of Action

• Naltrexone is an opioid antagonist that is FDA-approved for the treatment of alcohol and opioid dependence 1
• Bupropion is a dopamine and norepinephrine reuptake inhibitor that is FDA-approved as an antidepressant and to assist with smoking cessation 1
• The combination works by modulating central reward pathways triggered by food, with naltrexone antagonizing an inhibitory feedback loop that would otherwise limit bupropion's appetite-suppressing properties 1
• Together, they activate pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus, promoting release of α-melanocyte-stimulating hormone, an anorectic neuropeptide involved in body weight regulation 1

Clinical Efficacy

• In clinical trials, naltrexone/bupropion demonstrated 5.0-9.3% weight loss, with placebo-subtracted weight loss of 3.2-5.2% during 56 weeks of treatment 2
• In the 56-week COR-I trial, weight loss of 6.1% was observed in patients assigned to naltrexone/bupropion compared to 1.3% with placebo 1
• 44.5-66% of patients receiving naltrexone/bupropion lost ≥5% of their body weight after 56 weeks compared to 18.9% of patients receiving placebo 1, 2
• If a patient has not lost 5% of their total body weight after 12 weeks on the maintenance dose, the medication should be discontinued as they are likely a poor responder 1

Dosing and Administration

• Available in tablets containing 8 mg of naltrexone and 90 mg of bupropion in a sustained-release formulation 1
• Recommended titration schedule:
  • Week 1: 1 tablet daily in the morning
  • Week 2: 1 tablet twice per day
  • Week 3: 2 tablets in morning, 1 in afternoon
  • Week 4 and beyond: 2 tablets twice per day (maintenance dose) 1
• The second dose should not be taken late in the day to minimize insomnia risk 1
• Dose adjustments are required for patients with renal or hepatic impairment:
  • Moderate to severe renal impairment: Total daily dose reduced by half (1 tablet twice daily)
  • End-stage renal disease: Avoid use
  • Moderate to severe hepatic impairment: Maximum 1 tablet daily 1

Side Effects and Safety Considerations

• Most common side effects include nausea, constipation, headache, dizziness, insomnia, dry mouth, and vomiting 1, 2
• Serious but rare adverse effects may include:
  • Suicidal thoughts (bupropion carries a black box warning related to increased suicidal thoughts in young adults) 1, 3
  • Seizures (bupropion may lower seizure threshold) 1, 3
• Vital signs should be monitored as the combination can cause a small increase in heart rate and should be avoided in patients with uncontrolled hypertension 1, 2
• Due to the opioid antagonism from naltrexone, it should not be used in patients requiring opioid therapy 1
• Should be discontinued before procedures requiring opiates (e.g., endoscopies using fentanyl) 1
• Should be avoided in patients with epilepsy or history of seizures 1
• Contraindicated in patients taking monoamine oxidase inhibitors or within 14 days of discontinuing them 1

Ideal Candidates

• Patients who describe food cravings or addictive behaviors related to food 1, 4
• Patients with concomitant depression who may benefit from the bupropion component 1
• Patients attempting to quit smoking or reduce alcohol intake 1
• Patients with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity 1

Contraindications and Poor Candidates

• Patients requiring opioid therapy 1
• Patients with uncontrolled hypertension 1
• Patients with a history of seizures or conditions that predispose to seizures 1
• Patients with anorexia or bulimia nervosa 1
• Patients who have recently discontinued alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
• Patients with end-stage renal disease 1