Is Contrave (naltrexone-bupropion) safe to use with Viagra (sildenafil)?

Safety of Contrave (Naltrexone-Bupropion) with Viagra (Sildenafil)

Contrave can be safely used with Viagra (sildenafil) as there are no significant drug interactions between these medications that would increase risk of adverse cardiovascular events.

Pharmacological Considerations

Mechanism of Action

• Contrave (naltrexone-bupropion): Works through two mechanisms:
  • Bupropion stimulates hypothalamic proopiomelanocortin neurons
  • Naltrexone blocks opioid-mediated proopiomelanocortin autoinhibition 1
• Viagra (sildenafil): Acts as a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE-5), resulting in smooth muscle relaxation and vasodilation 2

Metabolism and Interactions

• Bupropion is predominantly metabolized by the P450 2B6 pathway 3
• Sildenafil is metabolized by both P450 2C9 and P450 3A4 pathways 2
• There is no direct metabolic interaction between these medications that would cause concerning drug-drug interactions

Safety Profile

Cardiovascular Considerations

• Unlike nitrates, which are absolutely contraindicated with sildenafil due to potentially life-threatening hypotension, Contrave does not have this interaction 4
• A systematic literature review found no increased risk of major adverse cardiovascular events (MACE) among users of naltrexone/bupropion ER compared with nonusers 5
• Sildenafil's blood pressure-lowering effects are moderate (typically <10% decreases in systolic and diastolic blood pressures) in healthy males 2
• The combination of antihypertensive medications with sildenafil may lead to additive but not potentiating blood pressure decreases, which is generally clinically manageable 6

Monitoring Recommendations

• Blood pressure should be monitored regularly, especially during the first 8 weeks of Contrave treatment, as it can cause modest increases in blood pressure 3
• If a patient experiences significant hypotension when using both medications, consider:
  • Fluid resuscitation as first-line management
  • Temporary dose adjustment of either medication
  • Evaluation for other contributing factors

Precautions and Contraindications

Absolute Contraindications

• Neither medication should be used with:
  • Monoamine oxidase inhibitors (MAOIs) 3
  • Organic nitrates (e.g., nitroglycerin, isosorbide dinitrate) 1, 4

Relative Contraindications/Cautions

• Use with caution in patients with:
  • Uncontrolled hypertension 3, 4
  • Recent myocardial infarction or stroke (within 6 months) 4
  • Unstable angina 4
  • Severe hepatic or renal impairment (may require dose adjustments) 3

Clinical Decision Algorithm

1. Assess baseline cardiovascular risk:

   • If patient has unstable cardiovascular disease, avoid combination
   • If patient is on nitrates, absolutely contraindicated

2. Check for drug interactions:

   • Ensure patient is not on MAOIs or nitrates
   • Review other medications that might affect cytochrome P450 pathways

3. Monitor after initiation:

   • Check blood pressure within 1-2 weeks of starting combination
   • Educate patient about potential symptoms of hypotension (dizziness, lightheadedness)
   • Advise patient to separate timing of medications if possible

4. Adjust as needed:

   • Consider lower starting doses of either medication
   • Discontinue if significant adverse effects occur

Common Side Effects to Monitor

• Headache (common with both medications)
• Flushing (common with sildenafil)
• Nausea (common with Contrave)
• Dizziness (possible with both)
• Blood pressure changes

While both medications individually can affect blood pressure, there is no evidence suggesting a dangerous interaction between Contrave and Viagra that would preclude their combined use in appropriate patients without specific contraindications.