Contrave Drug Interactions and Contraindications
Contrave (naltrexone/bupropion) is absolutely contraindicated with MAOIs and opioid medications, requires dose reduction with CYP2B6 inhibitors, and must be used with extreme caution in patients taking drugs that lower seizure threshold or are metabolized by CYP2D6. 1
Absolute Contraindications
MAOIs (Monoamine Oxidase Inhibitors)
- Never use concurrently - bupropion inhibits dopamine/norepinephrine reuptake, creating dangerous hypertensive crisis risk when combined with MAOIs
- Require 14-day washout period both before starting Contrave after stopping an MAOI, and before starting an MAOI after stopping Contrave 1
Opioid Medications
- Contraindicated with chronic opioid use - naltrexone blocks opioid receptors, rendering pain medications ineffective and potentially precipitating withdrawal
- For intermittent opioid needs: temporarily discontinue Contrave (do not increase opioid dose above standard)
- After chronic opioid cessation: wait 7-10 days before restarting Contrave to prevent withdrawal precipitation
- This includes all opioid-containing products: analgesics, cough/cold remedies, antidiarrheals 1
Other Bupropion Products
- Absolutely contraindicated - avoid duplicative therapy and increased seizure risk 1
Critical Drug Interactions Requiring Dose Adjustment
CYP2B6 Inhibitors (Ticlopidine, Clopidogrel)
- Limit Contrave to maximum 2 tablets daily (one morning, one evening) when used concomitantly
- These drugs increase bupropion exposure while decreasing active metabolite levels 1
CYP2B6 Inducers (Ritonavir, Lopinavir, Efavirenz)
- Avoid concomitant use - these dramatically reduce bupropion and metabolite exposure (up to 66% reduction in AUC), potentially eliminating efficacy 1
Major Drug Interactions Requiring Caution
CYP2D6 Substrates
Contrave increases exposure of CYP2D6-metabolized drugs by 2-4 fold. Start these medications at the lower end of dosing range and monitor closely 1:
- Antidepressants: SSRIs, tricyclics (desipramine, venlafaxine)
- Antipsychotics: haloperidol, risperidone, thioridazine
- Beta-blockers: metoprolol (4-fold AUC increase documented)
- Antiarrhythmics: propafenone, flecainide (narrow therapeutic index - particularly dangerous)
Drugs That Lower Seizure Threshold
Use extreme caution with gradual dose titration 1:
- Antipsychotics
- Antidepressants
- Theophylline
- Systemic corticosteroids
Dopaminergic Drugs (Levodopa, Amantadine)
- Monitor for CNS toxicity: restlessness, agitation, tremor, ataxia, gait disturbance, vertigo
- Results from cumulative dopamine agonist effects 1
Digoxin
- Monitor digoxin levels - Contrave may decrease plasma concentrations 1
Clinical Considerations from Guidelines
Seizure Risk Population
Avoid Contrave entirely in patients with seizure disorders and use with extreme caution in those at risk for seizures 2. The 2022 AGA guidelines specifically note this as a key implementation consideration.
Cardiovascular Monitoring
Monitor blood pressure and heart rate periodically, especially during the first 12 weeks of treatment 2. This is critical as the medication can increase both parameters.
Alcohol
Minimize or avoid alcohol consumption - rare reports of neuropsychiatric events and reduced alcohol tolerance with bupropion 1
Additional Practical Considerations
No Dose Adjustment Needed With:
- Atorvastatin, glyburide, lisinopril, nifedipine, valsartan
- Metformin (23% AUC increase but clinically insignificant) 1
Laboratory Interference
- False-positive amphetamine screens can occur with bupropion
- Confirmatory testing (gas chromatography/mass spectrometry) distinguishes bupropion from amphetamines 1
Special Populations
The AGA guidelines note that Contrave may be preferentially considered for patients attempting smoking cessation or those with comorbid depression, given bupropion's established efficacy in these conditions 2.
Common Pitfalls to Avoid
- Don't forget the MAOI washout period - 14 days is mandatory in both directions
- Don't prescribe to patients on chronic opioids without stopping opioids first (7-10 day washout)
- Don't ignore cardiovascular monitoring - BP/HR checks are essential, especially early in treatment
- Don't combine with other bupropion products (Wellbutrin, Zyban, etc.)
- Don't use standard CYP2D6 substrate doses - start low when adding these medications