Buprenorphine and Isocarboxazid: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
Isocarboxazid
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
These two medicines should not be taken together. Buprenorphine (like Belbuca, Butrans, or Sublocade) is an opioid, and isocarboxazid (Marplan) is an older type of antidepressant called an MAO inhibitor. When they are combined, they can each slow down your brain and nervous system, and together that effect can add up.
This could make you very sleepy, slow your breathing, lower your blood pressure, or make you confused. The good news is this is preventable. If you have been prescribed both, do not stop either one on your own. Instead, reach out to your pharmacist or doctor right away so they can choose a safer plan for you.
Combination is contraindicated. Buprenorphine (a partial mu-opioid agonist) plus isocarboxazid (a nonselective MAO inhibitor) carries risk of additive CNS and respiratory depression, and MAOIs may potentiate opioid effects.
- Mechanism: additive pharmacodynamic CNS depression; neither drug is a prodrug here, so the direction is straightforward potentiation.
- Direction: increased opioid/CNS depressant effect (sedation, hypotension, hypoventilation).
- Evidence: theoretical; onset unspecified.
- Management: avoid concurrent use. If an opioid is required, select an alternative and observe recommended MAOI washout intervals per prescriber guidance, with close CNS and respiratory monitoring.
What happens
An increased risk of CNS depression
Interaction Deep Dive
The combination of isocarboxazid with narcotics is contraindicated owing to their potential for potentiating effects1.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
The main step here is avoidance, since this pairing is contraindicated. Your care team will typically not use these two together and will look for a safer option.
- Keep taking your medicines exactly as prescribed, and do not stop either one on your own.
- Tell your pharmacist or prescriber promptly that both have been ordered so they can choose an alternative or plan appropriate timing between them.
- Watch for and report unusual drowsiness, slowed or shallow breathing, dizziness, or confusion.
Your team can manage this safely by selecting a different pain medicine or adjusting the plan for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Buprenorphine and Isocarboxazid together?
Buprenorphine and isocarboxazid should not be taken together because they can add up to dangerous nervous system and breathing slowdown. Contact your pharmacist or prescriber right away so they can arrange a safer alternative. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Isocarboxazid interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Buprenorphine and Isocarboxazid interaction managed?
The main step here is avoidance, since this pairing is contraindicated. Your care team will typically not use these two together and will look for a safer option. Keep taking your medicines exactly as prescribed, and do not stop either one on your own. Tell your pharmacist or prescriber promptly that both have been ordered so they can choose an alternative or plan appropriate timing between them.… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Buprenorphine or Isocarboxazid need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: MARPLAN oral tablets, isocarboxazid oral tablets. Validus Pharmaceuticals LLC (per Dailymed), Parsippany, NJ, 2023. DailyMed
Keep reading about Buprenorphine
Keep reading about Isocarboxazid
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