Buprenorphine and Tranylcypromine: 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
Tranylcypromine
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. Tranylcypromine (Parnate) is an older type of antidepressant called an MAO inhibitor. Buprenorphine is a strong opioid pain and addiction medicine that also affects serotonin, a brain chemical. Using them at the same time can cause a dangerous buildup of serotonin (called serotonin syndrome) with symptoms like fever, sweating, shaking, a fast heartbeat, and confusion. The combination can also make you overly sleepy and slow your breathing.
The good news is this is very avoidable. Please talk with your pharmacist or doctor before starting either drug. Your care team can space these out safely or choose a different medicine so you stay protected.
Contraindicated combination. Concurrent buprenorphine (a serotonergic opioid CNS depressant) and tranylcypromine (an irreversible MAOI) poses additive serotonergic risk (serotonin syndrome) plus additive CNS/respiratory depression and opioid-related toxicity. Mechanism is pharmacodynamic, not a prodrug or PK issue.
- Direction: additive/synergistic effects; both agents increase risk.
- Evidence: theoretical, but severity warrants strict avoidance.
- Onset: unspecified.
- Management: Avoid co-administration. Do not start buprenorphine within 14 days of an MAOI. Before initiating tranylcypromine, discontinue the serotonergic agent and wait at least 1 week or 4 to 5 half-lives (whichever is longer). MAO inhibition may persist up to 10 days after tranylcypromine discontinuation.
What happens
An increased risk of serotonin syndrome or opioid-related toxicity and an increased risk of CNS depression
Interaction Deep Dive
Taking tranylcypromine together with buprenorphine (a serotonergic CNS depressant) is contraindicated because the combination can produce severe or life-threatening effects such as serotonin syndrome, along with a heightened risk of CNS depression. Before starting tranylcypromine, stop the serotonergic agent and allow a minimum of 1 week or 4 to 5 half-lives of that agent to elapse, whichever period is longer. The risk of interaction does not end when tranylcypromine is stopped; it continues until MAO activity has recovered adequately. MAO inhibition can last for as long as 10 days after the drug is discontinued3. Because of the increased likelihood of serotonin syndrome and opioid-related toxicity, buprenorphine and tranylcypromine (an MAOI) should not be used together, nor should buprenorphine be given within 14 days of MAOI use 241.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS depression
How to manage this interaction
This pairing is one to avoid, and your care team can manage it safely. Keep taking what you have been prescribed and do not stop anything on your own, but raise this combination right away with your pharmacist or prescriber.
- Your team will usually separate these drugs in time rather than use them together.
- Buprenorphine is generally not started within 14 days of an MAOI like tranylcypromine.
- Before starting tranylcypromine, the other serotonergic drug is stopped and a washout of at least 1 week (or 4 to 5 half-lives, whichever is longer) is allowed.
- MAO effects can linger up to 10 days after stopping tranylcypromine.
Tell your team promptly if you notice fever, agitation, shaking, sweating, a racing heart, or unusual drowsiness.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Buprenorphine and Tranylcypromine together?
Buprenorphine and tranylcypromine should not be used together because of the risk of serotonin syndrome and dangerous sedation; your care team will separate them in time or pick an alternative, so check with your pharmacist or doctor before starting either. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Tranylcypromine 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 Tranylcypromine interaction managed?
This pairing is one to avoid, and your care team can manage it safely. Keep taking what you have been prescribed and do not stop anything on your own, but raise this combination right away with your pharmacist or prescriber. Your team will usually separate these drugs in time rather than use them together. Buprenorphine is generally not started within 14 days of an MAOI like tranylcypromine. Befor… 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 Tranylcypromine 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 (4)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: BUTRANS(R) transdermal system patch, buprenorphine transdermal system patch. Purdue Pharma L.P. (per FDA), Stamford, CT, 2016. DailyMed
- Product Information: Tranylcypromine oral tablets, tranylcypromine oral tablets. Solco Healthcare US, LLC (per DailyMed), Somerset, NJ, 2024. DailyMed
- Product Information: SUBOXONE(R) sublingual film, buprenorphine naloxone sublingual film. Indivior Inc (per FDA), Richmond, VA, 2017. DailyMed
Keep reading about Buprenorphine
Keep reading about Tranylcypromine
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