Buprenorphine and Safinamide: 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
Safinamide
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.
Taking these two together is not recommended. Safinamide (Xadago) is a Parkinson's medicine that belongs to a group called MAO inhibitors. Buprenorphine is an opioid pain and addiction medicine. When they are combined, both can raise serotonin, a chemical in your body. Too much serotonin can cause a serious problem called serotonin syndrome.
Warning signs include agitation, a fast heartbeat, sweating, shaking, muscle stiffness, and confusion. This can be dangerous, so this combination is one doctors avoid. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor, who can pick a safer plan for you.
Contraindicated combination. Safinamide is a selective MAO-B inhibitor; buprenorphine is a partial opioid agonist with serotonergic activity. Concurrent use produces additive serotonergic effects, creating risk of life-threatening serotonin syndrome (reported, evidence graded probable).
- Direction: additive/pharmacodynamic, not a prodrug or CYP-based interaction.
- Management: avoid coadministration. Allow at least 14 days after discontinuing safinamide before initiating an opioid.
- Monitor for: autonomic instability (tachycardia, hyperthermia, diaphoresis), neuromuscular signs (clonus, hyperreflexia, rigidity), and altered mental status.
Choose a non-serotonergic analgesic alternative in consultation with the prescriber.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
The combined use of an opioid with safinamide, which functions as an MAO type B inhibitor, is contraindicated because of the risk of serotonin syndrome, a condition that can be life-threatening and has been documented. A minimum of 14 days should elapse following the cessation of safinamide before an opioid is started1.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Because this combination can trigger serotonin syndrome, care teams generally avoid using them together.
- If safinamide is being stopped, the guidance is to wait at least 14 days before starting an opioid like buprenorphine.
- Your team may choose a different, non-serotonergic pain option instead.
What you should do: Keep taking your medicines as prescribed and do not stop either one on your own. Tell your pharmacist or prescriber that you have been prescribed both, and get urgent help for symptoms like agitation, fast heartbeat, sweating, shaking, muscle stiffness, or confusion.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Instances of serotonin syndrome have been documented when a MAOI (including selective MAOI type B) is used together with opioids 1.
Common questions
Can I take Buprenorphine and Safinamide together?
Buprenorphine and safinamide should not be used together because of the risk of life-threatening serotonin syndrome; allow at least 14 days after stopping safinamide before starting an opioid, and let your care team choose a safer plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Safinamide 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 Safinamide interaction managed?
Because this combination can trigger serotonin syndrome, care teams generally avoid using them together. If safinamide is being stopped, the guidance is to wait at least 14 days before starting an opioid like buprenorphine. Your team may choose a different, non-serotonergic pain option instead. What you should do: Keep taking your medicines as prescribed and do not stop either one on your own. Tel… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Buprenorphine or Safinamide 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: XADAGO(R) oral tablets, safinamide oral tablets. US WorldMeds, LLC (per FDA), Louisville, KY, 2017. DailyMed
Keep reading about Buprenorphine
Keep reading about Safinamide
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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