Maprotiline and Safinamide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Safinamide
Maprotiline
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.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Concomitant use of safinamide (an MAO type B inhibitor) and an a tetracyclic antidepressant is contraindicated due to the potential of life-threatening serotonin syndrome, which has been reported. Wait at least 14 days after discontinuation of safinamide before initiating a tetracyclic antidepressant1.
Why it happens (mechanism)
Additive serotonergic effects
Literature reports
1 report — tap to read
a) Cases of serotonin syndrome have been reported with the concomitant use of a MAOI (including selective MAOI type B) and a tetracyclic antidepressant 1.
Common questions
Can I take Maprotiline and Safinamide together?
Increased risk of serotonin syndrome Always confirm with your pharmacist or prescriber before making any change.
How serious is the Maprotiline 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 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 Maprotiline 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 Safinamide
Keep reading about Maprotiline
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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