Ozanimod and Amitriptyline: 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
Amitriptyline
Ozanimod
No brand names on record
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 can add up in ways that need attention. Amitriptyline (Elavil) raises brain chemicals like norepinephrine and serotonin. Ozanimod has an active breakdown product that blocks an enzyme called MAO-B. Together, in theory, these could push those chemicals too high and cause serious reactions.
On top of that, ozanimod can briefly slow your heart rate, and amitriptyline can affect your heart's rhythm too, so the two may add together. This is based on lab-level evidence, not proven cases, but because the heart is involved your care team takes it seriously. Please don't stop either drug on your own talk with your doctor or pharmacist, who can plan this safely.
Direction: additive/pharmacodynamic risk, not a straightforward metabolic clearance change. An active ozanimod metabolite inhibits MAO-B in vitro, creating theoretical potential for excess noradrenergic/serotonergic activity when combined with a TCA like amitriptyline.
Cardiac: ozanimod causes transient bradycardia and AV conduction delay on initiation; amitriptyline has QT-prolonging, arrhythmogenic potential, so effects on heart rate/conduction may be additive.
- Evidence: theoretical.
- Severity: major.
- Management: generally avoid initiating ozanimod in patients on QT-prolonging arrhythmogenic drugs; if unavoidable, obtain cardiology input. Monitor HR/rhythm and for serotonergic/adrenergic excess.
What happens
Increased risk of serious adverse reactions and additive effects on heart rate
Interaction Deep Dive
In vitro, an active metabolite of ozanimod inhibits MAO-B, which creates the possibility of serious adverse reactions when ozanimod is given together with agents capable of raising norepinephrine or serotonin (for example, TCAs). Ozanimod can also cause a transient reduction in heart rate along with delays in atrioventricular conduction. Its use has not been evaluated in patients receiving QT-prolonging medications. Because of the risk of additive effects on heart rate, ozanimod therapy should as a rule not be started in patients being treated at the same time with QT prolonging drugs that have recognized arrhythmogenic properties. If such concurrent use cannot be avoided, seek advice from a cardiologist1.
Why it happens (mechanism)
MAO-B inhibition; additive effects on heart rate
How to manage this interaction
The good news: your care team can manage this. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Because ozanimod can slow the heart and amitriptyline can affect heart rhythm, your team may check your heart rate and rhythm, especially when ozanimod is first started.
- In many cases the team prefers not to start ozanimod while you are on a QT-affecting drug like amitriptyline; if using both cannot be avoided, they will usually involve a cardiologist.
- Tell your doctor about any dizziness, fainting, palpitations, fast heartbeat, or a very high fever with agitation.
Raise this combination with your pharmacist or prescriber so they can tailor and monitor it for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Ozanimod and Amitriptyline together?
Combining amitriptyline with ozanimod carries a theoretical risk of serious reactions and additive effects on heart rate and rhythm, so let your care team decide and monitor. Keep taking both as prescribed and report any fainting, palpitations, or feeling very unwell. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ozanimod and Amitriptyline interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Ozanimod and Amitriptyline interaction managed?
The good news: your care team can manage this. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Because ozanimod can slow the heart and amitriptyline can affect heart rhythm, your team may check your heart rate and rhythm, especially when ozanimod is first started. In many cases the team prefers not to start ozanimod while you are on a QT-affecting drug… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Ozanimod or Amitriptyline 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: ZEPOSIA(R) oral capsules, ozanimod oral capsules. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2024. DailyMed
Keep reading about Amitriptyline
Keep reading about Ozanimod
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