Maprotiline and Ranolazine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ranolazine
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 CYP2D6 substrates exposure
Interaction Deep Dive
Coadministration of ranolazine and CYP2D6 substrates may increase CYP2D6 substrates exposure. Hence, lower doses of these substrates may be required. In a drug interaction study, coadministration of ranolazine 750 mg twice daily with a single dose of immediate release metoprolol (100 mg), a CYP2D6 substrate resulted in increased metoprolol exposure by 80% in extensive CYP2D6 metabolizers with no need for dose adjustment of metoprolol. In extensive metabolizers of dextromethorphan, a substrate of CYP2D6, ranolazine inhibits partially the formation of the main metabolite dextrorphan1.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated metabolism by ranolazine
Literature reports
1 report — tap to read
a) In a drug interaction study, coadministration of ranolazine 750 mg twice daily with a single dose of immediate release metoprolol (100 mg), a CYP2D6 substrate resulted in increased metoprolol exposure by 80% in extensive CYP2D6 metabolizers with no need for dose adjustment of metoprolol. In extensive metabolizers of dextromethorphan, a substrate of CYP2D6, ranolazine inhibits partially the formation of the main metabolite dextrorphan 1.
Common questions
Can I take Maprotiline and Ranolazine together?
Increased CYP2D6 substrates exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Maprotiline and Ranolazine 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 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 Maprotiline or Ranolazine 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: RANOLAZINE oral extended-release tablets, ranolazine oral extended-release tablets. Viona Pharmaceuticals Inc. (per Dailymed), Cranford, NJ, 2023. DailyMed
Keep reading about Ranolazine
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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