Fluoxetine and Mexiletine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fluoxetine
Mexiletine
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 substrate exposure and an increased risk of CYP2D6 substrate-related adverse events
Interaction Deep Dive
Coadministration of FLUoxetine (a strong CYP2D6 inhibitor) with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate Therapy with medications that are predominantly metabolized by the CYP2D6 and that have a relatively narrow therapeutic index should be initiated at the low end of the dose range if a patient is receiving FLUoxetine concurrently or has taken it in the previous 5 weeks. If FLUoxetine is added to the treatment regimen of a patient already receiving a CYP2D6 substrate, the need for decreased dose of the original medication should be considered. Use caution during coadministration1.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated metabolism by FLUoxetine
Common questions
Can I take Fluoxetine and Mexiletine together?
Increased CYP2D6 substrate exposure and an increased risk of CYP2D6 substrate-related adverse events Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fluoxetine and Mexiletine 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Fluoxetine or Mexiletine 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: PROZAC(R) oral capsules, fluoxetine oral capsules. Lilly USA LLC (per FDA), Indianapolis, IN, 2023. DailyMed
Keep reading about Fluoxetine
Keep reading about Mexiletine
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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