Drug interactions
Fluoxetine + Mexiletine
Severity: Moderate
Fluoxetine and Mexiletine: moderate interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Mexiletine is partly metabolized by CYP2D6, which fluoxetine strongly inhibits, so mexiletine concentrations may rise. This can increase dose-related adverse effects such as tremor, nausea, dizziness and proarrhythmia.
What this interaction means in plain words
Fluoxetine and Mexiletine can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Fluoxetine belongs to Central Nervous System; Mexiletine belongs to Cardiovascular.
Why it happens
Fluoxetine and its metabolite inhibit CYP2D6, reducing mexiletine clearance.
What to do
Monitor for mexiletine toxicity and ECG changes, and reduce the mexiletine dose if adverse effects appear when fluoxetine is started or stopped.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Mexiletine
- Fezolinetant + Mexiletine Contraindicated
- Mexiletine + Pimozide Contraindicated
- Alosetron + Mexiletine Major
- Amiodarone + Mexiletine Major
- Clozapine + Mexiletine Major
- Cobicistat + Mexiletine Major
Other interactions of Fluoxetine
- Fluoxetine + Isocarboxazid Contraindicated
- Fluoxetine + Mavacamten Contraindicated
- Fluoxetine + Methylene blue Contraindicated
- Fluoxetine + Phenelzine Contraindicated
- Fluoxetine + Pimozide Contraindicated
- Fluoxetine + Rasagiline Contraindicated
Frequently asked questions
Can I take Fluoxetine with Mexiletine?
MediHelp rates the interaction as moderate. Fluoxetine and Mexiletine can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Mexiletine is partly metabolized by CYP2D6, which fluoxetine strongly inhibits, so mexiletine concentrations may rise. This can increase dose-related adverse effects such as tremor, nausea, dizziness and proarrhythmia.
How serious is the interaction between Fluoxetine and Mexiletine?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for mexiletine toxicity and ECG changes, and reduce the mexiletine dose if adverse effects appear when fluoxetine is started or stopped.
What other medicines interact with Mexiletine?
MediHelp also lists interactions of Mexiletine with, for example, Fezolinetant, Pimozide, Alosetron. The full list is on the Mexiletine page.
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