Drug interactions
Fluoxetine + Maprotiline
Severity: Major
Fluoxetine and Maprotiline: major interaction.
Last updated Sources: US FDA label
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
Fluoxetine strongly inhibits CYP2D6 and can substantially raise maprotiline concentrations, increasing the risk of seizures, cardiac conduction effects and anticholinergic toxicity. The combination also adds serotonergic effects with a risk of serotonin syndrome.
What this interaction means in plain words
Fluoxetine and Maprotiline can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Fluoxetine belongs to Central Nervous System; Maprotiline belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by fluoxetine and norfluoxetine reduces maprotiline clearance, plus additive serotonergic activity.
What to do
Avoid if possible. If combined, start maprotiline at a reduced dose, monitor levels, ECG and serotonin toxicity signs, and remember that fluoxetine's effect persists for weeks after stopping.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Maprotiline
- Arsenic trioxide + Maprotiline Contraindicated
- Disopyramide + Maprotiline Contraindicated
- Dofetilide + Maprotiline Contraindicated
- Ibutilide + Maprotiline Contraindicated
- Isocarboxazid + Maprotiline Contraindicated
- Maprotiline + Methylene blue Contraindicated
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 Maprotiline?
MediHelp rates the interaction as major. Fluoxetine and Maprotiline can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Fluoxetine strongly inhibits CYP2D6 and can substantially raise maprotiline concentrations, increasing the risk of seizures, cardiac conduction effects and anticholinergic toxicity. The combination also adds serotonergic effects with a risk of serotonin syndrome.
How serious is the interaction between Fluoxetine and Maprotiline?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid if possible. If combined, start maprotiline at a reduced dose, monitor levels, ECG and serotonin toxicity signs, and remember that fluoxetine's effect persists for weeks after stopping.
What other medicines interact with Maprotiline?
MediHelp also lists interactions of Maprotiline with, for example, Arsenic trioxide, Disopyramide, Dofetilide. The full list is on the Maprotiline page.
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