Drug interactions
Donepezil + Fluoxetine
Severity: Moderate
Donepezil and Fluoxetine: 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
Fluoxetine inhibits CYP2D6, which can raise donepezil concentrations, and both drugs can prolong the QT interval. Donepezil also causes bradycardia, so the combination may raise the risk of arrhythmia, syncope and cholinergic adverse effects.
What this interaction means in plain words
Donepezil and Fluoxetine 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.
Donepezil belongs to Central Nervous System; Fluoxetine belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by fluoxetine reduces donepezil clearance, plus additive QT prolongation.
What to do
Monitor heart rate and watch for bradycardia, syncope, nausea and other cholinergic effects, with ECG monitoring in patients with cardiac risk factors. Reduce the donepezil dose if adverse effects emerge.
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 Fluoxetine
- Fluoxetine + Isocarboxazid Contraindicated
- Fluoxetine + Mavacamten Contraindicated
- Fluoxetine + Methylene blue Contraindicated
- Fluoxetine + Phenelzine Contraindicated
- Fluoxetine + Pimozide Contraindicated
- Fluoxetine + Rasagiline Contraindicated
Other interactions of Donepezil
- Donepezil + Dronedarone Contraindicated
- Donepezil + Pimozide Contraindicated
- Donepezil + Thioridazine Contraindicated
- Donepezil + Vandetanib Contraindicated
- Amiodarone + Donepezil Major
- Amisulpride + Donepezil Major
Frequently asked questions
Can I take Donepezil with Fluoxetine?
MediHelp rates the interaction as moderate. Donepezil and Fluoxetine 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 inhibits CYP2D6, which can raise donepezil concentrations, and both drugs can prolong the QT interval. Donepezil also causes bradycardia, so the combination may raise the risk of arrhythmia, syncope and cholinergic adverse effects.
How serious is the interaction between Donepezil and Fluoxetine?
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 heart rate and watch for bradycardia, syncope, nausea and other cholinergic effects, with ECG monitoring in patients with cardiac risk factors. Reduce the donepezil dose if adverse effects emerge.
What other medicines interact with Fluoxetine?
MediHelp also lists interactions of Fluoxetine with, for example, Isocarboxazid, Mavacamten, Methylene blue. The full list is on the Fluoxetine page.
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