Drug interactions
Donepezil + Paroxetine
Severity: Moderate
Donepezil and Paroxetine: 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
Paroxetine inhibits CYP2D6, which partly metabolizes donepezil, so donepezil levels may increase modestly. Donepezil can also prolong QT and cause bradycardia, so cholinergic adverse effects and arrhythmia risk may increase.
What this interaction means in plain words
Donepezil and Paroxetine 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; Paroxetine belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by paroxetine reduces donepezil clearance, plus additive QT effects.
What to do
Monitor for bradycardia, syncope, nausea and diarrhea, and consider an ECG in patients with cardiac risk. Reduce the donepezil dose if cholinergic effects appear.
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 Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline 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 Paroxetine?
MediHelp rates the interaction as moderate. Donepezil and Paroxetine 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. Paroxetine inhibits CYP2D6, which partly metabolizes donepezil, so donepezil levels may increase modestly. Donepezil can also prolong QT and cause bradycardia, so cholinergic adverse effects and arrhythmia risk may increase.
How serious is the interaction between Donepezil and Paroxetine?
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 bradycardia, syncope, nausea and diarrhea, and consider an ECG in patients with cardiac risk. Reduce the donepezil dose if cholinergic effects appear.
What other medicines interact with Paroxetine?
MediHelp also lists interactions of Paroxetine with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Paroxetine page.
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