Drug interactions
Donepezil + Phenytoin
Severity: Moderate
Donepezil and Phenytoin: 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
Phenytoin is an inducer of CYP3A4 and can lower donepezil plasma levels, potentially weakening its benefit. Labeling notes that enzyme inducers may increase the rate of donepezil elimination.
What this interaction means in plain words
Donepezil and Phenytoin 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; Phenytoin belongs to Central Nervous System.
Why it happens
Phenytoin induces CYP3A4 (and other enzymes), increasing donepezil clearance.
What to do
Monitor cognitive response and consider titrating donepezil to effect within the approved range. Reassess if phenytoin is stopped, as donepezil exposure may then rise.
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?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Donepezil and Phenytoin, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 7 days on the web. No card needed.
Other interactions of Donepezil
- Donepezil + Dronedarone Contraindicated
- Donepezil + Pimozide Contraindicated
- Donepezil + Thioridazine Contraindicated
- Donepezil + Vandetanib Contraindicated
- Amiodarone + Donepezil Major
- Amisulpride + Donepezil Major
Other interactions of Phenytoin
- Artemether / lumefantrine + Phenytoin Contraindicated
- Bictegravir + Phenytoin Contraindicated
- Cabotegravir + Phenytoin Contraindicated
- Doravirine + Phenytoin Contraindicated
- Elbasvir / grazoprevir + Phenytoin Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Phenytoin Contraindicated
Frequently asked questions
Can I take Donepezil with Phenytoin?
MediHelp rates the interaction as moderate. Donepezil and Phenytoin 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. Phenytoin is an inducer of CYP3A4 and can lower donepezil plasma levels, potentially weakening its benefit. Labeling notes that enzyme inducers may increase the rate of donepezil elimination.
How serious is the interaction between Donepezil and Phenytoin?
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 cognitive response and consider titrating donepezil to effect within the approved range. Reassess if phenytoin is stopped, as donepezil exposure may then rise.
What other medicines interact with Donepezil?
MediHelp also lists interactions of Donepezil with, for example, Dronedarone, Pimozide, Thioridazine. The full list is on the Donepezil page.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
