Drug interactions
Diphenhydramine + Donepezil
Severity: Moderate
Diphenhydramine and Donepezil: 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
Diphenhydramine is strongly anticholinergic and opposes the cholinergic action of donepezil, potentially reducing its cognitive benefit. Donepezil may also lessen some of diphenhydramine's effects.
What this interaction means in plain words
Diphenhydramine and Donepezil 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.
Diphenhydramine belongs to Respiratory; Donepezil belongs to Central Nervous System.
Why it happens
Pharmacodynamic antagonism between a cholinesterase inhibitor and a muscarinic antagonist.
What to do
Avoid diphenhydramine in patients with dementia taking donepezil and choose a non-sedating, non-anticholinergic antihistamine or other alternative. Monitor cognition if use is unavoidable.
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 Donepezil
- Donepezil + Dronedarone Contraindicated
- Donepezil + Pimozide Contraindicated
- Donepezil + Thioridazine Contraindicated
- Donepezil + Vandetanib Contraindicated
- Amiodarone + Donepezil Major
- Amisulpride + Donepezil Major
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Donepezil?
MediHelp rates the interaction as moderate. Diphenhydramine and Donepezil 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. Diphenhydramine is strongly anticholinergic and opposes the cholinergic action of donepezil, potentially reducing its cognitive benefit. Donepezil may also lessen some of diphenhydramine's effects.
How serious is the interaction between Diphenhydramine and Donepezil?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid diphenhydramine in patients with dementia taking donepezil and choose a non-sedating, non-anticholinergic antihistamine or other alternative. Monitor cognition if use is unavoidable.
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.
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