Drug interactions
Diphenhydramine + Primidone
Severity: Moderate
Diphenhydramine and Primidone: 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
Primidone, which is metabolised partly to phenobarbital, causes sedation, and diphenhydramine adds to the depressant effect. Drowsiness, dizziness and impaired coordination may increase.
What this interaction means in plain words
Diphenhydramine and Primidone 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; Primidone belongs to Central Nervous System.
Why it happens
Additive CNS depression from GABAergic barbiturate activity and central H1 antagonism.
What to do
Counsel patients to avoid driving and alcohol, and consider a non-sedating antihistamine. Monitor for excessive sedation, especially in older adults.
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 Diphenhydramine
Other interactions of Primidone
- Lorlatinib + Primidone Contraindicated
- Lurasidone + Primidone Contraindicated
- Primidone + Ranolazine Contraindicated
- Primidone + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
- Primidone + Voriconazole Contraindicated
- Abiraterone + Primidone Major
Frequently asked questions
Can I take Diphenhydramine with Primidone?
MediHelp rates the interaction as moderate. Diphenhydramine and Primidone 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. Primidone, which is metabolised partly to phenobarbital, causes sedation, and diphenhydramine adds to the depressant effect. Drowsiness, dizziness and impaired coordination may increase.
How serious is the interaction between Diphenhydramine and Primidone?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Counsel patients to avoid driving and alcohol, and consider a non-sedating antihistamine. Monitor for excessive sedation, especially in older adults.
What other medicines interact with Diphenhydramine?
MediHelp also lists interactions of Diphenhydramine with, for example, Alfentanil, Belladonna and opium, Benzhydrocodone / acetaminophen. The full list is on the Diphenhydramine page.
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