Drug interactions
Diphenhydramine + Perphenazine
Severity: Moderate
Diphenhydramine and Perphenazine: 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
Combining a phenothiazine with a sedating antihistamine increases drowsiness and impairs alertness. Additive anticholinergic effects can cause dry mouth, constipation, urinary retention, blurred vision and confusion, particularly in older adults. Diphenhydramine is also commonly used to treat perphenazine-induced extrapyramidal symptoms, so the pairing is often intentional but needs monitoring.
What this interaction means in plain words
Diphenhydramine and Perphenazine 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; Perphenazine belongs to Central Nervous System.
Why it happens
Additive CNS depressant and anticholinergic effects at muscarinic and histamine H1 receptors.
What to do
Monitor for oversedation and anticholinergic toxicity, especially in elderly patients, and use the lowest effective diphenhydramine dose for the shortest time. Reassess the need for the antihistamine regularly.
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 Perphenazine
- Ibutilide + Perphenazine Contraindicated
- Perphenazine + Pimozide Contraindicated
- Perphenazine + Thioridazine Contraindicated
- Adagrasib + Perphenazine Major
- Alfentanil + Perphenazine Major
- Amiodarone + Perphenazine Major
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Perphenazine?
MediHelp rates the interaction as moderate. Diphenhydramine and Perphenazine 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. Combining a phenothiazine with a sedating antihistamine increases drowsiness and impairs alertness. Additive anticholinergic effects can cause dry mouth, constipation, urinary retention, blurred vision and confusion, particularly in older adults. Diphenhydramine is also commonly used to treat perphenazine-induced extrapyramidal symptoms, so the pairing is often intentional but needs monitoring.
How serious is the interaction between Diphenhydramine and Perphenazine?
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 oversedation and anticholinergic toxicity, especially in elderly patients, and use the lowest effective diphenhydramine dose for the shortest time. Reassess the need for the antihistamine regularly.
What other medicines interact with Perphenazine?
MediHelp also lists interactions of Perphenazine with, for example, Ibutilide, Pimozide, Thioridazine. The full list is on the Perphenazine page.
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