Drug interactions
Diphenhydramine + Perhexiline
Severity: Moderate
Diphenhydramine and Perhexiline: 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 inhibits CYP2D6, the main enzyme clearing perhexiline, which could raise perhexiline concentrations. Perhexiline has a narrow therapeutic window, with hepatotoxicity and neurotoxicity at high levels, so even modest rises may matter.
What this interaction means in plain words
Diphenhydramine and Perhexiline 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.
Why it happens
Diphenhydramine inhibits CYP2D6-mediated metabolism of perhexiline, reducing its clearance.
What to do
Monitor perhexiline plasma concentrations and liver function if diphenhydramine is used regularly. Prefer a non-CYP2D6-inhibiting antihistamine where possible.
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
Frequently asked questions
Can I take Diphenhydramine with Perhexiline?
MediHelp rates the interaction as moderate. Diphenhydramine and Perhexiline 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 inhibits CYP2D6, the main enzyme clearing perhexiline, which could raise perhexiline concentrations. Perhexiline has a narrow therapeutic window, with hepatotoxicity and neurotoxicity at high levels, so even modest rises may matter.
How serious is the interaction between Diphenhydramine and Perhexiline?
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 perhexiline plasma concentrations and liver function if diphenhydramine is used regularly. Prefer a non-CYP2D6-inhibiting antihistamine where possible.
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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