Drug interactions
Diphenhydramine + Iloperidone
Severity: Moderate
Diphenhydramine and Iloperidone: 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 and may raise iloperidone exposure, which could increase QT prolongation, orthostatic hypotension and sedation. Both drugs are also sedating and anticholinergic, so additive drowsiness, dizziness and anticholinergic effects can occur.
What this interaction means in plain words
Diphenhydramine and Iloperidone 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; Iloperidone belongs to Central Nervous System.
Why it happens
Diphenhydramine inhibits CYP2D6-mediated iloperidone metabolism, plus additive CNS depressant and anticholinergic effects.
What to do
Monitor for sedation, orthostatic hypotension and anticholinergic effects, and consider ECG monitoring if other QT-prolonging risks exist. Limit diphenhydramine use to short courses or use a non-sedating antihistamine.
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 Iloperidone
- Iloperidone + Thioridazine Contraindicated
- Alfuzosin + Iloperidone Major
- Amiodarone + Iloperidone Major
- Amisulpride + Iloperidone Major
- Amitriptyline + Iloperidone Major
- Anagrelide + Iloperidone Major
Frequently asked questions
Can I take Diphenhydramine with Iloperidone?
MediHelp rates the interaction as moderate. Diphenhydramine and Iloperidone 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 and may raise iloperidone exposure, which could increase QT prolongation, orthostatic hypotension and sedation. Both drugs are also sedating and anticholinergic, so additive drowsiness, dizziness and anticholinergic effects can occur.
How serious is the interaction between Diphenhydramine and Iloperidone?
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 sedation, orthostatic hypotension and anticholinergic effects, and consider ECG monitoring if other QT-prolonging risks exist. Limit diphenhydramine use to short courses or use a non-sedating antihistamine.
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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