Drug interactions
Diphenhydramine + Hydroxyzine
Severity: Moderate
Diphenhydramine and Hydroxyzine: 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
Both are sedating first-generation antihistamines with antimuscarinic activity. Together they increase drowsiness, impair psychomotor performance, and can cause anticholinergic effects such as dry mouth, urinary retention and confusion, particularly in older adults.
What this interaction means in plain words
Diphenhydramine and Hydroxyzine 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; Hydroxyzine belongs to Respiratory.
Why it happens
Additive H1 receptor antagonism and muscarinic blockade with CNS depression.
What to do
Avoid duplicate sedating antihistamine therapy; use only one agent and counsel against driving or alcohol use.
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 Hydroxyzine
- Droperidol + Hydroxyzine Contraindicated
- Hydroxyzine + Pimozide Contraindicated
- Hydroxyzine + Thioridazine Contraindicated
- Hydroxyzine + Vandetanib Contraindicated
- Alfentanil + Hydroxyzine Major
- Amiodarone + Hydroxyzine Major
Frequently asked questions
Can I take Diphenhydramine with Hydroxyzine?
MediHelp rates the interaction as moderate. Diphenhydramine and Hydroxyzine 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. Both are sedating first-generation antihistamines with antimuscarinic activity. Together they increase drowsiness, impair psychomotor performance, and can cause anticholinergic effects such as dry mouth, urinary retention and confusion, particularly in older adults.
How serious is the interaction between Diphenhydramine and Hydroxyzine?
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 duplicate sedating antihistamine therapy; use only one agent and counsel against driving or alcohol use.
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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