Drug interactions
Diphenhydramine + Imipramine
Severity: Moderate
Diphenhydramine and Imipramine: 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 imipramine's active metabolite desipramine, so tricyclic concentrations may increase. Both drugs are also sedating and strongly anticholinergic, which increases the risk of confusion, urinary retention, constipation and tachycardia.
What this interaction means in plain words
Diphenhydramine and Imipramine 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; Imipramine belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by diphenhydramine plus additive CNS depressant and antimuscarinic effects.
What to do
Limit diphenhydramine use, particularly in older patients, and monitor for sedation, anticholinergic toxicity and tricyclic adverse effects. Consider imipramine dose reduction or 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 Imipramine
- Dronedarone + Imipramine Contraindicated
- Imipramine + Isocarboxazid Contraindicated
- Imipramine + Phenelzine Contraindicated
- Imipramine + Pimozide Contraindicated
- Imipramine + Rasagiline Contraindicated
- Imipramine + Safinamide Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Imipramine?
MediHelp rates the interaction as moderate. Diphenhydramine and Imipramine 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 imipramine's active metabolite desipramine, so tricyclic concentrations may increase. Both drugs are also sedating and strongly anticholinergic, which increases the risk of confusion, urinary retention, constipation and tachycardia.
How serious is the interaction between Diphenhydramine and Imipramine?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Limit diphenhydramine use, particularly in older patients, and monitor for sedation, anticholinergic toxicity and tricyclic adverse effects. Consider imipramine dose reduction or a non-sedating antihistamine.
What other medicines interact with Imipramine?
MediHelp also lists interactions of Imipramine with, for example, Dronedarone, Isocarboxazid, Phenelzine. The full list is on the Imipramine page.
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