Drug interactions
Clozapine + Diphenhydramine
Severity: Moderate
Clozapine and Diphenhydramine: 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 adds sedative and anticholinergic effects to those of clozapine, increasing the risk of drowsiness, confusion, constipation, urinary retention and tachycardia. Severe constipation or ileus is a particular concern with clozapine.
What this interaction means in plain words
Clozapine and Diphenhydramine 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.
Clozapine belongs to Central Nervous System; Diphenhydramine belongs to Respiratory.
Why it happens
Additive antihistaminic sedation and antimuscarinic activity.
What to do
Monitor sedation and bowel function, and avoid regular or high-dose diphenhydramine. Use a non-sedating 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 Clozapine
- Clozapine + Deferiprone Contraindicated
- Clozapine + Irinotecan Contraindicated
- Clozapine + Pimozide Contraindicated
- Clozapine + Thioridazine Contraindicated
- Acalabrutinib + Clozapine Major
- Adagrasib + Clozapine Major
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Clozapine with Diphenhydramine?
MediHelp rates the interaction as moderate. Clozapine and Diphenhydramine 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 adds sedative and anticholinergic effects to those of clozapine, increasing the risk of drowsiness, confusion, constipation, urinary retention and tachycardia. Severe constipation or ileus is a particular concern with clozapine.
How serious is the interaction between Clozapine and Diphenhydramine?
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 sedation and bowel function, and avoid regular or high-dose diphenhydramine. Use a non-sedating antihistamine where possible.
What other medicines interact with Clozapine?
MediHelp also lists interactions of Clozapine with, for example, Deferiprone, Irinotecan, Pimozide. The full list is on the Clozapine page.
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