Drug interactions
Diphenhydramine + Promethazine
Severity: Moderate
Diphenhydramine and Promethazine: 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 strong anticholinergic activity, so the combination duplicates therapy. It increases the risk of marked drowsiness, confusion, urinary retention, constipation and tachycardia, especially in older adults.
What this interaction means in plain words
Diphenhydramine and Promethazine 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; Promethazine belongs to Respiratory.
Why it happens
Additive H1 receptor antagonism and muscarinic blockade.
What to do
Avoid using both together; select a single agent. If combined, use minimal doses and monitor for sedation and anticholinergic toxicity.
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 Promethazine
- Cabergoline + Promethazine Contraindicated
- Dopamine + Promethazine Contraindicated
- Ibutilide + Promethazine Contraindicated
- Pimozide + Promethazine Contraindicated
- Promethazine + Thioridazine Contraindicated
- Alfentanil + Promethazine Major
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Promethazine?
MediHelp rates the interaction as moderate. Diphenhydramine and Promethazine 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 strong anticholinergic activity, so the combination duplicates therapy. It increases the risk of marked drowsiness, confusion, urinary retention, constipation and tachycardia, especially in older adults.
How serious is the interaction between Diphenhydramine and Promethazine?
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 using both together; select a single agent. If combined, use minimal doses and monitor for sedation and anticholinergic toxicity.
What other medicines interact with Promethazine?
MediHelp also lists interactions of Promethazine with, for example, Cabergoline, Dopamine, Ibutilide. The full list is on the Promethazine page.
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