Drug interactions
Diphenhydramine + Protriptyline
Severity: Moderate
Diphenhydramine and Protriptyline: 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
Protriptyline is a tricyclic antidepressant with antimuscarinic effects, and combining it with diphenhydramine increases anticholinergic burden, causing dry mouth, urinary retention, constipation, tachycardia and delirium. Additive sedation may also occur, although protriptyline is less sedating than other tricyclics. Diphenhydramine also inhibits CYP2D6, which may raise tricyclic concentrations.
What this interaction means in plain words
Diphenhydramine and Protriptyline 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.
Why it happens
Additive muscarinic blockade and CNS depression, with possible CYP2D6 inhibition by diphenhydramine.
What to do
Avoid regular combined use and choose a non-anticholinergic antihistamine. Monitor for anticholinergic toxicity, especially in older patients or those with glaucoma or urinary retention.
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
Frequently asked questions
Can I take Diphenhydramine with Protriptyline?
MediHelp rates the interaction as moderate. Diphenhydramine and Protriptyline 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. Protriptyline is a tricyclic antidepressant with antimuscarinic effects, and combining it with diphenhydramine increases anticholinergic burden, causing dry mouth, urinary retention, constipation, tachycardia and delirium. Additive sedation may also occur, although protriptyline is less sedating than other tricyclics. Diphenhydramine also inhibits CYP2D6, which may raise tricyclic concentrations.
How serious is the interaction between Diphenhydramine and Protriptyline?
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 regular combined use and choose a non-anticholinergic antihistamine. Monitor for anticholinergic toxicity, especially in older patients or those with glaucoma or urinary retention.
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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