Drug interactions
Diphenhydramine + Doxepin
Severity: Moderate
Diphenhydramine and Doxepin: 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 drugs are sedating and strongly anticholinergic, so combining them produces additive drowsiness, confusion, dry mouth, constipation, urinary retention and blurred vision. Older adults are at particular risk of delirium and falls.
What this interaction means in plain words
Diphenhydramine and Doxepin 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; Doxepin belongs to Dermatology.
Why it happens
Additive H1-receptor antagonism and muscarinic receptor blockade, producing combined CNS depression and anticholinergic effects.
What to do
Avoid combining in older patients and limit to the lowest effective doses in others. Monitor for oversedation and anticholinergic toxicity such as urinary retention and confusion.
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 Doxepin
- Doxepin + Isocarboxazid Contraindicated
- Doxepin + Phenelzine Contraindicated
- Doxepin + Procarbazine Contraindicated
- Doxepin + Safinamide Contraindicated
- Doxepin + Selegiline Contraindicated
- Doxepin + Tranylcypromine Contraindicated
Frequently asked questions
Can I take Diphenhydramine with Doxepin?
MediHelp rates the interaction as moderate. Diphenhydramine and Doxepin 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 drugs are sedating and strongly anticholinergic, so combining them produces additive drowsiness, confusion, dry mouth, constipation, urinary retention and blurred vision. Older adults are at particular risk of delirium and falls.
How serious is the interaction between Diphenhydramine and Doxepin?
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 combining in older patients and limit to the lowest effective doses in others. Monitor for oversedation and anticholinergic toxicity such as urinary retention and confusion.
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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