Drug interactions
Diphenhydramine + Duloxetine
Severity: Minor
Diphenhydramine and Duloxetine: minor 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, one of the pathways involved in duloxetine metabolism, and may modestly raise duloxetine concentrations. Additive sedation and anticholinergic effects such as dry mouth, constipation and urinary retention may also occur.
What this interaction means in plain words
Diphenhydramine and Duloxetine have a small, usually unimportant interaction. Most people can take both; the pharmacist may still mention it so that any unexpected effect is recognised.
Diphenhydramine belongs to Respiratory; Duloxetine belongs to Central Nervous System.
Why it happens
Diphenhydramine inhibits CYP2D6 metabolism of duloxetine, together with additive CNS and anticholinergic effects.
What to do
Monitor for sedation, urinary retention and duloxetine adverse effects, especially in older adults. Use a non-sedating antihistamine if prolonged therapy is needed.
What to ask your pharmacist
- Is there anything I should notice while taking both?
- Do I need to tell my doctor at the next visit?
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Other interactions of Duloxetine
- Duloxetine + Isocarboxazid Contraindicated
- Duloxetine + Linezolid Contraindicated
- Duloxetine + Methylene blue Contraindicated
- Duloxetine + Phenelzine Contraindicated
- Duloxetine + Procarbazine Contraindicated
- Duloxetine + Rasagiline Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Duloxetine?
MediHelp rates the interaction as minor. Diphenhydramine and Duloxetine have a small, usually unimportant interaction. Most people can take both; the pharmacist may still mention it so that any unexpected effect is recognised. Diphenhydramine inhibits CYP2D6, one of the pathways involved in duloxetine metabolism, and may modestly raise duloxetine concentrations. Additive sedation and anticholinergic effects such as dry mouth, constipation and urinary retention may also occur.
How serious is the interaction between Diphenhydramine and Duloxetine?
MediHelp rates it minor, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for sedation, urinary retention and duloxetine adverse effects, especially in older adults. Use a non-sedating antihistamine if prolonged therapy is needed.
What other medicines interact with Duloxetine?
MediHelp also lists interactions of Duloxetine with, for example, Isocarboxazid, Linezolid, Methylene blue. The full list is on the Duloxetine page.
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