Drug interactions
Diphenhydramine + Paroxetine
Severity: Minor
Diphenhydramine and Paroxetine: 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 and may modestly raise paroxetine levels, while paroxetine is itself a strong CYP2D6 inhibitor. Both have anticholinergic activity, so additive dry mouth, sedation, confusion and urinary retention may occur, especially in older adults.
What this interaction means in plain words
Diphenhydramine and Paroxetine 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; Paroxetine belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by diphenhydramine, plus additive anticholinergic and sedative effects.
What to do
Monitor for anticholinergic effects and sedation, and avoid regular use in elderly patients. Consider a less sedating antihistamine.
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 Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Paroxetine?
MediHelp rates the interaction as minor. Diphenhydramine and Paroxetine 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 and may modestly raise paroxetine levels, while paroxetine is itself a strong CYP2D6 inhibitor. Both have anticholinergic activity, so additive dry mouth, sedation, confusion and urinary retention may occur, especially in older adults.
How serious is the interaction between Diphenhydramine and Paroxetine?
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 anticholinergic effects and sedation, and avoid regular use in elderly patients. Consider a less sedating antihistamine.
What other medicines interact with Paroxetine?
MediHelp also lists interactions of Paroxetine with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Paroxetine page.
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