Drug interactions
Dextromethorphan + Diphenhydramine
Severity: Minor
Dextromethorphan and Diphenhydramine: 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 can increase dextromethorphan concentrations. Both drugs cause sedation, so additive drowsiness and impaired psychomotor performance may occur, as is common with combined cough and cold products.
What this interaction means in plain words
Dextromethorphan and Diphenhydramine have a small, usually unimportant interaction. Most people can take both; the pharmacist may still mention it so that any unexpected effect is recognised.
Dextromethorphan belongs to Respiratory; Diphenhydramine belongs to Respiratory.
Why it happens
Inhibition of CYP2D6 by diphenhydramine reduces dextromethorphan metabolism, with additive CNS depressant effects.
What to do
Advise patients to avoid driving or hazardous tasks until response is known and to avoid duplicate cough and cold products.
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 Dextromethorphan
- Dextromethorphan + Isocarboxazid Contraindicated
- Dextromethorphan + Linezolid Contraindicated
- Dextromethorphan + Phenelzine Contraindicated
- Dextromethorphan + Rasagiline Contraindicated
- Dextromethorphan + Safinamide Contraindicated
- Dextromethorphan + Selegiline Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Dextromethorphan with Diphenhydramine?
MediHelp rates the interaction as minor. Dextromethorphan and Diphenhydramine 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 can increase dextromethorphan concentrations. Both drugs cause sedation, so additive drowsiness and impaired psychomotor performance may occur, as is common with combined cough and cold products.
How serious is the interaction between Dextromethorphan and Diphenhydramine?
MediHelp rates it minor, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Advise patients to avoid driving or hazardous tasks until response is known and to avoid duplicate cough and cold products.
What other medicines interact with Dextromethorphan?
MediHelp also lists interactions of Dextromethorphan with, for example, Isocarboxazid, Linezolid, Phenelzine. The full list is on the Dextromethorphan page.
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