Drug interactions
Diphenhydramine + Oxycodone
Severity: Moderate
Diphenhydramine and Oxycodone: 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
Diphenhydramine adds to the sedative and respiratory depressant effects of oxycodone. As a CYP2D6 inhibitor it may also change oxycodone metabolism, though the clinical effect of this is uncertain because CYP3A4 is the dominant pathway.
What this interaction means in plain words
Diphenhydramine and Oxycodone 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; Oxycodone belongs to Musculoskeletal.
Why it happens
Additive CNS depression, plus weak CYP2D6 inhibition by diphenhydramine.
What to do
Monitor for excess sedation and respiratory depression, particularly in older adults, and avoid unnecessary co-prescription. Advise against driving until the response is known.
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 Oxycodone
- Alvimopan + Oxycodone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Oxycodone Contraindicated
- Isocarboxazid + Oxycodone Contraindicated
- Olanzapine / samidorphan + Oxycodone Contraindicated
- Oxycodone + Phenelzine Contraindicated
- Oxycodone + Sodium oxybate Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Oxycodone?
MediHelp rates the interaction as moderate. Diphenhydramine and Oxycodone 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 adds to the sedative and respiratory depressant effects of oxycodone. As a CYP2D6 inhibitor it may also change oxycodone metabolism, though the clinical effect of this is uncertain because CYP3A4 is the dominant pathway.
How serious is the interaction between Diphenhydramine and Oxycodone?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for excess sedation and respiratory depression, particularly in older adults, and avoid unnecessary co-prescription. Advise against driving until the response is known.
What other medicines interact with Oxycodone?
MediHelp also lists interactions of Oxycodone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Isocarboxazid. The full list is on the Oxycodone page.
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