Drug interactions
Diphenhydramine + Hydrocodone
Severity: Moderate
Diphenhydramine and Hydrocodone: 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 sedation and respiratory depression to hydrocodone. It also inhibits CYP2D6, but this has limited effect on hydrocodone.
What this interaction means in plain words
Diphenhydramine and Hydrocodone 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; Hydrocodone belongs to Musculoskeletal.
Why it happens
Additive CNS depression, with minor CYP2D6 inhibition.
What to do
Monitor for sedation and respiratory depression and warn about impaired driving. Use the lowest effective doses.
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 Hydrocodone
- Alvimopan + Hydrocodone Contraindicated
- Bupropion-naltrexone + Hydrocodone Contraindicated
- Hydrocodone + Isocarboxazid Contraindicated
- Hydrocodone + Olanzapine / samidorphan Contraindicated
- Hydrocodone + Phenelzine Contraindicated
- Alfentanil + Hydrocodone Major
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Hydrocodone?
MediHelp rates the interaction as moderate. Diphenhydramine and Hydrocodone 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 sedation and respiratory depression to hydrocodone. It also inhibits CYP2D6, but this has limited effect on hydrocodone.
How serious is the interaction between Diphenhydramine and Hydrocodone?
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 sedation and respiratory depression and warn about impaired driving. Use the lowest effective doses.
What other medicines interact with Hydrocodone?
MediHelp also lists interactions of Hydrocodone with, for example, Alvimopan, Bupropion-naltrexone, Isocarboxazid. The full list is on the Hydrocodone page.
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