Drug interactions
Codeine + Diphenhydramine
Severity: Moderate
Codeine and Diphenhydramine: 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 anticholinergic effects to codeine. It is also a CYP2D6 inhibitor and may modestly reduce conversion of codeine to morphine.
What this interaction means in plain words
Codeine and Diphenhydramine 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.
Codeine belongs to Musculoskeletal; Diphenhydramine belongs to Respiratory.
Why it happens
Additive CNS depression plus CYP2D6 inhibition that may decrease formation of morphine from codeine.
What to do
Monitor for excessive sedation, confusion and constipation, and check analgesic effect. Avoid in older adults where possible or use a non-sedating antihistamine.
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 Codeine
- Alvimopan + Codeine Contraindicated
- Codeine + Isocarboxazid Contraindicated
- Codeine + Olanzapine / samidorphan Contraindicated
- Codeine + Phenelzine Contraindicated
- Codeine + Tranylcypromine Contraindicated
- Alfentanil + Codeine Major
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Codeine with Diphenhydramine?
MediHelp rates the interaction as moderate. Codeine and Diphenhydramine 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 anticholinergic effects to codeine. It is also a CYP2D6 inhibitor and may modestly reduce conversion of codeine to morphine.
How serious is the interaction between Codeine and Diphenhydramine?
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 excessive sedation, confusion and constipation, and check analgesic effect. Avoid in older adults where possible or use a non-sedating antihistamine.
What other medicines interact with Codeine?
MediHelp also lists interactions of Codeine with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Codeine page.
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