Drug interactions
Diphenhydramine + Morphine
Severity: Moderate
Diphenhydramine and Morphine: 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 is a sedating antihistamine that adds to morphine's drowsiness and psychomotor impairment. Although it inhibits CYP2D6, this has little effect on morphine, which is cleared mainly by glucuronidation.
What this interaction means in plain words
Diphenhydramine and Morphine 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; Morphine belongs to Musculoskeletal.
Why it happens
Additive central nervous system depression; CYP2D6 inhibition is not clinically important for morphine.
What to do
Monitor for excessive sedation, especially in older adults, and consider a non-sedating antihistamine. Counsel patients against driving.
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 Morphine
- Alvimopan + Morphine Contraindicated
- Isocarboxazid + Morphine Contraindicated
- Morphine + Olanzapine / samidorphan Contraindicated
- Morphine + Phenelzine Contraindicated
- Morphine + Tranylcypromine Contraindicated
- Alfentanil + Morphine Major
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Morphine?
MediHelp rates the interaction as moderate. Diphenhydramine and Morphine 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 is a sedating antihistamine that adds to morphine's drowsiness and psychomotor impairment. Although it inhibits CYP2D6, this has little effect on morphine, which is cleared mainly by glucuronidation.
How serious is the interaction between Diphenhydramine and Morphine?
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, especially in older adults, and consider a non-sedating antihistamine. Counsel patients against driving.
What other medicines interact with Morphine?
MediHelp also lists interactions of Morphine with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Morphine page.
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