Drug interactions
Diphenhydramine + Midazolam
Severity: Moderate
Diphenhydramine and Midazolam: 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
Both drugs cause sedation and psychomotor impairment, so concurrent use produces greater drowsiness than either alone. Older patients may experience confusion, falls or respiratory depression.
What this interaction means in plain words
Diphenhydramine and Midazolam 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; Midazolam belongs to Central Nervous System.
Why it happens
Additive CNS depression from benzodiazepine GABA-A potentiation and central H1 antagonism.
What to do
Reduce midazolam dose and titrate to effect. Monitor sedation level and respiratory status, especially in older adults.
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 Midazolam
- Atazanavir + Midazolam Contraindicated
- Cobicistat + Midazolam Contraindicated
- Darunavir + Midazolam Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Midazolam Contraindicated
- Fosamprenavir + Midazolam Contraindicated
- Indinavir + Midazolam Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Midazolam?
MediHelp rates the interaction as moderate. Diphenhydramine and Midazolam 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. Both drugs cause sedation and psychomotor impairment, so concurrent use produces greater drowsiness than either alone. Older patients may experience confusion, falls or respiratory depression.
How serious is the interaction between Diphenhydramine and Midazolam?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Reduce midazolam dose and titrate to effect. Monitor sedation level and respiratory status, especially in older adults.
What other medicines interact with Midazolam?
MediHelp also lists interactions of Midazolam with, for example, Atazanavir, Cobicistat, Darunavir. The full list is on the Midazolam page.
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