Drug interactions
Midazolam + Phenytoin
Severity: Moderate
Midazolam and Phenytoin: 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
Phenytoin can reduce midazolam concentrations, especially after oral dosing, resulting in diminished sedative or anticonvulsant effect. The reduction can be substantial with chronic phenytoin use.
What this interaction means in plain words
Midazolam and Phenytoin 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.
Midazolam belongs to Central Nervous System; Phenytoin belongs to Central Nervous System.
Why it happens
Phenytoin induces CYP3A4, increasing midazolam clearance and first-pass metabolism.
What to do
Titrate midazolam to clinical response and expect higher dose requirements; consider an alternative benzodiazepine not reliant on CYP3A4 if oral dosing is needed.
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 Phenytoin
- Artemether / lumefantrine + Phenytoin Contraindicated
- Bictegravir + Phenytoin Contraindicated
- Cabotegravir + Phenytoin Contraindicated
- Doravirine + Phenytoin Contraindicated
- Elbasvir / grazoprevir + Phenytoin Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Phenytoin Contraindicated
Frequently asked questions
Can I take Midazolam with Phenytoin?
MediHelp rates the interaction as moderate. Midazolam and Phenytoin 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. Phenytoin can reduce midazolam concentrations, especially after oral dosing, resulting in diminished sedative or anticonvulsant effect. The reduction can be substantial with chronic phenytoin use.
How serious is the interaction between Midazolam and Phenytoin?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Titrate midazolam to clinical response and expect higher dose requirements; consider an alternative benzodiazepine not reliant on CYP3A4 if oral dosing is needed.
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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