Drug interactions
Ketoconazole + Midazolam
Severity: Contraindicated
Ketoconazole and Midazolam: contraindicated 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
Ketoconazole greatly increases systemic exposure to oral midazolam, causing prolonged and intensified sedation and respiratory depression. Oral midazolam is contraindicated with strong CYP3A4 inhibitors.
What this interaction means in plain words
Ketoconazole and Midazolam are not normally used together. Taking them at the same time is expected to cause harm or make one of them unsafe, so a different medicine is usually chosen for one of the two.
Ketoconazole belongs to Anti Fungals; Midazolam belongs to Central Nervous System.
Why it happens
Ketoconazole strongly inhibits intestinal and hepatic CYP3A4, reducing midazolam first-pass and systemic clearance.
What to do
Avoid oral midazolam. For single IV doses, use a reduced dose with close monitoring of sedation and respiration, or choose a benzodiazepine not cleared by CYP3A4 such as lorazepam.
What to ask your pharmacist
- Is there an alternative to one of these two medicines for me?
- If both are essential, who is monitoring me and how often?
- Which symptoms mean I should stop and seek help straight away?
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Other interactions of Ketoconazole
- Alfuzosin + Ketoconazole Contraindicated
- Alprazolam + Ketoconazole Contraindicated
- Avanafil + Ketoconazole Contraindicated
- Conivaptan + Ketoconazole Contraindicated
- Dihydroergotamine intranasal + Ketoconazole Contraindicated
- Dihydroergotamine + Ketoconazole Contraindicated
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
Frequently asked questions
Can I take Ketoconazole with Midazolam?
MediHelp rates the interaction as contraindicated. Ketoconazole and Midazolam are not normally used together. Taking them at the same time is expected to cause harm or make one of them unsafe, so a different medicine is usually chosen for one of the two. Ketoconazole greatly increases systemic exposure to oral midazolam, causing prolonged and intensified sedation and respiratory depression. Oral midazolam is contraindicated with strong CYP3A4 inhibitors.
How serious is the interaction between Ketoconazole and Midazolam?
MediHelp rates it contraindicated, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid oral midazolam. For single IV doses, use a reduced dose with close monitoring of sedation and respiration, or choose a benzodiazepine not cleared by CYP3A4 such as lorazepam.
What other medicines interact with Ketoconazole?
MediHelp also lists interactions of Ketoconazole with, for example, Alfuzosin, Alprazolam, Avanafil. The full list is on the Ketoconazole page.
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