Drug interactions
Midazolam + Nefazodone
Severity: Major
Midazolam and Nefazodone: major interaction.
Last updated Sources: UK SmPC
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
Nefazodone is a strong CYP3A4 inhibitor and markedly raises midazolam exposure. This can cause prolonged sedation, amnesia and respiratory depression, especially with oral dosing.
What this interaction means in plain words
Midazolam and Nefazodone can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Why it happens
Inhibition of CYP3A4-mediated hepatic and intestinal metabolism of midazolam.
What to do
Avoid oral midazolam, and if parenteral midazolam is needed use a substantially reduced dose with careful titration and monitoring of respiration. Consider a benzodiazepine not metabolized by CYP3A4, such as lorazepam.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
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 Midazolam with Nefazodone?
MediHelp rates the interaction as major. Midazolam and Nefazodone can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Nefazodone is a strong CYP3A4 inhibitor and markedly raises midazolam exposure. This can cause prolonged sedation, amnesia and respiratory depression, especially with oral dosing.
How serious is the interaction between Midazolam and Nefazodone?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid oral midazolam, and if parenteral midazolam is needed use a substantially reduced dose with careful titration and monitoring of respiration. Consider a benzodiazepine not metabolized by CYP3A4, such as lorazepam.
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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