Drug interactions
Midazolam + Nirmatrelvir / ritonavir
Severity: Contraindicated
Midazolam and Nirmatrelvir / ritonavir: contraindicated interaction.
Last updated Sources: US FDA label
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
Ritonavir-boosted nirmatrelvir strongly inhibits CYP3A and greatly increases midazolam exposure, especially after oral dosing. Marked sedation and respiratory depression can occur.
What this interaction means in plain words
Midazolam and Nirmatrelvir / ritonavir 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.
Why it happens
Ritonavir and nirmatrelvir inhibit intestinal and hepatic CYP3A4, reducing midazolam clearance.
What to do
Do not use oral midazolam. If IV midazolam is needed, reduce the dose and give it where respiratory monitoring and resuscitation are available.
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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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 Nirmatrelvir / ritonavir?
MediHelp rates the interaction as contraindicated. Midazolam and Nirmatrelvir / ritonavir 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. Ritonavir-boosted nirmatrelvir strongly inhibits CYP3A and greatly increases midazolam exposure, especially after oral dosing. Marked sedation and respiratory depression can occur.
How serious is the interaction between Midazolam and Nirmatrelvir / ritonavir?
MediHelp rates it contraindicated, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Do not use oral midazolam. If IV midazolam is needed, reduce the dose and give it where respiratory monitoring and resuscitation are available.
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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