Midazolam Injection and Nirmatrelvir: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Midazolam Injection
Nirmatrelvir
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of extreme sedation and respiratory depression
Interaction Deep Dive
Concomitant use of oral midazolam and nirmatrelvir/ritonavir is contraindicated due to potential for extreme sedation and respiratory depression. Coadministration of parenteral midazolam and nirmatrelvir/ritonavir should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation. Consider reducing the dosage of midazolam, especially if more than a single dose of midazolam is administered1.
Why it happens (mechanism)
Increased midazolam serum concentration
Common questions
Can I take Midazolam Injection and Nirmatrelvir together?
An increased risk of extreme sedation and respiratory depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Midazolam Injection and Nirmatrelvir interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Midazolam Injection or Nirmatrelvir need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Pfizer Inc: Fact sheet for healthcare providers: Emergency Use Authorization for PAXLOVID(TM). US Food & Drug Administration (FDA). Silver Spring, MD. 2021.
Keep reading about Midazolam Injection
Keep reading about Nirmatrelvir
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