Cobicistat and Midazolam Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cobicistat
Midazolam Nasal Spray
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
Increased midazolam plasma concentrations and increased risk for serious adverse effects including, prolonged or increased sedation or respiratory depression
Interaction Deep Dive
Coadministration of cobicistat, a CYP3A4 inhibitor2, and oral midazolam, which is extensively metabolized by CYP3A4 1, is contraindicated due to an increased risk for serious adverse effects including, prolonged or increased sedation or respiratory depression. Caution is advised with coadministration of cobicistat and parenteral midazolam. If concomitant use of cobicistat and parenteral midazolam is required, the patient should be closely monitored for midazolam adverse effects (excessive sedation, confusion, respiratory depression) and a reduced midazolam dose should be considered, especially if more than a single midazolam dose is administered 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated midazolam metabolism by cobicistat
Common questions
Can I take Cobicistat and Midazolam Nasal Spray together?
Increased midazolam plasma concentrations and increased risk for serious adverse effects including, prolonged or increased sedation or respiratory depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cobicistat and Midazolam Nasal Spray 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 Cobicistat or Midazolam Nasal Spray 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 (2)
- Product Information: midazolam hcl oral syrup, midazolam hcl oral syrup. Roxane Laboratories,Inc, Columbus, OH, 2007. DailyMed
- Product Information: STRIBILD(TM) oral tablets, elvitegravir cobicistat emtricitabine tenofovir disoproxil fumarate oral tablets. Gilead Sciences, Inc. (per manufacturer), Foster City, CA, 2012. DailyMed
Keep reading about Cobicistat
Keep reading about Midazolam Nasal Spray
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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