Simeprevir and Midazolam Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Simeprevir
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 exposure
Interaction Deep Dive
Use caution when coadministering oral midazolam, a CYP3A4 substrate, and simeprevir, an intestinal CYP3A4 inhibitor, as this may result in increased midazolam exposure and increased risk of adverse effects. During drug interaction studies in healthy adults (n=16), coadministration of oral midazolam with simeprevir increased midazolam AUC by 45% and Cmax by 31%1. If concomitant use is required, consider monitoring the patient for midazolam toxicity.
Why it happens (mechanism)
Inhibition of intestinal CYP3A4-mediated metabolism of midazolam by simeprevir
Literature reports
1 report — tap to read
a) During drug interaction studies in healthy adults (n=16), coadministration of a single dose of oral midazolam 0.075 mg/kg with simeprevir 150 mg orally once daily for 10 days resulted in increased midazolam AUC and Cmax (mean ratio of midazolam with to without simprevir: AUC, 1.45 [90% CI, 1.35 to 1.57]; Cmax, 1.31 [90% CI, 1.19 to 1.45]) 1.
Common questions
Can I take Simeprevir and Midazolam Nasal Spray together?
Increased midazolam exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simeprevir and Midazolam Nasal Spray interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Simeprevir 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 (1)
- Product Information: OLYSIO(TM) oral capsules, simeprevir oral capsules. Janssen Therapeutics (per manufacturer), Titusville, NJ, 2013.
Keep reading about Simeprevir
Keep reading about Midazolam Nasal Spray
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