Midazolam Injection and Fosaprepitant: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fosaprepitant
Midazolam Injection
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
Coadministration of fosaprepitant or aprepitant (weak to moderate CYP3A4 inhibitor) with midazolam (CYP3A4 substrate may result in increased midazolam exposure. Monitor for benzodiazepine-related adverse reactions12. In studies conducted with midazolam, coadministration of fosaprepitant or aprepitant under varying conditions resulted in increased midazolam AUC. Monitoring is recommended and the dose of IV midazolam should be reduced based on the clinical status of patient (eg, geriatric) 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of midazolam
Literature reports
4 reports — tap to read
a) In an open-label, randomized, crossover study (n=10), coadministration of fosaprepitant 150 mg IV on day 1 with midazolam 2 mg orally on days 1 and 4 increased the midazolam AUC by 1.77-fold on day 1 compared with administration of midazolam alone 4. Midazolam AUC was unchanged on day 4 5.
b) A single oral dose of midazolam 2 mg on day 1 and day 5 coadministered with oral aprepitant 125 mg on day 1 and 80 mg/day on days 2 through 5 increased midazolam AUC by 2.3-fold on day 1 and 3.3-fold on day 5 2.
c) Coadministration of single IV dose of fosaprepitant 150 mg on Day 1 and oral midazolam 2 mg on Days 1 and 4, increased midazolam AUC by 1.8-fold on Day 1 and had no effect on Day 4 6.
d) Concomitant administration of midazolam 2 mg IV, given 1 hour after a single oral dose of aprepitant 125 mg, increased the midazolam AUC by 1.5-fold. Administration of midazolam 2 mg IV and oral aprepitant 125 mg on day 1, oral aprepitant 80 mg/day on days 2 and 3, and additional doses of midazolam 2 mg IV on days 4, 8, and 15 increased the midazolam AUC by 25% on day 4 and decreased the midazolam AUC by 19% on day 8 and decreased the midazolam AUC by 4% on Day 15 2.
Common questions
Can I take Midazolam Injection and Fosaprepitant together?
Increased midazolam exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Midazolam Injection and Fosaprepitant interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
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 Midazolam Injection or Fosaprepitant 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 anything you'd monitor while I'm on both?
References (6)
- Product Information: FOCINVEZ intravenous injection, fosaprepitant intravenous injection. Spes Pharmaceuticals Inc (per FDA), North Brunswick, NJ, 2023. DailyMed
- Product Information: EMEND(R) oral capsules, oral suspension, aprepitant oral capsules, oral suspension. Merck Sharp & Dohme Corp (per FDA), Whitehouse Station, NJ, 2019. DailyMed
- Product Information: EMEND(R) oral capsules, aprepitant oral capsules. Merck Sharp & Dohme Corp. (per manufacturer), Whitehouse Station, NJ, 2015. DailyMed
- Marbury TC, Ngo PL, Shadle CR, et al: Pharmacokinetics of oral dexamethasone and midazolam when administered with single-dose intravenous 150 mg fosaprepitant in healthy adult subjects. J Clin Pharmacol 2011; 51(12):1712-1720. PubMed
- Product Information: EMEND(R) oral capsules, aprepitqant oral capsules. Merck Sharp & Dohme Corp. (per FDA), Whitehouse Station, NJ, 2013. DailyMed
- Product Information: EMEND(R) intravenous injection, fosaprepitant intravenous injection. Merck Sharp & Dohme Corp (per FDA), Whitehouse Station, NJ, 2022. DailyMed
Keep reading about Fosaprepitant
Keep reading about Midazolam Injection
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