Itraconazole and Midazolam Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Itraconazole
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 and an increased risk of midazolam-related adverse effects (respiratory depression)
Interaction Deep Dive
Coadministration of itraconazole and oral midazolam, as well as use for up to 2 weeks following itraconazole discontinuation, is contraindicated due to a risk of significantly increased midazolam exposure23 and a risk of respiratory depression 4. With IV injection of midazolam, monitor for adverse reactions of midazolam. Midazolam dose reduction may be necessary 3. The AUC, Cmax, and t1/2 of midazolam significantly increased when midazolam and itraconazole were coadministered 451.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated midazolam metabolism by itraconazole
Literature reports
3 reports — tap to read
a) Oral midazolam coadministered with itraconazole 100 to 200 mg daily resulted in an 80% to 240% increase in midazolam Cmax and a 240% to 980% increase in midazolam AUC 4.
b) The Cmax and t(1/2) of midazolam were increased by concomitant administration of itraconazole. Nine healthy volunteers received itraconazole 200 mg/day for 4 days, along with 15 mg oral midazolam before the first treatment and 7.5 mg on the last day of itraconazole. During itraconazole or 4 days after, the AUC for midazolam were 8 and 2.6 times larger, respectively, than before itraconazole. Cmax and t(1/2) were also increased by itraconazole; 4 days after itraconazole treatment the increase in t(1/2) of midazolam was no longer significant. Increased plasma concentrations of midazolam may result in an increased risk for drowsiness, somnolence, and respiratory depression 5.
c) A randomized, double-blind, placebo-controlled study examined the effects of itraconazole or fluconazole on midazolam in 12 healthy volunteers over a 6-day period. Patients were assigned to a regimen of itraconazole, fluconazole, or placebo that started on day 1 and continued through day 6. Patients received 7.5 mg oral midazolam on day 1 and day 6 of the study, and 0.05 mg/kg intravenous midazolam on day 4. Itraconazole and fluconazole reduced the mean plasma clearance of intravenous midazolam by 69% and 51%, respectively. On day 1, itraconazole and fluconazole increased the mean AUC 3.5-fold and increased the Cmax 1.8-fold and 2.5-fold, respectively. Both antimycotics increased the half-life of midazolam. The effect of itraconazole was greater on day 6; oral midazolam AUC, Cmax, and half-life on day 6 were almost doubled compared to day 1 of treatment. For fluconazole, the effects on midazolam on day 1 and day 6 were similar 1.
Common questions
Can I take Itraconazole and Midazolam Nasal Spray together?
Increased midazolam exposure and an increased risk of midazolam-related adverse effects (respiratory depression) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Itraconazole 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 "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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Itraconazole 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 (5)
- Olkkola KT, Ahonen J, & Neuvonen PJ: The effect of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth Analg 1996; 82:511-516. DOI
- Product Information: SPORANOX(R) oral solution, itraconazole oral solution. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2024. DailyMed
- Product Information: SPORANOX(R) oral capsules, itraconazole oral capsules. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2024. DailyMed
- Product Information: midazolam HCl oral syrup, midazolam HCl oral syrup. Roxane Laboratories, Inc. (per DailyMed), Columbus, OH, 2012. DailyMed
- Backman J, Kivisto K, Olkkola K, et al: The area under the plasma concentration-time curve for oral midazolam is 400-fold larger during treatment with itraconazole than with rifampicin. Eur J Clin Pharmacol 1998; 54:53-58. PubMed
Keep reading about Itraconazole
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist