Probenecid and Midazolam Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Probenecid
No brand names on recordMidazolam 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
Enhanced CNS depressive effects of midazolam
Interaction Deep Dive
In a controlled trial with midazolam there was an increased duration of unconsciousness in those patients taking probenecid when compared to controls1.
Why it happens (mechanism)
Altered plasma protein binding of midazolam
Literature reports
1 report — tap to read
a) An oral 1 gram probenecid dose given one hour before induction with midazolam 0.3 mg/kg produced a significantly shorter induction time than observed in the control group. The number of patients asleep was also significantly higher in the group pretreated with the probenecid, showing potentiation of midazolam. These effects are most likely due to changes in plasma protein binding of midazolam when probenecid is given 1.
Common questions
Can I take Probenecid and Midazolam Nasal Spray together?
Enhanced CNS depressive effects of midazolam Always confirm with your pharmacist or prescriber before making any change.
How serious is the Probenecid and Midazolam Nasal Spray interaction?
It is rated minor. Usually limited clinical impact.
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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Probenecid 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 anything you'd monitor while I'm on both?
References (1)
- Dundee JW, Halliday NJ, & McMurray TJ: Aspirin and probenecid pretreatment influences the potency of thiopentone and the onset of action of midazolam. Eur J Anaesthesiol 1986b; 3:247-251.
Keep reading about Probenecid
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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