Oxycodone and Midazolam Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Oxycodone
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
An increased risk of respiratory depression, profound sedation, coma and death
Interaction Deep Dive
Coadministration of oxyCODONE and benzodiazepines may result in additive CNS depression and an increased risk of respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate. If concomitant use is necessary, use the lowest effective dosage and minimum duration of use. Monitor for sedation and respiratory depression and strongly consider prescribing naloxone for the emergency treatment of opioid overdose. Strongly consider prescribing naloxone for the emergency treatment of opioid overdose1.
Why it happens (mechanism)
Additive CNS depression
Literature reports
1 report — tap to read
a) Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone 2.
Common questions
Can I take Oxycodone and Midazolam Nasal Spray together?
An increased risk of respiratory depression, profound sedation, coma and death Always confirm with your pharmacist or prescriber before making any change.
How serious is the Oxycodone 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 "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 Oxycodone 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: PERCODAN(R) oral tablets, oxycodone aspirin oral tablets. Endo Pharmaceuticals Inc. (per FDA), Malvern, PA, 2023.
- Product Information: OXYCONTIN(R) oral extended-release tablets, oxycodone HCl oral extended-release tablets. Purdue Pharma LP (per FDA), Stamford, CT, 2023. DailyMed
Keep reading about Oxycodone
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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