Midazolam Injection and Tapentadol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tapentadol
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
An increased risk of CNS depression and an increased risk of respiratory depression, profound sedation, coma and death.
Interaction Deep Dive
Concomitant use of tapentadol with benzodiazepines can increase the risk of hypotension, respiratory depression, profound sedation, coma, opioid overdose and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. 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. Limit dosages and durations to the minimum required. If the decision is made to prescribe benzodiazepines concomitantly with tapentadol, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already taking tapentadol, prescribe a lower initial dose of the benzodiazepine and titrate based on clinical response. If tapentadol is initiated in a patient already taking benzodiazepines, prescribe the lowest initial dose of tapentadol and titrate based on clinical response. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose12.
Why it happens (mechanism)
Additive CNS depression
Literature reports
1 report — tap to read
Common questions
Can I take Midazolam Injection and Tapentadol together?
An increased risk of CNS depression and 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 Midazolam Injection and Tapentadol 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.
Questions for your pharmacist
- Does my dose of Midazolam Injection or Tapentadol 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: NUCYNTA(R) ER oral extended-release tablets, tapentadol oral extended-release tablets. Collegium Pharmaceutical Inc (per FDA), Stoughton, MA, 2023. DailyMed
- Product Information: NUCYNTA(R) oral tablets, tapentadol oral tablets. Collegium Pharmaceutical Inc (per FDA), Stoughton, MA, 2023. DailyMed
Keep reading about Tapentadol
Keep reading about Midazolam Injection
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