Drug interactions
Fentanyl + Midazolam
Severity: Major
Fentanyl and Midazolam: major interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Opioids and benzodiazepines together produce additive sedation and respiratory depression, and this has caused fatal outcomes. Regulators have issued boxed warnings against routine concurrent use. Midazolam is also a CYP3A4 substrate and fentanyl may modestly reduce its clearance.
What this interaction means in plain words
Fentanyl and Midazolam can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Fentanyl belongs to Musculoskeletal; Midazolam belongs to Central Nervous System.
Why it happens
Additive CNS and respiratory depression through opioid and GABA-A receptor effects.
What to do
Avoid unless no alternative exists; if used, give the lowest doses for the shortest time. Monitor respiratory rate, oxygen saturation and sedation continuously in procedural settings, and have resuscitation equipment and reversal agents available.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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Other interactions of Fentanyl
- Alvimopan + Fentanyl Contraindicated
- Fentanyl + Isocarboxazid Contraindicated
- Fentanyl + Olanzapine / samidorphan Contraindicated
- Fentanyl + Phenelzine Contraindicated
- Fentanyl + Tranylcypromine Contraindicated
- Alfentanil + Fentanyl Major
Other interactions of Midazolam
- Atazanavir + Midazolam Contraindicated
- Cobicistat + Midazolam Contraindicated
- Darunavir + Midazolam Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Midazolam Contraindicated
- Fosamprenavir + Midazolam Contraindicated
- Indinavir + Midazolam Contraindicated
Frequently asked questions
Can I take Fentanyl with Midazolam?
MediHelp rates the interaction as major. Fentanyl and Midazolam can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Opioids and benzodiazepines together produce additive sedation and respiratory depression, and this has caused fatal outcomes. Regulators have issued boxed warnings against routine concurrent use. Midazolam is also a CYP3A4 substrate and fentanyl may modestly reduce its clearance.
How serious is the interaction between Fentanyl and Midazolam?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid unless no alternative exists; if used, give the lowest doses for the shortest time. Monitor respiratory rate, oxygen saturation and sedation continuously in procedural settings, and have resuscitation equipment and reversal agents available.
What other medicines interact with Fentanyl?
MediHelp also lists interactions of Fentanyl with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Fentanyl page.
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