Drug interactions
Midazolam + Tramadol
Severity: Major
Midazolam and Tramadol: major interaction.
Last updated Sources: US FDA label
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
Midazolam combined with an opioid can cause profound sedation, respiratory depression, coma and death. Regulators have issued boxed warnings for opioid and benzodiazepine co-use. Midazolam is a CYP3A4 substrate, but tramadol is not a significant inhibitor.
What this interaction means in plain words
Midazolam and Tramadol 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.
Midazolam belongs to Central Nervous System; Tramadol belongs to Musculoskeletal.
Why it happens
Additive CNS and respiratory depression via opioid and GABA-A receptor effects.
What to do
Avoid concurrent use where possible; otherwise use the lowest doses and titrate slowly with continuous monitoring of respiration and oxygen saturation. Have resuscitation equipment 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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References
Other interactions of Tramadol
- Isocarboxazid + Tramadol Contraindicated
- Olanzapine / samidorphan + Tramadol Contraindicated
- Phenelzine + Tramadol Contraindicated
- Procarbazine + Tramadol Contraindicated
- Rasagiline + Tramadol Contraindicated
- Safinamide + Tramadol Contraindicated
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 Midazolam with Tramadol?
MediHelp rates the interaction as major. Midazolam and Tramadol 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. Midazolam combined with an opioid can cause profound sedation, respiratory depression, coma and death. Regulators have issued boxed warnings for opioid and benzodiazepine co-use. Midazolam is a CYP3A4 substrate, but tramadol is not a significant inhibitor.
How serious is the interaction between Midazolam and Tramadol?
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 concurrent use where possible; otherwise use the lowest doses and titrate slowly with continuous monitoring of respiration and oxygen saturation. Have resuscitation equipment available.
What other medicines interact with Tramadol?
MediHelp also lists interactions of Tramadol with, for example, Isocarboxazid, Olanzapine / samidorphan, Phenelzine. The full list is on the Tramadol page.
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