Drug interactions
Midazolam + Oxycodone
Severity: Major
Midazolam and Oxycodone: 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 markedly increases the risk of profound sedation, respiratory depression, coma and death. Labeling for both classes warns about this combination.
What this interaction means in plain words
Midazolam and Oxycodone 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; Oxycodone belongs to Musculoskeletal.
Why it happens
Additive CNS and respiratory depression via opioid receptor agonism and GABA-A potentiation.
What to do
Use only in monitored settings with careful dose titration, continuous pulse oximetry and resuscitation equipment available. Reduce doses of both drugs and avoid outpatient co-prescribing where possible.
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 Oxycodone
- Alvimopan + Oxycodone Contraindicated
- Calcium / magnesium / potassium / sodium oxybates + Oxycodone Contraindicated
- Isocarboxazid + Oxycodone Contraindicated
- Olanzapine / samidorphan + Oxycodone Contraindicated
- Oxycodone + Phenelzine Contraindicated
- Oxycodone + Sodium oxybate 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 Oxycodone?
MediHelp rates the interaction as major. Midazolam and Oxycodone 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 markedly increases the risk of profound sedation, respiratory depression, coma and death. Labeling for both classes warns about this combination.
How serious is the interaction between Midazolam and Oxycodone?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Use only in monitored settings with careful dose titration, continuous pulse oximetry and resuscitation equipment available. Reduce doses of both drugs and avoid outpatient co-prescribing where possible.
What other medicines interact with Oxycodone?
MediHelp also lists interactions of Oxycodone with, for example, Alvimopan, Calcium / magnesium / potassium / sodium oxybates, Isocarboxazid. The full list is on the Oxycodone page.
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