Drug interactions
Hydrocodone + Midazolam
Severity: Major
Hydrocodone 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
Midazolam combined with an opioid markedly increases the risk of profound sedation, respiratory depression, apnea and death. This combination is a labeled boxed warning concern, particularly outside monitored settings.
What this interaction means in plain words
Hydrocodone 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.
Hydrocodone belongs to Musculoskeletal; Midazolam belongs to Central Nervous System.
Why it happens
Additive CNS and respiratory depression via opioid receptors and enhanced GABA-A activity.
What to do
Use only with continuous monitoring of oxygenation and ventilation and with resuscitation equipment available. Reduce and carefully titrate doses of both drugs.
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 Hydrocodone
- Alvimopan + Hydrocodone Contraindicated
- Bupropion-naltrexone + Hydrocodone Contraindicated
- Hydrocodone + Isocarboxazid Contraindicated
- Hydrocodone + Olanzapine / samidorphan Contraindicated
- Hydrocodone + Phenelzine Contraindicated
- Alfentanil + Hydrocodone 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 Hydrocodone with Midazolam?
MediHelp rates the interaction as major. Hydrocodone 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. Midazolam combined with an opioid markedly increases the risk of profound sedation, respiratory depression, apnea and death. This combination is a labeled boxed warning concern, particularly outside monitored settings.
How serious is the interaction between Hydrocodone 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: Use only with continuous monitoring of oxygenation and ventilation and with resuscitation equipment available. Reduce and carefully titrate doses of both drugs.
What other medicines interact with Hydrocodone?
MediHelp also lists interactions of Hydrocodone with, for example, Alvimopan, Bupropion-naltrexone, Isocarboxazid. The full list is on the Hydrocodone page.
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