Drug interactions
Midazolam + Phenobarbital
Severity: Major
Midazolam and Phenobarbital: 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
Phenobarbital causes additive sedation and respiratory depression with midazolam. With continued use it induces CYP3A4 and reduces midazolam exposure, so the effect changes over time.
What this interaction means in plain words
Midazolam and Phenobarbital 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.
Why it happens
Additive GABAergic CNS depression plus CYP3A4 induction by phenobarbital.
What to do
Monitor sedation and respiration closely and titrate to effect; expect higher midazolam requirements in chronic phenobarbital users.
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 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 Phenobarbital?
MediHelp rates the interaction as major. Midazolam and Phenobarbital 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. Phenobarbital causes additive sedation and respiratory depression with midazolam. With continued use it induces CYP3A4 and reduces midazolam exposure, so the effect changes over time.
How serious is the interaction between Midazolam and Phenobarbital?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor sedation and respiration closely and titrate to effect; expect higher midazolam requirements in chronic phenobarbital users.
What other medicines interact with Midazolam?
MediHelp also lists interactions of Midazolam with, for example, Atazanavir, Cobicistat, Darunavir. The full list is on the Midazolam page.
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