Drug interactions
Clozapine + Midazolam
Severity: Major
Clozapine and Midazolam: major interaction.
Last updated Sources: EMA SmPC
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
Concurrent benzodiazepine and clozapine use has been associated with marked sedation, hypotension, respiratory depression and rarely collapse. The risk is highest during clozapine initiation and with parenteral benzodiazepines.
What this interaction means in plain words
Clozapine 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.
Clozapine belongs to Central Nervous System; Midazolam belongs to Central Nervous System.
Why it happens
Additive CNS and respiratory depression and hypotension from GABA-A potentiation and clozapine's multi-receptor blockade.
What to do
Avoid parenteral midazolam where possible, or use reduced doses with close monitoring of blood pressure, respiration and sedation. Take particular care when clozapine is being initiated or titrated.
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
Other interactions of Clozapine
- Clozapine + Deferiprone Contraindicated
- Clozapine + Irinotecan Contraindicated
- Clozapine + Pimozide Contraindicated
- Clozapine + Thioridazine Contraindicated
- Acalabrutinib + Clozapine Major
- Adagrasib + Clozapine Major
Frequently asked questions
Can I take Clozapine with Midazolam?
MediHelp rates the interaction as major. Clozapine 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. Concurrent benzodiazepine and clozapine use has been associated with marked sedation, hypotension, respiratory depression and rarely collapse. The risk is highest during clozapine initiation and with parenteral benzodiazepines.
How serious is the interaction between Clozapine 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 parenteral midazolam where possible, or use reduced doses with close monitoring of blood pressure, respiration and sedation. Take particular care when clozapine is being initiated or titrated.
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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