Drug interactions
Clozapine + Phenobarbital
Severity: Major
Clozapine and Phenobarbital: major interaction.
Last updated Sources: UK 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
Phenobarbital induces hepatic enzymes and can lower clozapine exposure, potentially causing relapse. It also adds to sedation and respiratory depression.
What this interaction means in plain words
Clozapine 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
Induction of CYP1A2 and CYP3A4 increases clozapine clearance, plus additive CNS depression.
What to do
Monitor clinical response and sedation and consider therapeutic drug monitoring of clozapine. Adjust clozapine dose when phenobarbital is started or stopped.
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 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 Phenobarbital?
MediHelp rates the interaction as major. Clozapine 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 induces hepatic enzymes and can lower clozapine exposure, potentially causing relapse. It also adds to sedation and respiratory depression.
How serious is the interaction between Clozapine 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 clinical response and sedation and consider therapeutic drug monitoring of clozapine. Adjust clozapine dose when phenobarbital is started or stopped.
What other medicines interact with Clozapine?
MediHelp also lists interactions of Clozapine with, for example, Deferiprone, Irinotecan, Pimozide. The full list is on the Clozapine page.
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