Drug interactions
Clozapine + Primidone
Severity: Major
Clozapine and Primidone: 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
Primidone is metabolized to phenobarbital and induces hepatic enzymes, which can reduce clozapine concentrations and efficacy. It also adds to sedation.
What this interaction means in plain words
Clozapine and Primidone 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; Primidone belongs to Central Nervous System.
Why it happens
Enzyme induction (CYP1A2, CYP3A4) increases clozapine clearance, plus additive CNS depression.
What to do
Monitor clinical response and sedation and consider clozapine plasma levels. Adjust clozapine dose when primidone 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
Other interactions of Primidone
- Lorlatinib + Primidone Contraindicated
- Lurasidone + Primidone Contraindicated
- Primidone + Ranolazine Contraindicated
- Primidone + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
- Primidone + Voriconazole Contraindicated
- Abiraterone + Primidone Major
Frequently asked questions
Can I take Clozapine with Primidone?
MediHelp rates the interaction as major. Clozapine and Primidone 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. Primidone is metabolized to phenobarbital and induces hepatic enzymes, which can reduce clozapine concentrations and efficacy. It also adds to sedation.
How serious is the interaction between Clozapine and Primidone?
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 clozapine plasma levels. Adjust clozapine dose when primidone 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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