Drug interactions
Clozapine + Phenytoin
Severity: Moderate
Clozapine and Phenytoin: moderate 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
Phenytoin induces hepatic enzymes and can lower clozapine plasma concentrations, which may lead to loss of antipsychotic control. Phenytoin also adds to the seizure and bone marrow concerns seen with clozapine. When phenytoin is stopped, clozapine levels can rise substantially.
What this interaction means in plain words
Clozapine and Phenytoin can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Clozapine belongs to Central Nervous System; Phenytoin belongs to Central Nervous System.
Why it happens
Phenytoin induces CYP1A2 and CYP3A4, increasing clozapine clearance.
What to do
Monitor psychiatric response and consider clozapine plasma levels when phenytoin is started, and raise the clozapine dose cautiously if needed. When phenytoin is withdrawn, reduce clozapine as needed and watch for toxicity such as sedation, hypotension and seizures.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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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 Phenytoin
- Artemether / lumefantrine + Phenytoin Contraindicated
- Bictegravir + Phenytoin Contraindicated
- Cabotegravir + Phenytoin Contraindicated
- Doravirine + Phenytoin Contraindicated
- Elbasvir / grazoprevir + Phenytoin Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Phenytoin Contraindicated
Frequently asked questions
Can I take Clozapine with Phenytoin?
MediHelp rates the interaction as moderate. Clozapine and Phenytoin can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Phenytoin induces hepatic enzymes and can lower clozapine plasma concentrations, which may lead to loss of antipsychotic control. Phenytoin also adds to the seizure and bone marrow concerns seen with clozapine. When phenytoin is stopped, clozapine levels can rise substantially.
How serious is the interaction between Clozapine and Phenytoin?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor psychiatric response and consider clozapine plasma levels when phenytoin is started, and raise the clozapine dose cautiously if needed. When phenytoin is withdrawn, reduce clozapine as needed and watch for toxicity such as sedation, hypotension and seizures.
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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