Drug interactions
Clozapine + Ketoconazole
Severity: Major
Clozapine and Ketoconazole: major 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
Ketoconazole may increase clozapine concentrations, raising the risk of sedation, seizures, hypotension and cardiac effects. Both can also affect the QT interval.
What this interaction means in plain words
Clozapine and Ketoconazole 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; Ketoconazole belongs to Anti Fungals.
Why it happens
Ketoconazole inhibits CYP3A4, one of the enzymes contributing to clozapine metabolism.
What to do
Monitor clozapine levels and clinical signs of toxicity, and reduce the clozapine dose if needed. Consider an ECG when starting the combination.
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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Other interactions of Ketoconazole
- Alfuzosin + Ketoconazole Contraindicated
- Alprazolam + Ketoconazole Contraindicated
- Avanafil + Ketoconazole Contraindicated
- Conivaptan + Ketoconazole Contraindicated
- Dihydroergotamine intranasal + Ketoconazole Contraindicated
- Dihydroergotamine + Ketoconazole 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 Ketoconazole?
MediHelp rates the interaction as major. Clozapine and Ketoconazole 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. Ketoconazole may increase clozapine concentrations, raising the risk of sedation, seizures, hypotension and cardiac effects. Both can also affect the QT interval.
How serious is the interaction between Clozapine and Ketoconazole?
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 clozapine levels and clinical signs of toxicity, and reduce the clozapine dose if needed. Consider an ECG when starting the combination.
What other medicines interact with Ketoconazole?
MediHelp also lists interactions of Ketoconazole with, for example, Alfuzosin, Alprazolam, Avanafil. The full list is on the Ketoconazole page.
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