Drug interactions
Ketoconazole + Phenytoin
Severity: Major
Ketoconazole and Phenytoin: 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 raise phenytoin concentrations, risking nystagmus, ataxia and confusion. Phenytoin can in turn induce metabolism and lower ketoconazole levels, potentially causing antifungal failure.
What this interaction means in plain words
Ketoconazole and Phenytoin 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 belongs to Anti Fungals; Phenytoin belongs to Central Nervous System.
Why it happens
Ketoconazole inhibits CYP2C9/2C19 metabolism of phenytoin, while phenytoin induces CYP3A4 and reduces ketoconazole exposure.
What to do
Monitor phenytoin levels and clinical signs of toxicity, adjusting the dose as needed. Monitor antifungal response or choose an alternative antifungal that is not affected by enzyme induction.
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 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 Ketoconazole with Phenytoin?
MediHelp rates the interaction as major. Ketoconazole and Phenytoin 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 raise phenytoin concentrations, risking nystagmus, ataxia and confusion. Phenytoin can in turn induce metabolism and lower ketoconazole levels, potentially causing antifungal failure.
How serious is the interaction between Ketoconazole and Phenytoin?
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 phenytoin levels and clinical signs of toxicity, adjusting the dose as needed. Monitor antifungal response or choose an alternative antifungal that is not affected by enzyme induction.
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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