MAJOR — Use With Caution
FDA-documented interaction. Monitor phenytoin levels closely. Dose reduction may be needed. Consider alternative antifungals.
Evidence level: STRONG
Fluconazole (Diflucan) blocks the enzyme that breaks down phenytoin (Dilantin), causing phenytoin levels to rise to potentially toxic levels. Since phenytoin has a narrow safety range, even small increases can cause toxicity.
Fluconazole inhibits CYP2C9, the primary metabolic pathway for phenytoin. Can significantly increase phenytoin levels, causing toxicity. FDA labels for both drugs document this.
Get your phenytoin level checked within a few days of starting fluconazole. Report any dizziness, double vision, or unsteadiness immediately.
Take Phenytoin at exactly the same times each day — consistency is critical for seizure control. Fluconazole follows its prescribed schedule. Antiepileptics are potent enzyme inducers that can change how your body processes many other medications.
Higher risk for: those on multiple antiepileptics (enzyme induction/inhibition), liver impairment, elderly, pregnant individuals (teratogenicity concerns), or those with recent dose changes.
Dizziness, double vision, slurred speech, unsteady walking, nausea, confusion, abnormal eye movements
Monitor phenytoin levels within 3-5 days. Consider phenytoin dose reduction. Alternative antifungals may avoid this interaction.
Antiepileptic drug levels are sensitive to enzyme inducers and inhibitors. Discuss any changes with your neurologist before adding new substances. Safer supplement options: magnesium, omega-3s, and B vitamins are generally well-tolerated alongside seizure medications.
Fluconazole (Diflucan) blocks the enzyme that breaks down phenytoin (Dilantin), causing phenytoin levels to rise to potentially toxic levels. Since phenytoin has a narrow safety range, even small increases can cause toxicity.
Take Phenytoin at exactly the same times each day — consistency is critical for seizure control. Fluconazole follows its prescribed schedule. Antiepileptics are potent enzyme inducers that can change how your body processes many other medications.
Dizziness, double vision, slurred speech, unsteady walking, nausea, confusion, abnormal eye movements
Antiepileptic drug levels are sensitive to enzyme inducers and inhibitors. Discuss any changes with your neurologist before adding new substances. Safer supplement options: magnesium, omega-3s, and B vitamins are generally well-tolerated alongside seizure medications.
Monitor phenytoin levels within 3-5 days. Consider phenytoin dose reduction. Alternative antifungals may avoid this interaction.
Or browse the full interaction database (121,000+ pairs).