Phenytoin and Voriconazole interaction

Phenytoin and Voriconazole: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Voriconazole label · effective 2026-06-02

Major

…Contraindicated Long Acting Barbiturates (e.g., phenobarbital, mephobarbital) (CYP450 Induction) Not Studied In Vivo or In Vitro , but Likely to Result in Significant Reduction Contraindicated Phenytoin (CYP450 Induction) Significantly Reduced Increase voriconazole maintenance dose from 4 mg/kg to 5 mg/kg IV every 12 hours or from 200 mg to 400 mg orally every 12 hours (100…

Drug interactionsnames PhenytoinView label on DailyMed
Moderate

Phenytoin (CYP2C9 Inhibition) Significantly Increased Frequent monitoring of phenytoin plasma concentrations and frequent monitoring of adverse effects related to phenytoin.

Drug interactionsnames PhenytoinView label on DailyMed
Moderate

Phenytoin or Efavirenz: With coadministration, increase maintenance oral and intravenous dosage of voriconazole ( 2.2 , 2.6 , 7 )

Drug interactionsnames PhenytoinView label on DailyMed
Moderate

Eszopiclone (CYP3A4 Inhibition) Not Studied In Vivo or In Vitro , but Drug Plasma Exposure Likely to be Increased which may Increase the Sedative Effect of Eszopiclone Dose reduction of eszopiclone is recommended.

Drug interactionsby drug classView label on DailyMed

From the Phenytoin label · effective 2024-12-24

Moderate

…may increase phenytoin serum levels Antiepileptic drugs Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole Antineoplastic agents Capecitabine, fluorouracil Antidepressants Fluoxetine, fluvoxamine, sertraline Gastric acid reducing agents H 2 antagonists (cimetidine), omeprazole…

Drug interactionsnames VoriconazoleView label on DailyMed
Moderate

Table 3: Drugs Affected by Phenytoin Interacting Agent Examples Drugs whose efficacy is impaired by phenytoin Azoles Fluconazole, ketoconazole, itraconazole, posaconazole, voriconazole Antineoplastic agents Irinotecan, paclitaxel, teniposide Delavirdine Phenytoin can substantially reduce the concentrations of delavirdine.

Drug interactionsnames VoriconazoleView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.