Phenytoin and fluorouracil interaction.

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Gilbar PJ, Brodribb TR

Phenytoin and fluorouracil interaction.

Ann Pharmacother. 2001 Nov;35(11):1367-70. doi: 10.1345/aph.1A051.

PubMed ID

11724084 [ View in PubMed

]

Abstract

OBJECTIVE: To report a probable drug interaction between phenytoin and fluorouracil. CASE REPORT: A 66-year-old white man started adjuvant chemotherapy for colon cancer with weekly bolus injections of fluorouracil and leucovorin calcium. He had been taking phenytoin 300 mg/d for epilepsy for more than four years. Eleven weeks later, the patient was reported to be unsteady on his feet and had fallen several times. The serum phenytoin concentration at that time was 36 microg/mL. The phenytoin dosage was decreased and the symptoms resolved. Phenytoin concentrations were monitored and the dosages were adjusted accordingly throughout the remaining 15 weeks of treatment with fluorouracil. After completion of chemotherapy, the phenytoin dose was gradually increased to the original dose with no signs of toxicity. DISCUSSION: Phenytoin is principally metabolized by CYP2C9. Inhibition of that isoenzyme by fluorouracil, and possible interference with its synthesis, appears to be the most likely cause of this interaction. The reduction in saturating substrate concentration of phenytoin was reduced as a result of this interaction, thus causing decreased clearance and increased serum concentrations. No previous interaction between phenytoin and fluorouracil has been reported. Both phenytoin and warfarin are metabolized by CYP269 and therefore exhibit the same spectrum of interactions when that isoenzyme is inhibited. Interactions have been reported with concurrent administration of warfarin and fluorouracil. CONCLUSIONS: The nature and extent of this phenytoin-fluorouracil interaction should be elucidated by in vitro investigations and a prospective study. Until then, clinicians should be aware of this potentially serious drug interaction and monitor patients closely for phenytoin toxicity.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Floxuridine	Cytochrome P450 2C9	Protein	Humans	Unknown	Inhibitor	Details
Fluorouracil	Cytochrome P450 2C9	Protein	Humans	Unknown	Inhibitor	Details

Drug Interactions

Drugs	Interaction
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