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Phenytoin-fluconazole interaction — GPhC CRA MCQ

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ModerateDrug InteractionsPhenytoin-fluconazole interactionGPhC CRA

A 55-year-old man on phenytoin 300 mg once daily for epilepsy has recently been started on fluconazole 50 mg once daily for recurrent oral candidiasis. He presents feeling dizzy and unsteady. What is the most likely cause of his symptoms?

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Correct answer: A — Fluconazole is inhibiting phenytoin metabolism leading to phenytoin toxicity

Fluconazole is a potent inhibitor of CYP2C9, which is the primary enzyme responsible for phenytoin metabolism. Concurrent use leads to increased phenytoin plasma concentrations, which can cause signs of toxicity including dizziness, nystagmus, ataxia, and confusion. Phenytoin has a narrow therapeutic index, making this interaction clinically significant. The phenytoin level should be checked and the dose may need reducing.

Reference: BNF Drug Interactions