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Drug Interaction — RACP Adult Medicine MCQ

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ModerateClinical PharmacologyDrug InteractionRACP Adult Medicine

A 70-year-old man on warfarin for AF is commenced on fluconazole for oral candidiasis. Three days later his INR rises from 2.5 to 7.8. What is the mechanism of this interaction?

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Correct answer: B — Fluconazole inhibits CYP2C9, reducing warfarin metabolism

Fluconazole is a potent inhibitor of CYP2C9, the primary enzyme responsible for the metabolism of the more active S-enantiomer of warfarin. This results in markedly elevated INR. The interaction is predictable and dose-dependent. If fluconazole is necessary, the warfarin dose should be reduced by ~25–50% with frequent INR monitoring.

Reference: AMH – 2025 – Drug Interactions; eTG – 2025 – Antimicrobials