CLINICAL QUESTION

A patient on warfarin 5mg/day is started on fluconazole. What is the PRIMARY pharmacokinetic interaction and what INR change do you expect?

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ANSWER + CLINICAL PEARL

Fluconazole inhibits CYP2C9, the primary enzyme metabolising warfarin's S-enantiomer (more potent). Result: ↓ warfarin clearance → ↑ plasma levels → ↑ INR (can rise from 2.4 to >6). 💎 Pearl: Monitor INR within 3–5 days of any azole addition. Reduce warfarin dose by 25–50%.