Warfarin CYP2C9 Drug Interactions and INR
Warfarin is a narrow therapeutic index anticoagulant metabolized primarily by CYP2C9 — making it highly susceptible to drug interactions that shift INR into dangerous ranges. This topic appears frequently on USMLE Step 1 and Step 2 CK, pharmacy board exams, and clinical decision-making. Understanding which drugs induce or inhibit CYP2C9 predicts bleeding risk and thrombotic complications before they occur.
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5 CardsHow does fluconazole raise INR in a patient on warfarin?
What is the target INR range for most patients on warfarin?
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What is the difference between CYP2C9 inducers and inhibitors for warfarin?
Inhibitors (fluconazole, amiodarone) slow warfarin metabolism → warfarin accumulates → ↑ INR → ↑ bleeding risk. Inducers (rifampin, carbamazepine) speed warfarin metabolism → warfarin depleted → ↓ INR → ↑ thrombosis risk.
How many days does it take for a CYP2C9 drug interaction to affect INR?
2–5 days for most inhibitors, because warfarin has a half-life of ~36–42 hours. INR should be rechecked 3–5 days after starting or stopping any CYP2C9-interacting drug.
Why is warfarin's narrow therapeutic index clinically significant?
Small changes in warfarin plasma levels cause disproportionate INR shifts. At INR < 2, patients risk stroke or DVT. At INR > 4, spontaneous bleeding, including intracranial hemorrhage, becomes a serious concern.
How do I memorize CYP2C9 inhibitors that interact with warfarin?
Remember inhibitors as FAMT: Fluconazole, Amiodarone, Metronidazole, TMP-SMX. For inducers, recall RPCPS: Rifampin, Phenytoin, Carbamazepine, Phenobarbital, St. John's Wort.