Major
Established
Mô tả
Phenytoin and warfarin have a complex bidirectional interaction: phenytoin initially inhibits warfarin metabolism (raising INR) but then induces it (lowering INR), making anticoagulation management unpredictable.
Cơ chế
Acute phenytoin administration inhibits CYP2C9; with chronic use, CYP2C9 induction predominates, increasing warfarin clearance. Warfarin may displace phenytoin from albumin and inhibit its metabolism.
Ý nghĩa lâm sàng
Both bleeding (early) and thromboembolic (late) events have occurred; warfarin can also raise phenytoin levels, risking phenytoin toxicity.
Xử trí
Monitor both INR and phenytoin levels frequently when initiating, adjusting, or stopping either drug. Consider alternative anticonvulsants.