Major
Established
Description
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.
Mécanisme
Acute phenytoin administration inhibits CYP2C9; with chronic use, CYP2C9 induction predominates, increasing warfarin clearance. Warfarin may displace phenytoin from albumin and inhibit its metabolism.
Signification clinique
Both bleeding (early) and thromboembolic (late) events have occurred; warfarin can also raise phenytoin levels, risking phenytoin toxicity.
Prise en charge
Monitor both INR and phenytoin levels frequently when initiating, adjusting, or stopping either drug. Consider alternative anticonvulsants.