Moderate
Probable
Description
Valproic acid can displace warfarin from plasma protein binding sites and may inhibit platelet aggregation, increasing bleeding risk.
Mechanism
Valproic acid displaces warfarin from albumin binding, transiently raising free warfarin concentrations; it also inhibits platelet aggregation independently through uncertain mechanisms.
Clinical Significance
Total warfarin levels may appear unchanged while free fraction rises; bleeding risk is increased even without marked INR changes.
Management
Monitor INR and clinical signs of bleeding closely when combining; measure free warfarin levels if available. Adjust dose if INR changes.