説明
Levothyroxine enhances the catabolism of vitamin K-dependent clotting factors, amplifying warfarin's anticoagulant effect and raising the risk of bleeding when thyroid replacement is initiated or doses are increased.
機序
Thyroid hormone accelerates the hepatic catabolism of vitamin K-dependent coagulation factors (II, VII, IX, X); as circulating factor levels fall, warfarin's anticoagulant effect is potentiated, resulting in INR elevation.
臨床的意義
Well-documented pharmacodynamic interaction; INR may increase by 20–50% when levothyroxine is initiated or dose-escalated in patients on stable warfarin therapy.
対処法
Monitor INR within 4–6 weeks of starting or adjusting levothyroxine; reduce warfarin dose prophylactically by 10–25% when initiating thyroid replacement; increase monitoring until INR is stable.