Major
Established
설명
Tamoxifen dramatically increases warfarin anticoagulation, causing large INR elevations and a substantially elevated risk of serious bleeding.
기전
Tamoxifen and its metabolites inhibit CYP2C9, markedly reducing S-warfarin clearance; the effect on CYP3A4 further reduces R-warfarin clearance.
임상적 중요성
S-warfarin AUC may increase by >100%; major hemorrhage including intracranial bleeding has been documented. This is one of the most potent warfarin interactions.
관리 방법
Reduce warfarin dose by 30–50% when initiating tamoxifen; monitor INR very frequently (every 3–7 days) until stable. Consider alternative anticoagulants.