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