Warfarin acts by antagonizing the cofactor function of vitamin K. Variability in the anticoagulant response to warfarin is an ongoing clinical dilemma. Although clinical efficacy of warfarin varies with intake of vitamin K, genetic polymorphisms that modulate expression of CYP2C9, the isoform mediating clearance of S-warfarin, may have significant effect on warfarin therapy. Moreover, several herbal remedies also interact with warfarin. St. John's wort may have the potential to diminish warfarin's anticoagulation effect by increasing clearance through inducing CYP2C9 (66). Another report indicates that St. John's wort increases clearance of both R- and S-warfarin but ginseng has no effect (67).
Anticoagulant effect of warfarin increases if combined with coumarin-containing herbal remedies such as bilba, fenugreek and dong quai or with antiplatelet herbs such as danshen, garlic and ginkgo biloba. Conversely, vitamin K-containing supplement such as green tea may antagonize the anticoagulant effect of warfarin. The international normalization ratio (INR) was increased in a patient treated with warfarin for atrial fibrillation when he started taking coumarin-containing herbal products boldo and fenugreek. After discontinuation of herbal supplements, his INR returned to normal after 1 week (68,69). Increased anticoagulation due to interaction between warfarin and danshen has been reported. (70,71). Two cases of increased INR were mentioned in patients taking garlic previously stabilized on warfarin (72). A likely mechanism is an additive effect because garlic has antiplatelet activity.
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