Updates on the clinical evidenced herb-warfarin interactions.

Beikang Ge,Zhen Zhang,Zhong Zuo

doi:10.1155/2014/957362

Abstract

Increasing and inadvertent use of herbs makes herb-drug interactions a focus of research. Concomitant use of warfarin, a highly efficacious oral anticoagulant, and herbs causes major safety concerns due to the narrow therapeutic window of warfarin. This paper presents an update overview of clinical findings regarding herb-warfarin interaction, highlighting clinical outcomes, severity of documented interactions, and quality of clinical evidence. Among thirty-eight herbs, Cannabis, Chamomile, Cranberry, Garlic, Ginkgo, Grapefruit, Lycium, Red clover, and St. John's wort were evaluated to have major severity interaction with warfarin. Herbs were also classified on account of the likelihood of their supporting evidences for interaction. Four herbs were considered as highly probable to interact with warfarin (level I), three were estimated as probable (level II), and ten and twenty-one were possible (level III) and doubtful (level IV), respectively. The general mechanism of herb-warfarin interaction almost remains unknown, yet several pharmacokinetic and pharmacodynamic factors were estimated to influence the effectiveness of warfarin. Based on limited literature and information reported, we identified corresponding mechanisms of interactions for a small amount of “interacting herbs.” In summary, herb-warfarin interaction, especially the clinical effects of herbs on warfarin therapy should be further investigated through multicenter studies with larger sample sizes.

Highlights

Warfarin has been the most commonly used oral anticoagulants ever since its approval in 1954 [1]
On basis of what have been done on herb-warfarin interactions, the current review aims at complementing the missing points from previous studies as summarized below: (i) classification of clinical significance: life threaten, bleeding, INR change, and so forth; (ii) assessment of evidence reliabilities: highly probable, probable, possible, and doubtful; (iii) classification of evidence level: in vitro, animal, or human; (iv) summary and classifications of mechanisms for herbwarfarin interactions: pharmacokinetics or pharmacodynamics; (v) information related to interactions between traditional Chinese medicines (TCM) and warfarin
Thirty-eight herbs were listed in the current review, including herbs clinically evidenced to interact with warfarin; herbs preclinical evidenced to affect PK or PD of warfarin; herbs containing vitamin K or coumarin; and herbs with similar or opposite pharmacological actions to those of warfarin

Summary

Introduction

Warfarin has been the most commonly used oral anticoagulants ever since its approval in 1954 [1]. S-warfarin is 3–5 times more potent than Renantiomer in anticoagulation effects. The anticoagulation effects are currently believed to be due to warfarin interrupting the vitamin K cycle in liver: in coagulation cascade, activated clotting factors are indispensable for the formation of blood clot. Most of these clotting factors are vitamin K dependent proteins, which suggest that reduced vitamin K is essential for activating clotting factors. Since vitamin K epoxide reductase (VKOR) is responsible for the synthesis of reduced vitamin K, warfarin, by targeting at and inhibiting VKOR, can block the activation of clotting factors and decrease the blood clot [3]

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Conclusion