Interaction Between Warfarin and Cranberry Juice

Jonathan L. Aston, BS; Amy E. Lodolce, PharmD; and Nancy L. Shapiro, PharmD

Disclosures

Pharmacotherapy. 2006;26(9):1314-1319. 

In This Article

Abstract and Introduction

Abstract

Warfarin is extensively used for anticoagulation to a target international normalized ratio of 2.0-3.0 for most indications or 2.5-3.5 for high-risk indications; however, many drugs and dietary supplements induce fluctuations in the international normalized ratio. Such fluctuations may lead to therapeutic failure or bleeding complications. Cranberry juice is increasingly used for the prevention and adjunctive treatment of urinary tract infections. The United Kingdom's Committee on Safety of Medicines has alerted clinicians to a potential interaction between warfarin and cranberry juice and has advised that patients avoid their concurrent use. Review and analysis of the literature revealed that ingestion of large volumes of cranberry juice destabilize warfarin therapy. Small amounts of juice are not expected to cause such an interaction. Clinicians should be aware of this potential interaction and monitor and counsel patients accordingly.

Introduction

Since its discovery in the early 1940s, warfarin has become the most extensively used anticoagulant drug.[1] Warfarin is indicated for the treatment and prophylaxis of thromboembolic events associated with myocardial infarction, atrial fibrillation, prosthetic valve replacement, deep vein thrombosis, and pulmonary embolism. Its mechanism of action involves inhibiting the activation of vitamin K-dependent clotting factors II, VII, IX, and X. Anticoagulation with warfarin is often difficult to manage and stabilize because of interpatient variability, the high degree of protein binding, its narrow therapeutic index, and its penchant for drug and food interactions.[1,2] The target international normalized ratio (INR) is 2.0-3.0 for most indications and 2.5-3.5 for high-risk indications.

Many drugs induce fluctuations in the INR by inhibiting or inducing the metabolism of warfarin and by competing with albumin-binding sites. In addition, concomitant use of antithrombotic, antiplatelet, or nonsteroidal antiinflammatory drugs can potentiate the risk of bleeding in patients taking warfarin. Alterations in dietary intake of vitamin K and consumption of alcohol can elicit instability in anticoagulation management.[2] Such variations can lead to therapeutic failure, resulting in thromboembolism or bleeding complications.[1] Given the capricious nature of warfarin, extensive patient education, continuous monitoring, and identification of impending sources of variability are needed to achieve safe and effective anti-coagulation. Several case reports have implicated cranberry juice as another potential substance that interacts with warfarin.[3,4,5,6,7] The prescribing information for warfarin was updated in September 2005 to include cranberry products as a potential herb that may increase the effects of warfarin.[2]

Cranberries, a fruit native to North America, are primarily cultivated for consumption as foods and beverages.[8] The juice and concentrated extract from cranberries are increasingly used for the prevention and adjunctive treatment of urinary tract infections.[8,9] Cranberry fruit is also used in alternative medicine as an antipyretic and a urinary deodorizer in patients with incontinence. The bacteriostatic mechanism of cranberries was initially attributed to the acidification of urine due to increased urinary concentration of hippuric acid. However, data now suggest that several high-molecular-weight components of cranberry juice, including proanthocyanidin, decrease virulence by disrupting the adhesion of bacterial fimbriae to glycolipids in the endothelial layer of the genitourinary tract. Cranberry juice seems to be most effective in preventing the adhesion of Escherichia coli and Enterococcus faecalis, which are responsible for more than 85% of urinary tract infections.[10]

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