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Red and Potentially Red/Purple? Cranberry Juice and Warfarin
By Russell H. Greenfield, MD, Dr. Greenfield is Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC, and Visiting Assistant Professor, University of Arizona, College of Medicine, Tucson, AZ; he reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.
Source: Pham DQ, et al. Interaction potential between cranberry juice and warfarin. Am J Health-Syst Pharm 2007;64:490-494.
Abstract: Readers of Alternative Therapies in Women's Health will recall that grapefruit and Seville orange juice both inhibit cytochrome P-450 isoenzyme 3A (CYP3A), potentially raising serum levels of medications that are metabolized through CYP3A. More recently, reports of interaction between cranberry juice and warfarin have come to light. Warfarin is metabolized in part through CYP2C9, and concerns have been raised that cranberry juice may inhibit this enzyme. The authors of this study conducted a literature review of the topic to assess requisite level of concern regarding the use of cranberry juice.
Articles published in English were retrieved after a search of Medline, Embase, International Pharmaceutical Abstracts, and IDIS. A sum total of but three case reports (each involving an elderly patient, two of whom ingested very large quantities of cranberry juice daily) and two randomized, placebo-controlled trials were identified. In only one of the case reports was strong evidence of a causal effect of cranberry juice on a rising INR present. A randomized crossover trial assessed the effect of a number of beverages, including cranberry juice, on CYP2C9 activity (via effects on flurbiprofen) and showed no significant impact. The other trial, an open-label, randomized crossover study addressed the effect of cranberry juice on CYP3A, not CYP2C9, but likewise found no significant interaction.
As an addendum, the authors note that a recent small randomized, placebo-controlled trial of men with atrial fibrillation receiving warfarin showed that 250 mL of cranberry juice enjoyed daily for seven days had no significant effect on INR. The authors conclude that there are few data to suggest a meaningful interaction between cranberry juice and warfarin, but that patients should be apprised of a potential reason for caution.
Cranberry juice is tasty and gained popularity when data accumulated that drinking it may help protect against urinary tract infections (by preventing bacterial adherence to the mucosal lining of the genitourinary tract). On the other hand, warfarin is the most commonly used oral anticoagulant agent. Reports of complications associated with the combination of cranberry juice and warfarin reached the attention of The United Kingdom's Committee on Safety of Medicines, and a warning to health care practitioners ensued. The warning was prudent, but also appears to be premature. A significant number of factors can impact warfarin activity, including dietary changes (low intake of vitamin K), infection (cytokine release), and drug interactions (fluconazole, isoniazid, and lovastatin all inhibit CYP2C9). The case for adverse interaction between cranberry juice and warfarin appears to be weak. For patients on warfarin whose INR results are increasing, a query into their use of cranberry juice may be a good idea. Advice against drinking cranberry juice while taking warfarin, however, appears to be unwarranted.