Warfarin Cranberry juice

Inhibit the metabolizing isoenzyme (CYP2C9) of warfarin (cranberry juice, dan shen, ginseng, lycium, soy/soya)... 

Rindone JP, Murphy TW. Warfarin-cranberry juice interaction resulting in Tofound hypOjM O-thrombinemia and bleeding. AmJ Ther(200 13,283-4. 

ANTICOAGULANTS-ORAL CRANBERRY JUICE Cases of markedly T anticoagulant effect (including fatal haemorrhage) with regular cranbeny juice ingestion Uncertain possibly due to inhibition of CYP-mediated metabolism of warfarin Patients taking warfarin should avoid cranberry juice... 

Cranberry juice has been reported to enhance the action of warfarin (276). 

The Committee on Safety of Medicines has received several other reports through the yellow card reporting scheme about a possible interaction between warfarin and cranberry juice. In one case, this effect was suggested to have been due to contamination with salicylic acid, which displaces warfarin from protein binding sites (278). 

Grant P. Warfarin and cranberry juice an interaction J Heart Valve Dis 2004 13(l) 25-6. 

Suvarna R, Pirmohamed M, Henderson L. Possible interaction between warfarin and cranberry juice. BMJ 2003 327(7429) 1454. 

Preiselbeersaft. Liegt s an der Salizylsaure [Fatal bleeding under warfarin plus cranberry juice. Is it due to salicylic acid ] MMW Fortschr Med... 

The Committee on Safety of Medicines has received several other reports through the yellow card-reporting scheme about a possible interaction between warfarin and cranberry juice. 

It appears that cranberry juice may be effective in preventing the recurrence of urinary tract infections, but not in treating urinary tract infections. It is generally well tolerated and relatively free of adverse effects. There have been case reports of coadministration of cranberry juice and warfarin resulting in bleeding events, but this potential interaction remains to be conclusively established. 

A number of case reports surest that cranberry juice can increase the HSR of patients taking warfarin, and one patient has died as a result of this interaction. Limited evidence su ests that the use of cranberiy juice in patients taking warfarin can result in unstable HSRs, or, in one isolated case, a reduced HSR. 

In a further case, a patient stabilised on warfarin was found to have INRs of 10 to 12 in the days prior to a surgical procedure, although he had no previous record of an INR greater than 4. Vitamin K was given, and heparin was substituted for warfarin. When warfarin was restarted post-operatively, the INR quickly rose to 8 and then to 11 with haematuria, and postoperative bleeding. The patient was drinking almost 2 litres of cranberry juice daily, because of recurrent urinary tract infections, and was advised to stop drinking this. After three days the INR had stabilised at 3. 

In October 2004, the MHRA/CSM in the UK noted that they had now received 12 reports of a suspected interaction. These included 5 additional cases of bleeding episodes and two additional cases of unstable INRs in patients drinking cranberry juice while taking warfarin. 

The incidence and general clinical importance of this interaction is unknown, but the current recommendation of the CSM/MHRA in the UK is that patients taking warfarin should avoid drinking cranberry juice unless the health benefits are considered to outweigh any risks. They recommend increased INR monitoring for any patient taking warfarin and a regular intake of cranberry juice. They also advise similar precautions with other cranberry products (such as capsules or concentrates). Further study is needed. 

Committee on Safety of Medicines/Medicines and Healthcare products R ttlatory ency. Interaction between warfarin and cranberry juice new advice. Current Problems (2004) 30,... 

None of these interactions is very well documented, and their clinical relevance is unclear. Note that vitamin K in food commonly interacts with warfarin, and these interactions are discussed in Coumarins and related drugs + Foods Vitamin Kj-rich , p.409. See also cranberry juice , (p.398), enteral and parenteral nutrition , (below), grapefruit juice , (p.411), mango , (p.408) and soya bean products , (p.408). 

Although several case reports have indicated a concern for a potential interaction between cranberry juice and warfarin (CSM 2003 Grant 2004 Rindone and Murphy 2006 Suvarna et al. 2003), human clinical trials have indicated no interaction at amounts up to 480 ml ( 2 cups) daily (Ansell et al. 2009 Li et al. 2006 Lilja et al. 2007 Mellen et al. 2010). A review of clinical trials and published and unpublished case reports indicated that there is limited evidence to support an interaction between cranberry juice and warfarin (Zkria et al. 2010). A study with cranberry juice concentrate indicated a possible interaction with warfarin (Abdul et al. 2008). 

In a study of cranberry juice (200 ml daily) and warfarin in healthy volunteers, no clinically significant effects of cranberry juice on warfarin metabolism were observed after 10 days of treatment (Lilja et al. 2007). 

Increased INR was observed in healthy volunteers orally administered 1000 mg cranberry juice concentrate (equivalent to 57 g of cranberries) daily, before or after single doses of 25 mg warfarin. Plasma levels of warfarin were unchanged (Abdul et al. 2008). 

In a systematic review of interactions between warfarin and selected foods, the interaction potential for cranberry was ranked as "possible" on a scale that included the rankings of "highly probable, probable, possible, and highly improbable" (Holbrook et al. 2005). A review of case reports and clinical trial data on the potential interaction between cranberry and warfarin concluded that the available information does not support a clinically relevant interaction, but that patients taking warfarin should be cautioned about the potential interaction (Pham and Pham 2007). A third review on cranberry and warfarin suggested that large amounts of cranberry juice may adversely affect patients on warfarin, while small amounts of juice are not expected to cause an interaction (Aston et al. 2006). 

Abdul, M.I.M., X. Jiang, K.M. Williams, et al. 2008. Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects. Bn /. Pharmacol. 154(8) 1691. Ansell, J., M. McDonough, Y. Zhao, J.S. Harmatz, and D.J. Greenblatt. 2009. The absence of an interaction between warfarin and cranberry juice A randomized, double-blind trial. /. Clin. Pharmacol. 49(7) 824. 

Aston, J.L., A.E. Lodolce, and N.L. Shapiro. 2006. Interaction between warfarin and cranberry juice. Pharmacotherajn/ 26(9) 1314-1319. 

Grant, P. 2004. Warfarin and cranberry juice An interaction /. Heart Valve Dis. 13(l) 25-26. 

Griffiths, A.P, A. Beddall, and S. Pegler. 2008. Fatal haemopericar-dium and gastrointestinal haemorrhage due to possible interaction of cranberry juice with warfarin. J. Roy. Soc. Prom. Health 128(6) 324-326. 

LUja, J.J., J.T. Backman, and P.J. Neuvonen. 2007. Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam—Probes of CYP2C9, CYP1A2, and CYP3A4. Clin. Pharmacol. Ther. 81(6) 833-839. 

Mellen, C.K., M. Ford, and J.R Rindone. 2010. Effect of high dose cranberry juice on the pharmacodynamics of warfarin in patients. Br. J. Clin. Pharmacol. 70(1) 139-142. 

Pham, D.Q., and A.Q. Pham. 2007. Interaction potential between cranberry juice and warfarin. Am.. Health Syst. Pharm. 64(5) 490-494. 

Another case of increased anticoagulation in a patient taking warfarin and cranberry juice has been reported, with fatal internal hemorrhage in an elderly man [56 ]. 

However, despite anecdotal reports, small formal studies have failed to show any interaction of warfarin with cranberry juice. In 30 patients taking warfarin with stable INRs of 1.7-3.3, who were randomized to 240 ml of cranberry juice or a placebo beverage, matched for color and taste, once daily for 2 weeks, cranberry juice had no effect on plasma S- or R-war-farin plasma concentrations, and there were only minimal changes in INR on one day during the study [57. However, a study of this size does not rule out an effect in a susceptible subpopulation, and a larger case-control study may be the only way to settle the apparent discrepancy between formal studies and anecdotal reports. 

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