Cranberry - Warfarin Interaction

Interaction Details

Warfarin is classified as belonging to the following category: Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, cranberry might increase the levels and adverse effects of CYP2C9 substrates. However, research is conflicting.
There is contradictory evidence about the effect of cranberry on CYP2C9 enzymes. In vitro evidence suggests that flavonoids in cranberry inhibit CYP2C9 enzymes. However, clinical research shows that cranberry juice does not significantly affect the levels, metabolism, or elimination of the CYP2C9 substrates flurbiprofen or diclofenac. Also, in patients stabilized on warfarin, drinking cranberry juice 250 mL daily for 7 days does not significantly increase the anticoagulant activity of warfarin, a CYP2C9 substrate. Additional pharmacokinetic research shows that cranberry juice does not increase peak plasma concentrations or area under the concentration-time curve of warfarin.

Interaction Rating

Likelihood of Occurrence

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

References

• Anon. Possible interaction between warfarin and cranberry juice. Current Problems in Pharmacovigilance 2003;29:8.
• Greenblatt DJ, von Moltke LL, Perloff ES, et al. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther 2006;79:125-33.
• Hodek P, Trefil P, Stiborova M. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact 2002;139:1-21..
• Li Z, Seeram NP, Carpenter CL, et al. Cranberry does not affect prothrombin time in male subjects on warfarin. J Am Diet Assoc 2006;106:2057-61.
• Lilja JJ, Backman JT, Neuvonen PJ. Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam - probes of CYP2C9, CYP1A2 and CYP3A4. Clin Pharmacol The 2007:81:833-9.
• Ushijima K, Tsuruoka S, Tsuda H, Hasegawa G, Obi Y, Kaneda T, Takahashi M, Maekawa T, Sasaki T, Koshimizu TA, Fujimura A. Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects. Br J Clin Pharmaco

Interaction Details

Warfarin is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, cranberry might increase the levels and adverse effects of CYP3A4 substrates.
A case of upper back pain, rhabdomyolysis, and abnormal liver function has been reported for a patient taking atorvastatin, a CYP3A4 substrate, in combination with cranberry juice 16 ounces daily for 2 weeks. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice. Also, animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine, a CYP3A4 substrate, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Uesawa, Y. and Mohri, K. Effects of cranberry juice on nifedipine pharmacokinetics in rats. J Pharm Pharmacol 2006;58(8):1067-1072.
• Doad GJ, Kabange W. Cranberry juice, atorvastatin and back pain. J Med Assoc Ga 2014;103(1):14.

Interaction Details

Warfarin is classified as belonging to the following category: Warfarin (Coumadin)

Theoretically, cranberry might increase the levels and adverse effects of warfarin. However, research is conflicting.
There is contradictory evidence about the effect of cranberry juice on warfarin. Case reports have linked cranberry juice consumption to increases in the international normalized ratio (INR) in patients taking warfarin, resulting in severe spontaneous bleeding and excessive postoperative bleeding. Daily consumption of cranberry sauce for one week has also been linked to an increase in INR in one case report. In a small study in healthy young males, taking a high dose of 3 grams of cranberry juice concentrate capsules, equivalent to 57 grams of fruit daily, for 2 weeks produced a 30% increase in the area under the INR-time curve after a single 25-mg dose of warfarin. However, 3 very small clinical studies in patients stabilized on warfarin reported that cranberry juice 250 mL once or twice daily for 7 days (27% cranberry juice or pure cranberry juice) or 240 mL once daily for 14 days does not significantly increase INR or affect plasma warfarin levels. The reasons for these discrepant findings are unclear. It is possible that the form and dose of cranberry may play a role, as cranberry extracts and juices contain different constituents. Additionally, an in vitro study evaluating 5 different cranberry juices found varying effects, with only a cranberry concentrate, and not diluted cranberry juices, inhibiting CYP2C9. However, this concentrate did not inhibit CYP2C9 activity in humans.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Anon. Possible interaction between warfarin and cranberry juice. Current Problems in Pharmacovigilance 2003;29:8.
• Grant P. Warfarin and cranberry juice: An interaction? J Heart Valve Dis 2004;13:25-6.
• Suvarna R, Pirmohamed M, Henderson L. Possible interaction between warfarin and cranberry juice. BMJ 2003;327:1454.
• Li Z, Seeram NP, Carpenter CL, et al. Cranberry does not affect prothrombin time in male subjects on warfarin. J Am Diet Assoc 2006;106:2057-61.
• Mohammed Abdul MI, Jiang X, Williams KM, et al. Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects. Br J Pharmacol 2008;154:1691-700.
• Mergenhagen KA, Sherman O. Elevated International Normalized Ratio after concurrent ingestion of cranberry sauce and warfarin. Am J Health-Syst Pharm 2008;65:2113-6.
• Ansell J, McDonough M, Zhao Y, et al. The absence of an interaction between warfarin and cranberry juice: a randomized, double-blind trial. J Clin Pharmacol 2009;49:824-30.
• Haber SL, Cauthon KA, Raney EC. Cranberry and warfarin interaction: a case report and review of the literature. Consult Pharm 2012;27:58-65.
• Hamann GL, Campbell JD, George CM. Warfarin-cranberry juice interaction. Ann Pharmacother 2011;45:e17.
• Roberts D, Flanagan P. Case report: Cranberry juice and warfarin. Home Healthc Nurse 2011;29:92-7.
• Isele, H. [Fatal bleeding under warfarin plus cranberry juice. Is it due to salicylic acid?]. MMW.Fortschr.Med 3-11-2004;146(11):13.
• Sylvan, L. and Justice, N. P. Possible interaction between warfarin and cranberry juice. Am Fam.Physician 9-15-2005;72(6):1000.
• Niklasson, A. and Andren, L. [Interaction between Waran and cranberry juice]. Lakartidningen 3-15-2006;103(11):853-854.
• Rindone, J. P. and Murphy, T. W. Warfarin-cranberry juice interaction resulting in profound hypoprothrombinemia and bleeding. Am J Ther 2006;13(3):283-284.
• Griffiths AP, Beddall A, Pegler S. Fatal haemopericardium and gastrointestinal haemorrhage due to possible interaction of cranberry juice with warfarin. J R Soc Promot Health 2008;128(6):324-6.
• Mellen CK, Ford M, Rindone JP. Effect of high-dose cranberry juice on the pharmacodynamics of warfarin in patients. Br J Clin Pharmacol 2010;70(1):139-42.
• Ngo N, Brantley SJ, Carrizosa DR, et al. The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation. J Exp Pharmacol. 2010;2010(2):83-91.

Warfarin Overview

• Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.

Cranberry - More Interactions

Cranberry interacts with 691 drugs

Interaction Rating Key

These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.