FAQ
Potential interaction between warfarin and cranberry juice: updated data
The Joint Commission’s National Patient Safety Goals (NPSG) 2008 include a goal for reducing harm associated with anticoagulation therapy (Goal 3E). Implementation expectations for this NPSG involve screening food/drug interactions with warfarin.
A series of case reports beginning in 2003 suggested the potential for cranberry juice to interact with warfarin, resulting in elevated international normalized ratio (INR) and hemorrhage. Most of the cases involved patients who ingested large amounts of cranberry juice and had other confounding factors such as lack of dietary intake. Nevertheless, an interaction was suspected and the warfarin labeling cautions patients to avoid cranberry juice and cranberry products.
The quality of evidence has improved with the publication of several clinical trials to further investigate the potential interaction between warfarin and cranberry juice. These trials are summarized in the table below.
Table. Summary of cranberry warfarin interaction literature.
Reference/methods |
Subjects |
Intervention |
Outcomes |
Results/Conclusions |
| Ansell 2007 R, DB, PC | n=30 with stable warfarin anticoagulation for various indications; stable was defined as INR between 1.7 and 3.3 for 2 readings within 8 weeks prior to the study. | Placebo (n=16) or cranberry juice (n=14) 8 ounces every day for 2 weeks | Any INR outside of the therapeutic range | On day 11, the cranberry juice recipients had a higher INR compared to the placebo group (p<0.02); however, overall mean INRs were similar at other time points and at the end of intervention. Conclusion: 8 ounces of cranberry juice daily does not seem to have a significant effect on INR. |
| Lilja 2007 Methods not specified | n=10 healthy volunteers | 200 mL cranberry juice three times daily for 10 days or water Warfarin 10 mg as a single dose on day 5 (tizanidine and midazolam were also investigated in this paper) | Pharmacokinetics of warfarin including concentration, time to maximum concentration, and half-life. | No significant differences were found in the pharmacokinetics of R-warfarin based on ingestion of cranberry juice; however, the elimination of S-warfarin was shortened (p<0.05). Conclusion: the authors concluded that there was no significant pharmacokinetic interaction between cranberry juice and warfarin. |
| Li 2006 R, DB, PC, XO | n=7 with atrial fibrillation on a stable dose of warfarin for 3 months prior to enrollment | Cranberry juice 250 mL per day x 7 days followed by placebo or vice versa (with a 7 day washout period) | INR measured at baseline and days 2, 4, 7, 10, 14, 16, 18, 21, and 24 | No significant difference was found between therapies in terms of INR at day 7 (2.23 for the cranberry group vs. 2.16 for the placebo group). Conclusion: No interaction was found with warfarin and 250 mL of cranberry juice per day. |
Summary
Recent randomized, controlled trials seem to refute a potential interaction between warfarin and cranberry juice (240 to 600 mL per day); however, it remains unclear if larger amounts of juice could lead to destabilization of warfarin therapy. In light of the updated evidence, it seems reasonable to allow patients taking warfarin to consume 1 glass (8 ounces or 240 mL) of cranberry juice daily; however, patients should still be warned about the potential interaction, especially if intake of cranberry juice increases.
References
The Joint Commission. 2008 National Patient Safety Goals Hospital Program. Available at: http://www.jointcommission.org/PatientSafety/NationalPatientSafetyGoals/08_hap_npsgs.htm. Accessed December 31, 2007.
Aston JL, Lodolce AE, Shapiro NL. Interaction between warfarin and cranberry juice. Pharmacotherapy 2006;26:1314-9.
Coumadin [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2007.
Ansell J, McDonough M, Harmatz JS, Greenblatt DJ. A randomized, double-blind trial of the interaction between cranberry juice and warfarin. J Thromb Thrombolysis 2007. Doi10.1007/s11239-007-0120-y.
Li Z, Seeram NP, Carpenter CL, Thames G, Minutti C, Bowerman S. Cranberry juice does not affect prothrombin time in male subjects on warfarin. J Am Diet Assoc 2006;106:2057-61.
Lija 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 Ther 2007;81:833-9.