BMJ  2003;327:1454 (20 December), doi:10.1136/bmj.327.7429.1454

Ward round

Drug point

Possible interaction between warfarin and cranberry juice

¹ Pharmacovigilance Risk Assessment Unit, Medicines and Healthcare Products Regulatory Agency, London SW8 5NQ, ² Department of Pharmacology, University of Liverpool, Liverpool L69 3GE

After a chest infection (treated with cefalexin), a man in his 70s had a poor appetite for two weeks and ate next to nothing, taking only cranberry juice as well as his regular drugs (digoxin, phenytoin, and warfarin). Six weeks after starting cranberry juice he had been admitted to hospital with an INR (international normalised ratio) > 50. Before, his control of INR had been stable. He died of a gastrointestinal and pericardial haemorrhage. He had not taken any over the counter preparations or herbal medicines, and he had been taking his drugs correctly.

The Committee on Safety of Medicines has received seven other reports through the yellow card reporting scheme about a possible interaction between warfarin and cranberry juice leading to changes in INR or bleeding. In four cases, the increase in INR or bleeding after patients had drunk cranberry juice was less dramatic. In two cases, INR was generally unstable, and in another case INR decreased. Limited information is available about whether patients complied with their treatment in these cases.

Cranberry juice (Vaccinium macrocarpon) is popular and is also used to prevent cystitis.¹ Interaction with warfarin is biologically plausible because cranberry juice contains antioxidants, including flavonoids, which are known to inhibit cytochrome P450 enzymes,² and warfarin is predominantly metabolised by P450 CYP2C9.³ The constituents of different brands of cranberry juice may vary, and this might affect their potential for interacting with drugs. Whether the constituents of cranberry juice inhibit CYP2C9 and therefore the metabolism of warfarin or interact in another way needs further investigation. Until then, patients taking warfarin would be prudent to limit their intake of this drink.

---

Funding: None.

Competing interests: None declared.

References

1. Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M, Uhari M. Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women. BMJ 2001;322: 1571.[Abstract/Free Full Text]
2. Hodek P, Trefil P, Stiborova M. Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact 2002;139: 1-21.[CrossRef][ISI][Medline]
3. Rettie AE, Korzekwa KR, Kunze KL, Lawrence RF, Eddy AC, Aoyama T, et al. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chem Res Toxicol 1992;5: 54-9.[CrossRef][ISI][Medline]

(Accepted November 13, 2003)

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Pham, D. Q., Pham, A. Q. (2007). Interaction potential between cranberry juice and warfarin. Am J Health Syst Pharm 64: 490-494 [Abstract] [Full text]  
• Nagata, M., Hidaka, M., Sekiya, H., Kawano, Y., Yamasaki, K., Okumura, M., Arimori, K. (2007). Effects of Pomegranate Juice on Human Cytochrome P450 2C9 and Tolbutamide Pharmacokinetics in Rats. Drug Metab. Dispos. 35: 302-305 [Abstract] [Full text]  
• Chock, A. W. Y., Stading, J. A. (2006). Indeterminable International Normalized Ratio with concurrent use of warfarin and gatifloxacin.. Am J Health Syst Pharm 63: 1539-1542 [Full text]  
• Holbrook, A. M., Pereira, J. A., Labiris, R., McDonald, H., Douketis, J. D., Crowther, M., Wells, P. S. (2005). Systematic Overview of Warfarin and Its Drug and Food Interactions. Arch Intern Med 165: 1095-1106 [Abstract] [Full text]  
• Greenblatt, D. J., von Moltke, L. L. (2005). Interaction of Warfarin With Drugs, Natural Substances, and Foods. J Clin Pharmacol 45: 127-132 [Abstract] [Full text]  
• Huang, S.-M., Lesko, L. J. (2004). Drug-Drug, Drug-Dietary Supplement, and Drug-Citrus Fruit and Other Food Interactions: What Have We Learned?. J Clin Pharmacol 44: 559-569 [Abstract] [Full text]  

Rapid Responses:

Read all Rapid Responses

Patient care - who cares?

Maggie Spirito Perkins
bmj.com, 3 Jan 2004 [Full text]

Interaction between Warfarin and Cranberry juice. Premature Conclusion?

Michael Makris, et al.
bmj.com, 9 Jan 2004 [Full text]

Cranberry Sauce

David H Bevan
bmj.com, 25 Jan 2004 [Full text]

cranberry and warfarin

David Eso
bmj.com, 21 Oct 2006 [Full text]