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Ask Dr. Stephan Moll
These questions have been submitted by folks on the mailing list and answered by Dr. Moll, Director of the Thrombophilia Program at the Carolina Cardiovascular Biology Center, Department of Medicine, Division of Hematology-Oncology, UNC Chapel Hill (North Carolina, USA). Why am I doing this?
80. Cranberry juice, Grapefruit juice and warfarin (Coumadin®)
Last Updated: 10/5/2009
"I have heard that one should not drink cranberry juice while taking
Coumadin®. Is this true? If so, what is the connection between the two?"
It is currently not known whether cranberry juice interacts with Coumadin®, but it may. By inhibiting and slowing the breakdown of Coumadin®, cranberry juice potentially increases the INR in some people, thus further thinning the blood.
Grapefruit juice
Grapefruit juice likely has no influence on warfarin levels and the INR.
It is, therefore, fine to drink for patients on warfarin.1 However, there
is a story about grapefruit juice that is interesting, because it highlights
that there may be interactions between juices that we drink and medications
that we take. Grapefruit juice has been shown to inhibit a major enzyme
in the intestine (the CYP3A4 enzyme of the cytochrome P450 enzyme complex)
that breaks down certain medications. Grapefruit juice contains chemicals
called furanocoumarins that cause many of these interactions.2 Medications
sensitive to the effects of grapefruit juice include some immunosuppressants,
blood pressure lowering drugs, and cholesterol lowering drugs (e.g., the
“statins”). Drinking of grapefruit juice has been shown to increase
the levels of these drugs in some people, leading to potentially dangerous
drug levels. Recommendations have therefore been made to avoid drinking
grapefruit juice when taking drugs such as cyclosporine (Neoral®), felodipine
(Plendil®), sirolimus (Rapamune®), simvastatin (Zocor®), and
lovastatin (Mevacor®).3
Cranberry juice
Early single case reports suggested that there may be an effect of cranberry
juice on the INR in individuals taking warfarin.4-8. These reports prompted
the United Kingdom’s CSM (Committee on the Safety of Medicines) and
MHRA (Medicines and Healthcare Products Regulatory Agency) to advise the
public against taking warfarin with cranberry juice. The US FDA later approved
labeling changes that caution patients about consuming cranberry juice/products
while taking warfarin.9 Four controlled studies have indicated that there
is no clinically important interaction between cranberry juice, when consumed
in moderation, and warfarin.10-13 These studies and their results have been
summarized in recent publications.9,13,14 Thus, it seems fine to drink cranberry
juice (8 oz, or 240 mL, per day or less) if one is on warfarin..
References:
- 1. Sullivan DM et al. Grapefruit juice and the response to warfarin.
Am J Health Syst Pharm 1998;55:1581-1583.
- 2. Paine MF et al. A furanocoumarin-free grapefruit juice establishes furanocoumarins
as mediators of the grapefruit juice-felodipine interaction. Am J Clin Nutr
2006;83:1097-105.
- 3. Huang S-M and Lesko LJ. Drug-drug, drug-dietary supplement, and drug-citrus
fruit and other food interactions: what have we learned? J Clin Pharmacol
2004;44:559-569.
- 4. Committee on the Safety of Medicines and the Medicines and Healthcare
Products Regulatory Agency. Interaction between warfarin and cranberry juice:
new advice Curr Prob Pharmacovigilance 2004;30:10.
- 5. Suvarna R et al. Possible interaction between warfarin and cranberry
juice. BMJ 2003;327:1454.
- 6. Griffiths J et al. Suspected warfarin-cranberry juice interaction. Canadian
Adverse Reaction Newsletter 2004; 14:2.
- 7. Rindone JP et al. Warfarin-cranberry juice interaction resulting in profound
hypopropthrombinemia and bleeding. Amer J Therap 2005;13:283-284.
- 8. Welch JM et al. Probable elevation in INR from cranberry juice. J Pharm
Technol 2007;23:104-107.
- 9. Mergenhagen KA et al. Elevated International Normalized Ratio after concurrent
ingestion of cranberry sauce and warfarin Am J Health Syst Pharm 2008:65:2113-2116.
- 10. Paeng CH et al. Interaction between warfarin and cranberry juice. Clin
Ther 2007;29:1730-1735.
- 11. Lilja JJ et al. 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; 81:833-839.
- 12. Li Z et al. Cranberry does not affect prothrombin time in male subjects
on warfarin. J Am Diet Assoc 2006; 106:2057-61.
- 13. Ansell J et al. The absence of an interaction between warfarin and cranberry
juice: a randomized, double-blind trial. J Clin Pharmacol 2009; 49:824-830.
- 14. Mohammed Abdul MI et al. Pharmacodynamic interaction of warfarin with
cranberry but not with garlic in healthy subjects. Br J Pharmacol 2008;
154:1691-1700.
Comment
This Q/A was prepared in collaboration with Mary F. Paine, PhD, pharmacist in the Division of Pharmacotherapy, Eshelman School of Pharmacy, the University of North Carolina, Chapel Hill, NC.
The information contained on the this web site is provided for your general information only. I am not a doctor and I do not give medical advice or engage in the practice of medicine. I do not recommend any particular treatment/trial for individuals, and in all cases recommend that you consult your physician or local treatment center before pursuing any course of treatment. It is up to you, as a consumer to find out if these trials posted are something you want to participate in. I just post the information.