Effect of high‐dose cranberry juice on the pharmacodynamics of warfarin in patients

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTCase reports suggest an association between cranberry juice and potentiation of warfarin. Studies using 240 ml of cranberry juice daily demonstrated no interaction. It is unknown if higher amounts of cranberry juice will interact with warfarin. WHAT THIS STUDY ADDSCranberry juice at 240 ml twice daily does not alter the pharmacodynamics of warfarin. AIMTo determine if high-dose cranberry juice (240 ml twice daily) alters the pharmacodynamic action of warfarin. METHODSTen male patients taking stable doses of warfarin were given cranberry juice at 240 ml twice daily for 7 days. Prothrombin times were drawn at baseline and days 2, 6 and 8 after administration of the juice. Prothrombin times were averaged for each day and mean times were compared from each study day to baseline using repeated measures ANOVA. RESULTSThere was no statistical difference between mean prothrombin time at baseline and any day tested during juice administration. CONCLUSIONSCranberry juice (240 ml twice daily for 1 week) did not alter the pharmacodynamics of warfarin in patients.

Warfarin-Cranberry Juice Interaction

“…Two of the prospective trials enrolled young, healthy volunteers, 22,26 while the others enrolled patients already taking warfarin who had additional comorbidities. 20,21, 23 An inherent limitation of this and other case reports is the reliance upon subjective information. In this case report no confounding factors were identified to explain the INR elevations, although that does not rule out their existence.…”

Pomegranate Juice and Pomegranate Extract Do Not Impair Oral Clearance of Flurbiprofen in Human Volunteers: Divergence From In Vitro Results

“…5, 33–35 However, a number of controlled studies in humans -- involving both human volunteers and patients receiving warfarin anticoagulation -- showed that customary doses of cranberry juice have minimal or no effect on the pharmacokinetics of S-warfarin and other CYP2C9 substrates, as well as minimal or no effect on warfarin anticoagulation. 28,33, 34, 36, 37 A realistic risk assessment, based on all available data, is that cranberry juice can be ingested by warfarin- treated patients with negligible hazard of excessive anticoagulation or bleeding due to a pharmacokinetic drug interaction. 35, 38 …”

Drug and dietary interactions of warfarin and novel oral anticoagulants: an update

“…Patients who were randomized to receive 240 ml of cranberry juice daily for 2 weeks showed no effect on INR. Most recently, a prospective open-labeled study gave ten patients taking warfarin 240 ml of cranberry juice twice daily for 1 week [95]. Again, no significant change in the mean prothrombin time (PT) was noted and no adverse events, including bleeding or bruising were reported.…”

“…However, it has also been suggested that cranberry juice may interact with warfarin via a VKORC1 genotype-dependent interaction [93]. The potential interaction remains controversial because following the precautionary statement issued by the FDA, three clinical trials were published documenting no significant interaction [94][95][96]. The first trial randomized seven patients with atrial fibrillation to consume 250 ml of cranberry juice while taking warfarin [96].…”