Warfarin-Cranberry Juice Interaction Resulting in Profound Hypoprothrombinemia and Bleeding

Rindone, Joseph P.; Murphy, Terry

doi:10.1097/01.mjt.0000178908.32892.2f

Cited by 59 publications

(57 citation statements)

References 2 publications

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“…Recent studies have shown that cranberry juice potently inhibits CYP3A and CYP2C9 in vitro (9, 34); however, in vivo studies with probe substrates for CYP2C9 (S-warfarin), (20). Despite the lack of an effect of cranberry juice on the pharmacokinetics of warfarin (20), several case reports have indicated that cranberry juice results in an enhanced antithrombotic effect of warfarin (8,12,23,27,32,33), suggesting a possible pharmacodynamic effect. A number of studies have reported incidences of apple-, orange-, and grapefruit-drug interactions (6,7,21,29).…”

Section: Discussionmentioning

confidence: 99%

Effects of Cranberry Juice on Pharmacokinetics of β-Lactam Antibiotics following Oral Administration

Li¹,

Andrew

Wang³

et al. 2009

Antimicrob Agents Chemother

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Cranberry juice consumption is often recommended along with low-dose oral antibiotics for prophylaxis for recurrent urinary tract infection (UTI). Because multiple membrane transporters are involved in the intestinal absorption and renal excretion of ␤-lactam antibiotics, we evaluated the potential risk of pharmacokinetic interactions between cranberry juice and the ␤-lactams amoxicillin (amoxicilline) and cefaclor. The amoxicillin-cranberry juice interaction was investigated in 18 healthy women who received on four separate occasions a single oral test dose of amoxicillin at 500 mg and 2 g with or without cranberry juice cocktail (8 oz) according to a crossover design. A parallel cefaclor-cranberry juice interaction study was also conducted in which 500 mg cefaclor was administered with or without cranberry juice cocktail (12 oz). Data were analyzed by noncompartmental methods and nonlinear mixed-effects compartmental modeling. We conclude that the concurrent use of cranberry juice has no significant effect on the extent of oral absorption or the renal clearance of amoxicillin and cefaclor. However, delays in the absorption of amoxicillin and cefaclor were observed. These results suggest that the use of cranberry juice at usual quantities as prophylaxis for UTI is not likely to alter the pharmacokinetics of these two oral antibiotics.

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Section: Discussionmentioning

confidence: 99%

Effects of Cranberry Juice on Pharmacokinetics of β-Lactam Antibiotics following Oral Administration

Li¹,

Andrew

Wang³

et al. 2009

Antimicrob Agents Chemother

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“…On the basis of multiple published cases (including 2 cases of fatal interaction) reporting increased international normalized ratio (INR) and haemorrhage [21,22,23,24,25,26,27,28,29,30,31], serious concerns have been raised regarding a possible interaction with the anticoagulant warfarin. However, these warnings may possibly be attributed to misleading conclusions [32].…”

Section: Clinical Interactions Between Herbs and Conventional Drugsmentioning

confidence: 99%

Interactions between Herbs and Conventional Drugs: Overview of the Clinical Data

2012

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This article provides an overview of the clinical evidence of interactions between herbal and conventional medicines. Herbs involved in drug interactions – or that have been evaluated in pharmacokinetic trials – are discussed in this review. While many of the interactions reported are of limited clinical significance and many herbal products (e.g. black cohosh, saw palmetto, echinacea, hawthorn and valerian) seem to expose patients to minor risk under conventional pharmacotherapy, a few herbs, notably St. John’s wort, may provoke adverse events sufficiently serious to endanger the patients’ health. Healthcare professionals should remain vigilant for potential interactions between herbal medicines and prescribed drugs, especially when drugs with a narrow therapeutic index are used.

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“…Regarding this issue, the interaction of foods and beverages with drugs should be taken into consideration in clinical practice. Recently, several case reports showed that patients on warfarin therapy suffered from a profound hypoprothrombinemia after the ingestion of cranberry juice（CrJ) 3,4) .…”

Section: Introductionmentioning

confidence: 99%

The Inhibitory Effect of Cranberry Juice on Phenytoin Metabolism by Human Liver Microsomes

Ushijima

Koshimizu

Fujimura

2009

Jpn. J. Clin. Pharmacol. Ther.

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CYP2C9 is involved in the metabolism of many drugs such as warfarin and phenytoin（PHT). It is well known that some foods cause pharmacokinetic alterations of drugs and lead to toxicity. Regarding the interaction caused by cranberry juice（CrJ), its influence on the metabolism of warfarin, a CYP2C9 substrate, is controversial. In addition, information concerning the influence of CrJ on the pharmacokinetics of other substrate drugs of CYP2C9 is not available. To examine the inhibitory effect of CrJ on the metabolism of PHT, we performed experiments using a baculovirus expression microsome system and human liver microsome assay. CrJ concentration-dependently inhibited the substrate metabolism both in a baculovirus-expressed microsome system and in human liver microsome assay. These data support the idea that CrJ inhibits CYP2C9 activity, and the subsequent metabolism of drugs metabolized by CYP2C9. In this study, we did not identify the specific substance(s）which inhibits CYP2C9 activity. However, as CrJ did not enhance the PHT accumulation in 3D-HepG2 cells, it is thought that the penetration into hepatic cells of inhibitory substances in CrJ seems to be small.

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Warfarin-Cranberry Juice Interaction Resulting in Profound Hypoprothrombinemia and Bleeding

Cited by 59 publications

References 2 publications

Effects of Cranberry Juice on Pharmacokinetics of β-Lactam Antibiotics following Oral Administration

Effects of Cranberry Juice on Pharmacokinetics of β-Lactam Antibiotics following Oral Administration

Interactions between Herbs and Conventional Drugs: Overview of the Clinical Data

The Inhibitory Effect of Cranberry Juice on Phenytoin Metabolism by Human Liver Microsomes

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