Probable Elevation in International Normalized Ratio from Cranberry Juice

Welch, Justin M.; Forster, Keith

doi:10.1177/875512250702300207

Cited by 16 publications

(9 citation statements)

References 13 publications

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“…The US Food and Drug Administration (FDA) agreed with MHRA/CSM and in 2006, advised manufactures of warfarin to update the package insert with the warning. The majority of evidence documenting the interaction is from case reports [86][87][88][89][90][91], however a study was published in 2006 investigating a possible mechanism for the interaction [92]. The authors suggested the cranberry flavonoid may alter the biosynthesis of CYP isoenzymes, especially CYP2C9, which would affect the metabolism of S-warfarin.…”

Section: Cranberry Juicementioning

confidence: 97%

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

Nutescu

Chuatrisorn

Hellenbart

2011

J Thromb Thrombolysis

224

153

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Clinicians and patients around the world have been intrigued by the concept of developing an oral anticoagulant with a broad therapeutic window and few drug and dietary interactions that can be administered at fixed doses with no or minimal monitoring. The recently approved oral direct thrombin inhibitor dabigatran, along with the emerging oral anti-factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, have been developed to address many of the shortcomings of warfarin therapy. As warfarin is associated with extensive food and drug interactions, there is also a need to consider such interactions with the new oral anticoagulants. While to date few drug and dietary interactions have been reported with the new oral anticoagulants, it is still early in their development and clinical use cycle. Pharmacokinetic and pharmacodynamic profiles will have to be closely accounted for when determining the likelihood of a potential drug interaction prior to therapy initiation. As the list of drugs and supplements that interact with warfarin is continuously expanding, and the knowledge on drug interactions with the novel oral anticoagulants is still in its infancy, clinicians need to be vigilant when initiating any of these agents or when any changes in the patient's medication profile occur and perform a close screening for potential drug and dietary interactions. The objective of this paper is to give an update on drug and dietary interactions with warfarin and the novel oral anticoagulants, dabigatran, rivaroxaban, apixaban, and edoxaban.

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Section: Cranberry Juicementioning

confidence: 97%

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

Nutescu

Chuatrisorn

Hellenbart

2011

J Thromb Thrombolysis

224

153

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“…96e99 Nonetheless, an interaction with warfarin cannot be ruled out, particularly when large volumes of cranberry juice are drunk regularly, or when cranberry products other than juice are taken. 96,97,100 Thus, the INR should be monitored more closely in patients on warfarin if they consume large amounts of cranberry juice or take other cranberry supplements for prophylaxis against UTIs. 96 Quantifying the effects of CYP450 inhibition and induction Quantification of the effects of CYP450 inhibitors and inducers is still evolving.…”

Section: Cyp450 Drugefood Interactionsmentioning

confidence: 99%

Variability in Response to Drugs

Twycross

Ross

Kotlińska-Lemieszek

et al. 2015

Journal of Pain and Symptom Management

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There is great inter-individual variability in the way people respond to a drug (Box A). Some of this variability is predictable in the presence of clinical factors known to impact upon the pharmacokinetics and/or pharmacodynamics of a drug. For example, an age-related decrease in overall metabolic capacity of the liver, because of reductions in liver mass, liver enzyme activity and hepatic blood flow, results in the elderly being at a significantly higher risk of toxicity from drugs metabolized in the liver. Similarly, an age-related decline in renal function can reduce the excretion of active drugs and metabolites, e.g., morphine-6-glucuronide and morphine-3-glucuronide, increasing the risk of toxicity from morphine.Genetic variations also contribute towards differences in drug response. Clinically, these are less predictable, although some may be detected with specific testing. They are particularly important for drugs metabolized by cytochrome P450 (CYP450) with the rate of metabolism either reduced or increased. Examples of how these manifest include: reduced or no response because of ➢ the failure to convert a pro-drug to its active form ➢ increased metabolism of an active drug to an inactive metabolite increased toxicity because of ➢ more rapid conversion to the active form or to a metabolite which is more active than the parent drug ➢ failure to metabolize an active drug to inactive metabolite(s). Other genetic variations, such as genes coding for receptors or drug transporters also can influence overall response, e.g., the m-opioid receptor or P-glycoprotein transporter and the response to opioids. Induction or inhibition of CYP450 activity also can result from a drugedrug or drugefood interaction causing similar manifestations to those resulting from genetic variation. Each of these factors is considered in more detail below.

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“…Interestingly, these clinical studies (21,25,27) used cranberry juice, unlike the Abdul et al (2008) study which used cranberry juice concentrate (26), raising speculation on the likely differences in the distribution of active principles between a cranberry concentrate vs juice. In this context, it is important to point out that several case reports have been published in the past several years that claim that ingestion of cranberry juice effects the INR and de-stabilizes the warfarin dose, necessitating a dose readjustment to obtain therapeutic anti-coagulant effect (38)(39)(40)(41)(42). In most of the instances, the acute consumption of cranberry juice was not deemed very high, with the exception of one or two instances where the patient drank almost 750 mL to 2 L of cranberry juice per day.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Cranberry Juice Ingestion and Clinical Drug-Drug Interaction Potentials; Review of Case Studies and Perspectives

Srinivas¹

2013

J Pharm Pharm Sci

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Cranberry juice is a popular beverage with many health benefits. It has anthocyanins to supplement dietary needs. Based on in vitro evidence cranberry juice is an inhibitor of CYP enzymes and at higher amounts as potent as ketoconazole (CYP3A) and fluconazole (CYP2C9). There is, however, a discrepancy between in vitro and in vivo observations with respect to a number of substrates (cyclosporine, warfarin, flurbiprofen, tizanidine, diclofenac, amoxicillin, ceflacor); with the exception of a single report on midazolam, where there was a moderate increase in the AUC of midazolam in subjects pre-treated with cranberry juice. However, another study questions the clinical relevancy of in vivo pharmacokinetic interaction between cranberry juice and midazolam. The controversy may be due to a) under in vitro conditions all anthocyanin principles may be available to have a concerted effort in CYP inhibition; however, limited anthocyanin principles may be bioavailable with varying low levels in the in vivo studies; b) a faster clearance of the active anthocyanin principles under in vivo conditions may occur, leading to low threshold levels for CYP inhibition; c) efficient protein binding and/or rapid tissue uptake of the substrate may have precluded the drug availability to the enzymes in the in vivo studies. With respect to pharmacodynamic aspects, while the debate continues on the issue of an interaction between warfarin and cranberry juice, the summation of the pharmacodynamics data obtained in patients and healthy subjects from different prospectively designed and controlled clinical trials does not provide overwhelming support for the existence of a pharmacodynamic drug interaction for normal cranberry juice ingestion. However, it is apparent that consumption of large quantities of cranberry juice (about 1-2 L per day) or cranberry juice concentrates in supplements for an extended time period (>3-4 weeks) may temporally alter the effect of warfarin. Therefore, the total avoidance of cranberry juice by warfarin users may not be warranted by the published studies. However, in certain situations of higher intake of cranberry juice or concentrate there may be a need to monitor both warfarin doses and its effect. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Probable Elevation in International Normalized Ratio from Cranberry Juice

Cited by 16 publications

References 13 publications

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

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

Variability in Response to Drugs

Cranberry Juice Ingestion and Clinical Drug-Drug Interaction Potentials; Review of Case Studies and Perspectives

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