Systematic Overview of Warfarin and Its Drug and Food Interactions

Holbrook, Anne; Pereira, Jennifer A.; Labiris, Renée; McDonald, Helen; Douketis, James D.; Crowther, Mark; Wells, Philip S.

doi:10.1001/archinte.165.10.1095

Cited by 1,004 publications

(765 citation statements)

References 219 publications

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“…However, several patient dependent factors have been demonstrated to have impact upon warfarin's bioavailablity, for example diet, genetic disposition, age, pharmaceutical regime (Holbrook et al, 2005). An issue intimately related to the complexity of warfarin's bioavailability is its chameleon-like behaviour, whereby the relative concentrations of the ensemble of warfarin isomers present can be profoundly influenced by molecular environment (Karlsson et al, 2007(Karlsson et al, , 2009).…”

Section: Resultsmentioning

confidence: 99%

Warfarin: an environment‐dependent switchable molecular probe

Nicholls

Karlsson

Rosengren

et al. 2010

J of Molecular Recognition

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The complex nature of the structure of the anticoagulant warfarin is reflected in the diversity of binding modes observed in warfarin-protein recognition systems. A series of theoretical, 1 H-NMR and steady state and time resolved fluorescence spectroscopic studies, have been used to establish correlations between the molecular environment provided by various solvent systems and the relative concentrations of the various members of warfarin's ensemble of isomers. A consequence of these observations is that the judicious choice of solvent system or molecular environment of warfarin allows for manipulation of the position of the equilibrium between isomeric structures such as the hemiacetal and open phenol-keto forms, the latter even possible in a deprotonated form, where in each case unique spectroscopic properties are exhibited by the respective structures. Collectively, warfarin's capacity to adapt its structure as a function of environment in conjunction with the fluorescence behaviours of the various isomers together provide an environment-dependent molecular switch with reporter properties, which allows for the simultaneous detection of warfarin in different states with lifetimes spanning the range < 0.10-5.5 ns. These characteristics are here used to examine warfarin binding domains in a series of materials (solvents, protein, inorganic matrix and synthetic polymer). Moreover, these studies demonstrate the potential for using warfarin, or other switchable analogues thereof, as a tool for studying molecular level characteristics, for example local dielectricity.

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Section: Resultsmentioning

confidence: 99%

Warfarin: an environment‐dependent switchable molecular probe

Nicholls

Karlsson

Rosengren

et al. 2010

J of Molecular Recognition

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“…Perhaps the best described example of this phenomenon is testing for genetic variance in CYP2C9 and VKORC1 which have been shown to alter patients' response to Coumadin, a medication that is used by millions of people in the United States and is associated with a significant risk of bleeding. 9 An initial report by AEI-Brooking Joint Centre for Regulatory Studies suggested that testing for polymorphisms in these genes would decrease health care spending in the United States by up to two billion dollars annually. 10 This report, which was published before any clinical study had empirically demonstrated improved patient outcomes, has been subsequently followed by several studies that are more discouraging.…”

Section: Diagnostic and Drug Researchmentioning

confidence: 99%

Personalized Medicine: Understanding Probabilities and Managing Expectations

Laksman

Detsky

2010

J GEN INTERN MED

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Personalized medicine promises to represent a transformation in clinical care that will be ushered in by the unprecedented growth and development in the field of human genetics. Further examination of the scientific foundations of this new hope reveals a great number of challenges that lie ahead. While basic science research feverishly races to produce solutions, we continue to wait for the translation of deliverables. Products that have and will come to market may leave our clinical communities and systems exposed and unprepared. At each step, from basic science research to infrastructure development, a great deal of creativity and investment are required before the arsenal of more personalized tools can be assimilated into our current models of health care. This commentary seeks to share perspectives on the current status of personalized medicine from the vantage point of several potential investors, and integrate them into a common set of goals and understanding. We conclude that the stylized model of personalized medicine is more akin to a marketing tool than a literal prediction of the future.

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“…Its metabolism can be increased or decreased by numerous medications, foods, and alcohol, but the evidence to support the clinical consequences of these interactions is limited. 9 Warfarin co-administration with azole antibiotics, macrolides, quinolones, non-steroidal anti-inflammatory drugs, serotonin uptake inhibitors, lipid lowering agents, amiodarone, and fluoruracil should be done only with close monitoring. 9,10 From 0.4 to 2.0% of patients require transfusion, hospitalization, or surgery due to bleeding caused by warfarin toxicity.…”

Section: Risks and Side Effectsmentioning

confidence: 99%

“…9 Warfarin co-administration with azole antibiotics, macrolides, quinolones, non-steroidal anti-inflammatory drugs, serotonin uptake inhibitors, lipid lowering agents, amiodarone, and fluoruracil should be done only with close monitoring. 9,10 From 0.4 to 2.0% of patients require transfusion, hospitalization, or surgery due to bleeding caused by warfarin toxicity. This outcome is given as one of the most common reasons sited for the underutilization of warfarin anticoagulation.…”

Section: Risks and Side Effectsmentioning

confidence: 99%

Reversal of vitamin K antagonists prior to urgent surgery

Grobler

Callum

McCluskey

2010

Can J Anesth/J Can Anesth

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Purpose The purpose of this article is to review the effective options for the reversal of vitamin K antagonists (warfarin and it coumarin analogues) and to help identify the option best suited for the patient requiring urgent surgery. Principal findings Vitamin K antagonists, the mainstay in long-term anticoagulation therapy, can be reversed with the administration of vitamin K, frozen plasma (FP), recombinant factor VIIa (rFVIIa), or the recently approved four-factor prothrombin complex concentrate (PCC), OctaplexÒ. While there is little evidence to suggest a superiority of PCC over FP, the availability of PCC in Canada is an important therapeutic addition requiring a thorough understanding of its pharmacology and risk benefit profile for the reversal of vitamin K antagonists. The use of PCC in the management of microvascular bleeding should be limited to very specific indications and should not be indicated in the routine management of massive blood loss. Conclusions In order to limit the blood loss associated with surgery and the management of uncontrolled bleeding, PCC is an important addition to our therapeutic armamentarium in the reversal of vitamin K antagonists.

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Systematic Overview of Warfarin and Its Drug and Food Interactions

Cited by 1,004 publications

References 219 publications

Warfarin: an environment‐dependent switchable molecular probe

Warfarin: an environment‐dependent switchable molecular probe

Personalized Medicine: Understanding Probabilities and Managing Expectations

Reversal of vitamin K antagonists prior to urgent surgery

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