INTRODUCTION

Warfarin and other vitamin K antagonists (VKAs; eg, acenocoumarol, phenprocoumon, fluindione) are the standard oral anticoagulants used in a variety of clinical settings. The general principles underlying the clinical use of VKAs, including their complications and laboratory monitoring, will be reviewed here [1]. Other aspects of VKA therapy are discussed separately:

• The outpatient management of the patient taking warfarin, including the importance of strict INR control (see "Outpatient management of oral anticoagulation", section on 'Importance of strict INR control')
• Correction of excess anticoagulation on warfarin therapy (see "Correcting excess anticoagulation after warfarin")
• Management of anticoagulation in patients who have had, or are at risk for, intracranial bleeding (see 'Intracranial bleeding' below)
• A patient information document on warfarin therapy (see "Patient information: Warfarin (Coumadin) (Beyond the Basics)")

BIOLOGICAL PROPERTIES

Warfarin — Commercially-available warfarin is a racemic mixture of S and R enantiomers. The more potent S form of the drug is metabolized primarily by the CYP2C9 hepatic microsomal enzyme system. This enzyme system is inducible by many drugs and has a number of genetic variants, both of which may profoundly alter warfarin's in vivo activity (see 'Genetic interactions' below).

Warfarin is strongly protein-bound, primarily to albumin; only the non-protein-bound fraction is biologically active. Accordingly, any agent that is also bound to albumin may displace warfarin from its albumin binding sites and increase its biological activity.

Warfarin is water soluble and completely absorbed after oral administration. The majority of the drug is absorbed in the proximal small bowel, although successful use of the sublingual route has been described in two patients [2,3]. Excretion is via the urine, primarily as drug metabolites.