Introduction Over the past 60 years, clinicians have used vitamin K antagonists, 
primarily warfarin, as the sole oral anticoagulants for managing a variety of 
thrombotic disorders. Warfarin, which requires frequent monitoring, has a 
variable dose response, a narrow therapeutic index, and numerous drug and 
dietary interactions. However, intravenous and subcutaneous agents, such as 
unfractionated heparin, low-molecular-weight heparin, direct thrombin 
inhibitors, and pentasaccharide, have been introduced over the past 30 years for 
managing thromboembolic disorders. Recently, 5 new oral anticoagulants, 
dabigatran, rivaroxaban, apixaban, endoxaban, and betrixaban, have been 
introduced into clinical trials. Apixaban, rivaroxaban, endoxaban, and 
betrixaban are specific direct inhibitors of factor Xa, while dabigatran 
inhibits factor IIa. These drugs have a pharmacological profile that does not 
require monitoring in order to adjust therapy, which is the mainstay of warfarin 
management. In addition, these new medications have not shown any major issues 
regarding food interactions; rather, they demonstrate the potential for limited 
drug-drug interactions due to their limited metabolism through the cytochrome 
P450 system. This unique pharmacokinetic profile may provide clinicians with a 
new era of managing thromboembolic disorders. Two of these agents, dabigatran 
and rivaroxaban, have been approved by the US Food and Drug Administration (FDA) 
for stroke prevention in patients with nonvalvular atrial fibrillation (AF); in 
addition, rivaroxaban can be used in the prevention of venous thromboembolism 
(VTE) in total hip and knee arthroplasty during the acute and extended periods 
of risk. However, the challenge for hospital formularies will be the appropriate 
use and management of these new medications as they become integrated into 
outpatient care. In order to better understand the issues that pharmacy and 
therapeutics committees will encounter, a review of the 2 FDA-approved oral 
anticoagulants will be evaluated.