Pharmacodynamic profile and drug interactions with non-vitamin K antagonist oral anticoagulants: implications for patients with atrial fibrillation

INTRODUCTION: Non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to prevent ischemic stroke and systemic thromboembolism in patients with nonvalvular atrial fibrillation. Owing to their predictable pharmacological profiles, they can be given in fixed doses without the need for routine coagulation monitoring. However, their distinctive pharmacological properties also raise issues about potential drug interactions. AREAS COVERED: A literature search was conducted to extract published studies on the pharmacodynamics and drug interactions involving NOACs. Available data from US FDA and European Medicine Agency were also included. As these agents are substrates of permeability glycoprotein (P-gp) efflux transporter and/or CYP3A4 enzymes, articles focusing on the co-administration of NOACs and drugs affecting these pathways are discussed. Concomitant use of NOACs with antiplatelet agents may potentially increase bleeding risk. EXPERT OPINION: Measurement of anticoagulant effects is desired to evaluate the risk of thromboembolism or bleeding for patients with NOACs. Prescribers should be vigilant against combination prescription of NOACs with strong inhibitors (such as ketoconazole) or inducers of P-gp and/or CYP3A4 (such as rifampicin). Potential benefit of concurrent use of these agents with antiplatelet drugs should be cautiously balanced against latent risk in specific clinical situations.