Drug-drug interactions of non-vitamin K oral anticoagulants

ABSTRACT

Introduction: The approval of non-vitamin K oral anticoagulants (NOACs) as antithrombotic alternatives to vitamin K antagonists (VKAs) has changed clinical practice. However, the efficacy and safety of the four most commonly used NOACs (dabigatran, rivaroxaban, apixaban and edoxaban) might be compromised by co-administration of other medications used for various major comorbidities. Dose adjustment of the NOACs may be needed to avert cases of concomitant medication affecting NOACs absorption, metabolism and coagulation.

Areas covered: This review summarizes the current knowledge regarding drug-drug interactions of NOACs in order to guide health professionals regarding the dose modification required if the NOACs are co-administered with other medication with potential significant interactions. The data were acquired from searches of PubMed and also from the NOAC reports to the European Medicines Agency and Food and Drug Administration Agency.

Expert opinion: Most of the studies in this field have been organized by pharmaceutical companies. Independent research and registries will provide more information in the near future about the drug-drug interactions of NOACs. P-glycoprotein transporter and cytochrome P450 enzyme complexes appear to be the main pathways where the most drug-drug interactions with NOACs occur.

KEYWORDS:

• Non-vitamin K oral anticoagulants
• drug-drug interactions
• P-glycoprotein
• cytochrome P450(CYP)
• dabigatran
• rivaroxaban
• apixaban
• edoxaban

Article highlights

• NOACs have preferable pharmacokinetic and pharmacodynamic profile compared with VKAs, with less food and drug-drug interactions

• P-glycoprotein efflux transporter and cytochrome P450(CYP) are the main interaction mechanisms of NOACs with other drugs

• Physicians should consider pharmacokinetic effects of other simultaneously used drugs and of co-morbidities when prescribing NOACs

• Most data investigating drug–drug interactions of NOACs are from manufacture-led studies.

• The current knowledge that we have so far regarding NOACs drug-drug interactions is limited but more data are emerging.

This box summarizes key points contained in the article.

Declaration of interest

GYH Lip is a member of the Scientific Documents Committee, European Heart Rhythm Association (EHRA); reviewer for various guidelines and position statements from ESC, EHRA, NICE etc. Steering Committees/trials: Includes steering committees for various Phase II and III studies, Health Economics & Outcomes Research, etc.; investigator in various clinical trials in cardiovascular disease, including those on antithrombotic therapies in atrial fibrillation, acute coronary syndrome, lipids, etc.; consultant for Bayer/Jensen J&J, Astellas, Merck, Sanofi, BMS/Pfizer, Biotronik, Medtronic, Portola, Boehringer Ingelheim, Microlife and Daiichi-Sankyo; speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Microlife, Roche and Daiichi-Sankyo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.