Comparison of warfarin and new antithrombotic drugs in terms of drug interactions

The stability of anticoagulation is essential for the efficacy and safety of warfarin therapy and treatment with new antithrombotic drugs.

Drug interactions play a dominant role in the emergence of overanticoagulation or an insufficient effect of antithrombotic therapy. The

pathway from warfarin ingestion to its therapeutic effect is very complicated and its biodegradation is mediated by different cytochrome

enzymes, with warfarin thus being prone to numerous drug interactions. The most important of them are interactions with inhibitors

and inducers of cytochrome 2C9, but numerous other pharmacologic mechanisms are also involved. The new direct thrombin inhibitors

(dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban) have predictable pharmacokinetics and a simple mechanism of action.

The pharmacokinetics of these antithrombotic drugs leads to a low risk of drug interactions; they are limited to P-glycoprotein inhibitors

and inducers, which influence the level of dabigatran, drugs inhibiting both P-glycoprotein and CyP 3A4, which increase rivaroxaban

and apixaban exposure, and inducers of P-glycoprotein and/or CyP 3A4, which induce a reduction in rivaroxaban and apixaban levels.

Keywords: warfarin, a new antithrombotic agents, drug interactions