Direct oral anticoagulants--pharmacology, drug interactions, and side effects.

The direct thrombin inhibitor, dabigatran, as well as the direct factor Xa inhibtors rivaroxaban, apixaban, and edoxaban, display pharmacodynamic features quite similar to low-molecular-weight heparins, with a time to peak level of 1-4 hours after oral administration, and a half-life between 5 and 14 hours. All drugs display a linear relationship and a high degree of correlation between drug levels in plasma, and the anticoagulant effect. Major differences are the extent of renal elimination (with 80% or more for dabigatran, 66% for rivaroxaban [33% unchanged, active drug, and 33% inactive metabolites], 33% for edoxaban, and finally, 25% for apixaban), and bioavailability, which determines the amount of drug required for attaining the target plasma concentration of the drug. Due to the reliable pharmacokinetics and pharmacodynamics, no routine laboratory monitoring is necessary, although dedicated laboratory assays are available for emergencies and some other specific conditions.