Pharmacokinetics and pharmacodynamics

The relationship between DOAC levels and standard measures of anticoagulation, such as the INR and activated partial thromboplastin time and drug levels is non-linear. Therefore, these measures do not help determine anticoagulation efficacy and routine monitoring is not required.34 

The pharmacokinetics of DOACs differ markedly from those of warfarin. DOACs have more consistent and predictable dose-response and time to reach steady state than warfarin, for example. The actions of DOACs depend on the plasma concentration rather than the synthesis of clotting factors. Therefore, the onset of action with DOACs is more rapid than with warfarin, achieving full anticoagulation within 1–2 hours of dosing.34,40

The half-lives of apixaban (9–14 hours), dabigatran (12–17 hours), edoxaban (10–14 hours) and rivaroxaban (7–11 hours) are shorter than that of warfarin.40,45 Also, the offset of action is more rapid than with warfarin: most of the anticoagulation effect has disappeared within 24 hours of the last dose.34 Moreover, DOACs show minimal interactions with diet. However, clinicians should recommend that patients take rivaroxaban and dabigatran with food to ensure optimal uptake and reduce the risk of dyspepsia respectively.34

Review the efficacy of direct oral anticoagulants in the next section

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