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Handling delayed or missed direct oral anticoagulant doses: model-informed individual remedial dosing

Xiao-Qin Liu1, Zi-Ran Li2, Chen-Yu Wang1

  • 1Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Blood Advances
|September 18, 2024
PubMed

Insights

Individualized dosing strategies for direct oral anticoagulants (DOACs) can mitigate risks from missed or delayed doses. This approach, using pharmacokinetic modeling, offers better solutions than current guidelines for managing nonadherence to anticoagulation therapy.

Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Pharmacometrics

Background:

  • Nonadherence to direct oral anticoagulants (DOACs) increases risks of thromboembolism and bleeding.
  • Current guidelines for managing delayed or missed DOAC doses lack individualization and evidence.
  • Delayed or missed doses are the most frequent forms of nonadherence.

Purpose of the Study:

  • To develop individualized remedial dosing strategies for delayed or missed DOAC doses.
  • To create a tool for recommending personalized dosing adjustments based on patient factors and delay duration.
  • To improve patient safety by minimizing time outside the therapeutic range.

Main Methods:

  • Population pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation were used to develop dosing strategies.
  • Data from published literature on DOACs (rivaroxaban, apixaban, edoxaban, dabigatran etexilate) were analyzed.
  • A web-based dashboard (R-shiny) was created to provide real-time dosing recommendations.

Main Results:

  • Remedial dosing regimens were designed to rapidly restore therapeutic drug concentrations or biomarkers.
  • The developed strategies showed less deviation time outside the therapeutic range compared to current recommendations.
  • Patient-specific factors like age, weight, renal function, and polypharmacy had minor impacts on strategies.

Conclusions:

  • Individualized remedial dosing strategies for DOACs are superior to current guidelines.
  • The R-shiny dashboard provides a practical tool for clinicians to manage missed or delayed DOAC doses effectively.
  • Personalized strategies help mitigate the risks of bleeding and thrombosis associated with DOAC nonadherence.

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