How to handle the delayed or missed dose of rivaroxaban in patients with non-valvular atrial fibrillation: model-informed remedial dosing. Issue 9 (2nd September 2021)

• Record Type: Journal Article
• Authors: Liu, Xiao-Qin; Yin, Yi-Wei; Wang, Chen-Yu; Li, Zi-Ran; Zhu, Xiao; Jiao, Zheng
• Is Part Of: Expert review of clinical pharmacology. Volume 14:Issue 9(2021)
• Page Start: 1153
• Page End: 1163
• Publication Date: 2021-09-02
• Subjects: Rivaroxaban -- population pharmacokinetics -- pharmacodynamics -- modeling and simulation -- adherence; Clinical pharmacology -- Periodicals; 615.105
• DOI: 10.1080/17512433.2021.1937126
• Languages: English
• ISSNs: 1751-2433

Abstract

ABSTRACT: Background: Rivaroxaban is an oral anticoagulant widely used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. This study aimed to explore appropriate remedial dosing regimens for non-adherent rivaroxaban-treated patients. Methods: Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic (PK/PD) model for patients with NVAF was employed to design remedial dosing regimens. The proposed regimens were compared with remedial strategies in the European Heart Rhythm Association (EHRA) guide by assessing deviation time in terms of drug concentration, factor Xa activity, and prothrombin time. Results: The proposed remedial dosing regimens were dependent on delay duration. The missed dose should be taken immediately when the delay does not exceed 6 h; a half dose is advisable when the delay is between 6 and 20 h. A missed dose should be skipped if less than 4 h remains before the next dose. The proposed regimens resulted in shorter deviation time than that of the EHRA guide. Conclusion: PK/PD modeling and simulation provide valid evidence on the remedial dosing regimen of rivaroxaban, which could help to minimize the risk of bleeding and thromboembolism.