Pharmacokinetics and Pharmacodynamics of the Nonvitamin K Antagonist Oral Anticoagulant Edoxaban When Administered Alone or After Switching from Rivaroxaban or Dabigatran Etexilate in Healthy Subjects.
Clin Drug Investig
; 36(2): 127-36, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26597179
ABSTRACT
BACKGROUND AND OBJECTIVES:
Edoxaban is an oral, once-daily direct factor Xa inhibitor. To support the possibility that patients may choose to switch treatment from another nonvitamin K antagonist oral anticoagulant to edoxaban, this clinical study was conducted to evaluate the pharmacokinetic and pharmacodynamic effects of edoxaban after switching from rivaroxaban or dabigatran etexilate to edoxaban.METHODS:
In this open-label, three-period, crossover study, healthy subjects received 3 days of edoxaban 60 mg daily, rivaroxaban 20 mg daily, or dabigatran etexilate 150 mg twice daily, followed by edoxaban 60 mg on day 4.RESULTS:
Day 4 edoxaban pharmacokinetic parameters were similar for all treatments. The peak effect of edoxaban on prothrombin time (PT) after 4 days of edoxaban only was 21.8 ± 2.46 s; after switching from rivaroxaban to edoxaban, peak effect on PT was similar at 21.8 ± 2.88 s. After switching from dabigatran etexilate to edoxaban, least squares mean activated partial thromboplastin time (aPTT) at 2 h after administration was 47.6 vs 35.0 s for edoxaban alone. The treatment difference was 12.8 s (95% confidence interval 10.5-15.1; p < 0.0001). Post hoc analysis revealed that predose aPTT was elevated on day 3 of dabigatran etexilate administration, and on day 4, indicating a carryover effect from dabigatran. All treatments were well tolerated and there were no safety concerns upon switching, with no increased risk of bleeding.CONCLUSIONS:
The study results suggest that switching to edoxaban from either rivaroxaban or dabigatran etexilate at the time of the next dose is well tolerated and maintains coagulation status.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Piridinas
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Tiazóis
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Rivaroxabana
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Dabigatrana
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Anticoagulantes
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article