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Contribution of rivaroxaban to the international normalized ratio when switching to warfarin for anticoagulation as determined by simulation studies
Aim This study evaluated the influence of rivaroxaban 20 mg once daily on international normalized ratio (INR) during the co‐administration period when switching from rivaroxaban to warfarin. Methods We developed a calibrated coagulation model that was qualified with phase I clinical data. Prothromb...
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Published in: | British journal of clinical pharmacology 2015-06, Vol.79 (6), p.959-966 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Aim
This study evaluated the influence of rivaroxaban 20 mg once daily on international normalized ratio (INR) during the co‐administration period when switching from rivaroxaban to warfarin.
Methods
We developed a calibrated coagulation model that was qualified with phase I clinical data. Prothrombin time and INR values were simulated by use of phospholipid concentrations that matched Neoplastin Plus® and Innovin® reagents. To simulate the combined effects of rivaroxaban and warfarin on INR during switching, warfarin initiation was simulated by adjusting the magnitude of the warfarin effect to reach the desired target INRs over the course of 21 days. The warfarin effect values (obtained every 6 h) and the desired rivaroxaban plasma concentrations were used. Nomograms were generated from rivaroxaban induced increases in INR.
Results
The simulation had good prediction quality. Rivaroxaban induced increases in the total INR from the warfarin attributed INR were seen, which increased with rivaroxaban plasma concentration. When the warfarin only INR was 2.0–3.0, the INR contribution of rivaroxaban with Neoplastin Plus® was 0.5–1.2, decreasing to 0.3–0.6 with Innovin® at median trough rivaroxaban plasma concentrations (38 μg l−1).
Conclusions
The data indicate that measuring warfarin induced changes in INR are best performed at trough rivaroxaban concentrations (24 h after rivaroxaban dosing) during the co‐administration period when switching from rivaroxaban to warfarin. Furthermore, Innovin® is preferable to Neoplastin Plus® because of its substantially lower sensitivity to rivaroxaban, thereby reducing the influence of rivaroxaban on the measured INR. |
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ISSN: | 0306-5251 1365-2125 |
DOI: | 10.1111/bcp.12571 |