Response prepared by: Katie Kelly, PharmD; Abbey Powers, PharmD
Currently, there is limited evidence on proper monitoring techniques for rivaroxaban in
regards to INR. We have contacted the manufacturer (Janssen) and have received information regarding
ex vivo/in vitro studies conducted. Some of these studies have been published, while others
Asmis et al. (2012)1 – conducted a study to evaluate
the feasibility of rivaroxaban quantification with a commercial anti-Fx assay and to assess its
accuracy and precision across 9 laboratories. In addition, the influence of rivaroxaban 10 mg on
routine coagulation tests in the different laboratories was assessed using plasma samples from 20
healthy volunteers taken 2-3 hours following rivaroxaban ingestion. Thrombin time, Fibrinogen,
FXIII, and D-Dimer results were not affected by rivaroxaban, and PT, INR, and aPTT were
significantly altered by rivaroxaban (p≤0.05).
Samama et al. (2010)2 – conducted an in vitro
study to evaluate the effects of rivaroxaban on various coagulation assays to determine whether a
commercially available assay could accurately and appropriately assess rivaroxaban
pharmacodynamics. The results of this study showed that several coagulation tests, including PT,
with rivaroxaban specific calibration, prothrombinase-induced clotting time (PiCT), and heparin
clotting time, may be appropriate to assess the pharmacodynamics of rivaroxaban. PT is currently
reported as a percentage of normal or as an INR value; neither is appropriate for rivaroxaban
assessment. Currently, INR is calibrated and validated for vitamin K antagonists only. There is
currently one in vitro feasibility study that supports the use of INR calibration with an
international sensitivity index (ISI) derived specifically for rivaroxaban.3
Tripodi et al.(2011)3 – conducted an in vitro
study to assess the feasibility of using the INR calibrated for rivaroxaban to normalize PT results
for rivaroxaban treated patients. The study listed above described that PT was prolonged in a
concentration dependent manner; however there is inter-variability among specific reagents used.
This study aimed to develop an ISI through testing for PT with thromboplastins. This ISI was then
utilized to obtain an INR calibrated for rivaoxaban. Results of this in vitro study support
possible INR calibration for rivaroxaban, but also states that further in vivo testing needs
to be done.
There is limited data supporting the direct association between rivaroxaban
and INR. However, FDA approved labeling for rivaroxaban states that it affects INR, and it is
recommended that this be taken into consideration when switching patients between warfarin to
rivaroxaban. Also, the manufacturer recommends that INR not be used to monitor rivaroxaban.
- Asmis LM, Alberio L,
Angelillo-Scherrer A, et al. Rivaroxaban: quantification by anti-Fxa assay and influence on
coagulation tests. A study in 9 Swiss laboratories. Thrombosis Research
- Samama MM, Martinoli J, LeFlem L, et
al. Assessment of laboratory assays to measure rivaroxaban – an oral, direct factor Xa
inhibitor. Thromb Haemost 2010;103(4):815-25.
- Tripodi A, Chantarangkul V, Guinet
C, Samama MM. The international normalized ratio calibrated for rivaroxaban has the potential
to normalize prothrombin time results for rivaroxaban-treated patients: results of an in-vitro
study. Thromb Haemost 2011;9(1):226-228.
- XARELTO® (rivaroxaban) Tablets
Full Prescribing Information. Janssen Pharmaceuticals, Inc; Titusville, NJ: Revised November