Best Evidence Analyses and Commentary
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 have not.  

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.  

Conclusions/Recommendations:

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.  

  1. 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 2012;129:492-8.
  2. 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.
  3. 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.
  4. XARELTO® (rivaroxaban) Tablets Full Prescribing Information. Janssen Pharmaceuticals, Inc; Titusville, NJ: Revised November 2012.

 


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