Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct Factor Xa inhibitor

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

AIM

This study evaluated the effects of impaired renal function on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban (10 mg single dose), an oral, direct Factor Xa inhibitor.

METHODS

Subjects (n= 32) were stratified based on measured creatinine clearance: healthy controls (≥80 ml min⁻¹), mild (50–79 ml min⁻¹), moderate (30–49 ml min⁻¹) and severe impairment (<30 ml min⁻¹).

RESULTS

Renal clearance of rivaroxaban decreased with increasing renal impairment. Thus, plasma concentrations increased and area under the plasma concentration–time curve (AUC) LS‐mean values were 1.44‐fold (90% confidence interval [CI] 1.1, 1.9; mild), 1.52‐fold (90% CI 1.2, 2.0; moderate) and 1.64‐fold (90% CI 1.2, 2.2; severe impairment) higher than in healthy controls. Corresponding values for the LS‐mean of the AUC for prolongation of prothrombin time were 1.33‐fold (90% CI 0.92, 1.92; mild), 2.16‐fold (90% CI 1.51, 3.10 moderate) and 2.44‐fold (90% CI 1.70, 3.49 severe) higher than in healthy subjects, respectively. Likewise, the LS‐mean of the AUC for Factor Xa inhibition in subjects with mild renal impairment was 1.50‐fold (90% CI 1.07, 2.10) higher than in healthy subjects. In subjects with moderate and severe renal impairment, the increase was 1.86‐fold (90% CI 1.34, 2.59) and 2.0‐fold (90% CI 1.44, 2.78) higher than in healthy subjects, respectively.

CONCLUSIONS

Rivaroxaban clearance is decreased with increasing renal impairment, leading to increased plasma exposure and pharmacodynamic effects, as expected for a partially renally excreted drug. However, the influence of renal function on rivaroxaban clearance was moderate, even in subjects with severe renal impairment.

DOI: 10.1111/j.1365-2125.2010.03753.x

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