Switching from Rivaroxaban to Warfarin: Pharmacodynamics, Safety Assessed in Study
the MPR take:
Because of various clinical situations, there may be a need for clinicians to transition patients from one anticoagulant therapy to another. In order to do this safely, the pharmacology profiles of both agents should be taken into consideration. A new study in the British Journal of Clinical Pharmacology sought to assess pharmacodynamic changes during transition from rivaroxaban, a selective direct Factor Xa inhibitor, to warfarin in healthy subjects, with safety, tolerability, and pharmacokinetics as secondary objectives. In the open-label, non-randomized, sequential two-period study of healthy subjects ages 18–60 years of age, the patients underwent a 28-day screening phase, an approximately 14 day initial treatment period, and a second treatment period of about 8 days. A 14 day wash-out period was included between the two treatment periods. In the first treatment period, patients received rivaroxaban monotherapy 20mg/daily for five days, followed by co-administration of rivaroxaban 20mg/day and warfarin (5mg or 10mg) for 2–4 days. Rivaroxaban was stopped when trough INR values ≥2.0 were achieved and patients continued on their warfarin treatment as monotherapy (INR 2.0–3.0). In the second treatment period, patients received warfarin monotherapy but without rivaroxaban. During the co-administration in the first treatment period, maximum INR and prothrombin time values were greater than with rivaroxaban or warfarin monotherapy. Rivaroxaban had the smallest effect on INR at trough rivaroxaban levels and neither drug significantly impacted maximum plasma concentrations of the other drug. The authors recommend that when transitioning from rivaroxaban to warfarin, INR monitoring during co-administration should be performed at the trough rivaroxaban level to minimize the rivaroxban effect on INR.
The primary objective was to explore the pharmacodynamic changes during transition from rivaroxaban to warfarin in healthy subjects. Safety, tolerability and pharmacokinetics were assessed as secondary objectives.