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Author: Admin | 2025-04-28
Inhibitory potential for P-gp and ABCG2 transporters.The effects of coadministered drugs on the pharmacokinetics of rivaroxaban exposure are summarized in Figure 3 [see DRUG INTERACTIONS].Figure 3: Effect of Coadministered Drugs on the Pharmacokinetics of Rivaroxaban in AdultsAnticoagulantsIn a drug interaction study, single doses of enoxaparin (40 mg subcutaneous) and XARELTO (10 mg) given concomitantly resulted in an additive effect on anti-factor Xa activity. In another study, single doses of warfarin (15 mg) and XARELTO (5 mg) resulted in an additive effect on factor Xa inhibition and PT. Neither enoxaparin nor warfarin affected the pharmacokinetics of rivaroxaban (see Figure 3).NSAIDs/AspirinIn ROCKET AF, concomitant aspirin use (almost exclusively at a dose of 100 mg or less) during the double-blind phase was identified as an independent risk factor for major bleeding. NSAIDs are known to increase bleeding, and bleeding risk may be increased when NSAIDs are used concomitantly with XARELTO. Neither naproxen nor aspirin affected the pharmacokinetics of rivaroxaban (see Figure 3).ClopidogrelIn two drug interaction studies where clopidogrel (300 mg loading dose followed by 75 mg daily maintenance dose) and XARELTO (15 mg single dose) were coadministered in healthy subjects, an increase in bleeding time to 45 minutes was observed in approximately 45% and 30% of subjects in these studies, respectively. The change in bleeding time was approximately twice the maximum increase seen with either drug alone. There was no change in the pharmacokinetics of either drug.Drug-Disease Interactions With Drugs That Inhibit Cytochrome P450 3A Enzymes And Drug Transport SystemsIn a pharmacokinetic trial, XARELTO was administered as a single dose in subjects with mild (CrCl = 50 to 79 mL/min) or moderate renal impairment (CrCl = 30 to 49 mL/min) receiving multiple doses of erythromycin (a combined P-gp and moderate CYP3A inhibitor). Compared to XARELTO administered alone in subjects with normal renal function (CrCl >80 mL/min), subjects with mild and moderate renal impairment concomitantly receiving erythromycin reported a 76% and 99% increase in AUCinf and a 56% and 64% increase in Cmax, respectively. Similar trends in pharmacodynamic effects were also observed.QT/QTc ProlongationIn a thorough QT study in healthy men and women aged 50 years and older, no QTc prolonging effects were observed for XARELTO (15 mg and 45 mg, single-dose).Clinical StudiesStroke Prevention In Nonvalvular Atrial FibrillationThe evidence for the efficacy and safety of XARELTO was derived from Rivaroxaban Oncedaily oral direct factor Xa inhibition Compared with vitamin K antagonist for the prevention of
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