Products

Vaxato

Indication
Oral Anticoagulant

Pharmaceutical Form
film-coated tablets

Rivaroxaban 10mg

Rivaroxaban is a highly selective direct factor Xa inhibitor with high oral bioavailability. Inhibition of Factor Xa interrupts the intrinsic and extrinsic pathway of the blood coagulation cascade, inhibiting both thrombin formation and development of thrombi. Rivaroxaban does not inhibit thrombin (activated Factor II) and no effects on platelets have been demonstrated.

Clinical efficacy and safety

The Rivaroxaban clinical programme was designed to demonstrate the efficacy of Rivaroxaban for the prevention of VTE (venous thromboembolism), i.e. proximal and distal deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing major orthopedic surgery of the lower limbs. Over 9,500 patients (7,050 in total hip replacement surgery and 2,531 in total knee replacement surgery) were studied in controlled randomized double-blind phase III clinical studies, the RECORD-programme. Rivaroxaban 10mg once daily (od) started no sooner than 6 hours post-operatively was compared with enoxaparin 40mg once daily started 12 hours pre-operatively.

In all three phase III studies, Rivaroxaban significantly reduced the rate of total VTE (any venographically detected or symptomatic DVT, non-fatal PE and death) and major VTE (proximal DVT, non-fatal PE and VTE-related death), the pre-specified primary and major secondary efficacy endpoints. Furthermore, in all three studies the rate of symptomatic VTE (symptomatic DVT, nonfatal PE, VTE-related death) was lower in Rivaroxaban treated patients compared to patients treated with enoxaparin. The main safety endpoint, major bleeding, showed comparable rates for patients treated with 10mg compared to enoxaparin 40mg.

Absorption

Rivaroxaban is rapidly absorbed with maximum concentration (cmax) appearing 2-4 hours after tablet intake.

Oral absorption of Rivaroxaban is almost complete and oral bioavailability is high (80-100%), irrespective of fasting/fed conditions, intake with food dose not affects Rivaroxaban AUC or Cmax. Rivaroxaban can be taken with or without food.

Rivaroxaban 10mg pharmacokinetics is approximately linear up to about 15mg once daily

Distribution

Plasma protein binding in humans is high at approximately 92-95%, with serum albumin being the main binding component. The volume of distribution is moderate with Vss being approximately 50 liters.

Elimination

Of the administered Rivaroxaban dose, approximately 2/3 undergoes metabolic degradation, with half then being eliminated renally and the other half eliminated by the fecal route. The final 1/3 of the administered dose undergoes direct renal excretion as unchanged active substance in the urine, mainly via active renal secretion

Therapeutic indications:

 Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery