XARELTO- rivaroxaban tablet, film coated
XARELTO- rivaroxaban
Janssen Pharmaceuticals, Inc.
WARNING: (A) PREMATURE DISCONTINUATION OF XARELTO INCREASES THE RISK OF THROMBOTIC EVENTS,
A. Premature discontinuation of XARELTO increases the risk of thrombotic events
Premature discontinuation of any oral anticoagulant, including XARELTO, increases the risk of thrombotic events. If anticoagulation with XARELTO is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant.
B. Spinal/epidural hematoma
Epidural or spinal hematomas have occurred in patients treated with XARELTO who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:
use of indwelling epidural catheters
concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
a history of traumatic or repeated epidural or spinal punctures
a history of spinal deformity or spinal surgery
optimal timing between the administration of XARELTO and neuraxial procedures is not known
[see Warnings and Precautions (5.2, 5.3) and Adverse Reactions (6.2)].
Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary [see Warnings and Precautions (5.3)].
Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis [see Warnings and Precautions (5.3)].
1 INDICATIONS AND USAGE
1.1 Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation
XARELTO is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.
There are limited data on the relative effectiveness of XARELTO and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well-controlled [see Clinical Studies (14.1)].
1.2 Treatment of Deep Vein Thrombosis
XARELTO is indicated for the treatment of deep vein thrombosis (DVT).
1.3 Treatment of Pulmonary Embolism
XARELTO is indicated for the treatment of pulmonary embolism (PE).
1.4 Reduction in the Risk of Recurrence of Deep Vein Thrombosis and of Pulmonary Embolism
XARELTO is indicated for the reduction in the risk of recurrence of deep vein thrombosis and of pulmonary embolism following initial 6 months treatment for DVT and/or PE.
1.5 Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery
XARELTO is indicated for the prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery.
DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage
Indication
Dosage
Reduction in Risk of Stroke in Nonvalvular Atrial Fibrillation (2.4)
CrCl >50 mL/min:
20 mg once daily with the evening meal
CrCl 15 to 50 mL/min:
15 mg once daily with the evening meal
Treatment of DVT (2.5)Treatment of PE (2.5)
15 mg twice daily with food, for first 21 days
?after 21 days, transition to ?
20 mg once daily with food, for remaining treatment
Reduction in the Risk of Recurrence of DVT and of PE (2.5)
20 mg once daily with food
Prophylaxis of DVT Following Hip or Knee Replacement Surgery (2.6)
Hip replacement:
10 mg once daily for 35 days
Knee replacement:
10 mg once daily for 12 days
2.2 Important Food Effect Information
The 15 mg and 20 mg XARELTO tablets should be taken with food, while the 10 mg tablet can be taken with or without food
DESCRIPTION
Rivaroxaban, a FXa inhibitor, is the active ingredient in XARELTO Tablets with the chemical name 5-Chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide. The molecular formula of rivaroxaban is C19 H18 ClN3 O5 S and the molecular weight is 435.89
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
XARELTO is a selective inhibitor of FXa. It does not require a cofactor (such as Anti-thrombin III) for activity. Rivaroxaban inhibits free FXa and prothrombinase activity. Rivaroxaban has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. By inhibiting FXa, rivaroxaban decreases thrombin generation.
