Rivaroxaban

1 INDICATIONS AND USAGE XARELTO is a factor Xa inhibitor indicated: • to reduce risk of stroke and systemic embolism in nonvalvular atrial fibrillation ( 1.1 ) • for treatment of deep vein thrombosis (DVT) ( 1.2 ) • for treatment of pulmonary embolism (PE) ( 1.3 ) • for reduction in the risk of recurrence of DVT or PE ( 1.4 ) • for the prophylaxis of DVT, which may lead to PE in patients undergoing knee or hip replacement surgery ( 1.5 ) • for prophylaxis of venous thromboembolism (VTE) in acutely ill medical patients ( 1.6 ) • to reduce the risk of major cardiovascular events in patients with coronary artery disease (CAD) ( 1.7 ) • to reduce the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD), including patients after recent lower extremity revasc...

6 ADVERSE REACTIONS The following clinically significant adverse reactions are also discussed in other sections of the labeling: • Increased Risk of Stroke After Discontinuation in Nonvalvular Atrial Fibrillation [see Boxed Warning and Warnings and Precautions (5.1) ] • Bleeding Risk [see Warnings and Precautions (5.2 , 5.4 , 5.5 , 5.6 , 5.7) ] • Spinal/Epidural Hematoma [see Boxed Warning and Warnings and Precautions (5.3) ] • The most common adverse reaction (>5%) in adult patients was bleeding. ( 6.1 ) • The most common adverse reactions (>10%) in pediatric patients were bleeding, cough, vomiting, and gastroenteritis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

8.1 Pregnancy Risk Summary The limited available data on XARELTO in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. Use XARELTO with caution in pregnant patients because of the potential for pregnancy related hemorrhage and/or emergent delivery. The anticoagulant effect of XARELTO cannot be reliably monitored with standard laboratory testing. Consider the benefits and risks of XARELTO for the mother and possible risks to the fetus when prescribing XARELTO to a pregnant woman [see Warnings and Precautions (5.2 , 5.7) ] .

WARNING: (A) PREMATURE DISCONTINUATION OF XARELTO INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA WARNING: (A) PREMATURE DISCONTINUATION OF XARELTO INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA See full prescribing information for complete boxed warning. (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. 5 WARNINGS AND PRECAUTIONS • Risk of bleeding: XARELTO can cause serious and fatal bleeding. An agent to reverse the activity of rivaroxaban is available. ( 5.2 ) • Pregnancy-related hemorrhage: Use XARELTO with caution in pregnant women due to the potential for obstetric hemorrhage and/or emergent delivery. ( 5.7 , 8.1 ) • Prosthetic heart valves: XARELTO use not recommended. ( 5.8 ) • Increased Risk of Thrombosis in Patients with Triple Positive Antiphospholipid Syndrome: XARELTO use not recommended. ( 5.10 ) 5.1 Increased Risk of Thrombotic Events after Premature Discontinuation Premature discontinuation of any oral anticoagulant, including XARELTO, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. 4 CONTRAINDICATIONS XARELTO is contraindicated in patients with: • active pathological bleeding [see Warnings and Precautions (5.2) ] • severe hypersensitivity reaction to XARELTO (e.g., anaphylactic reactions) [see Adverse Reactions (6.2) ] • Active pathological bleeding ( 4 ) • Severe hypersensitivity reaction to XARELTO ( 4 )