XARELTO ® (rivaroxaban)

XARELTO (rivaroxaban) tablets, for oral use
Initial U.S. Approval: 2011

(2) for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing knee or hip replacement surgery

USE IN SPECIFIC POPULATIONS
Nursing mothers: discontinue drug or discontinue nursing

Renal impairment:
Prophylaxis of DVT: Avoid use in patients with severe impairment (CrCl <30 mL/min).
Use with caution in moderate impairment (CrCl 30 to <50 mL/min)

Pregnancy related hemorrhage: Use XARELTO with caution in pregnant women due to the potential for obstetric hemorrhage and/or emergent delivery. Promptly evaluate signs and symptoms of blood loss.

DRUG INTERACTIONS
Combined P-gp and strong CYP3A4 inhibitors and inducers: Avoid concomitant use.
Prophylaxis of DVT: Anticoagulants: Avoid concomitant use

The most common adverse reaction (>5%) was bleeding.

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.

2.1 Nonvalvular Atrial Fibrillation

For patients with creatinine clearance (CrCl) >50 mL/min, the recommended dose of XARELTO is 20 mg taken orally once daily with the evening meal. For patients with CrCl 15 to 50 mL/min, the recommended dose is 15 mg once daily with the evening meal [see package insert for Use in Specific Populations (8.7)].

Switching from or to Warfarin - When switching patients from warfarin to XARELTO, discontinue warfarin and start XARELTO as soon as the International Normalized Ratio (INR) is below 3.0 to avoid periods of inadequate anticoagulation.

No clinical trial data are available to guide converting patients from XARELTO to warfarin. XARELTO affects INR, so INR measurements made during co-administration with warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue XARELTO and begin both a parenteral anticoagulant and warfarin at the time the next dose of XARELTO would have been taken.

Switching from or to Anticoagulants other than Warfarin - For patients currently receiving an anticoagulant other than warfarin, start XARELTO 0 to 2 hours prior to the next scheduled evening administration of the drug (e.g., low molecular weight heparin or non-warfarin oral anticoagulant) and omit administration of the other anticoagulant. For unfractionated heparin being administered by continuous infusion, stop the infusion and start XARELTO at the same time.

For patients currently taking XARELTO and transitioning to an anticoagulant with rapid onset, discontinue XARELTO and give the first dose of the other anticoagulant (oral or parenteral) at the time that the next XARELTO dose would have been taken.

2.2 Prophylaxis of Deep Vein Thrombosis
The recommended dose of XARELTO is 10 mg taken orally once daily with or without food. The initial dose should be taken at least 6 to 10 hours after surgery once hemostasis has been established.

-For patients undergoing hip replacement surgery, treatment duration of 35 days is recommended.
-For patients undergoing knee replacement surgery, treatment duration of 12 days is recommended.

2.3 General Dosing Instructions
Hepatic Impairment:
No clinical data are available for patients with severe hepatic impairment. Avoid use of XARELTO in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment or with any hepatic disease associated with coagulopathy [see Use in Specific Populations (8.8)].

Renal Impairment:
Nonvalvular Atrial Fibrillation:
Avoid the use of XARELTO in patients with CrCl <15 mL/min. Periodically assess renal function as clinically indicated (i.e., more frequently in situations in which renal function may decline) and adjust therapy accordingly. Discontinue XARELTO in patients who develop acute renal failure while on XARELTO [see Use in Specific Populations (8.7)].

Prophylaxis of Deep Vein Thrombosis:
Avoid the use of XARELTO in patients with severe renal impairment (CrCl <30 mL/min) due to an expected increase in rivaroxaban exposure and pharmacodynamic effects in this patient population. Observe closely and promptly evaluate any signs or symptoms of blood loss in patients with moderate renal impairment (CrCl 30 to 50 mL/min). Patients who develop acute renal failure while on XARELTO should discontinue the treatment [see Use in Specific Populations (8.7)].

Surgery and Intervention:
If anticoagulation must be discontinued to reduce the risk of bleeding with surgical or other procedures, XARELTO should be stopped at least 24 hours before the procedure. In deciding whether a procedure should be delayed until 24 hours after the last dose of XARELTO, the increased risk of bleeding should be weighed against the urgency of intervention. XARELTO should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established. If oral medication cannot be taken after surgical intervention, consider administering a parenteral anticoagulant.

Missed Dose:
If a dose of XARELTO is not taken at the scheduled time, administer the dose as soon as possible on the same day.

Use with P-gp and Strong CYP3A4 Inhibitors or Inducers:
Avoid concomitant use of XARELTO with combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, and conivaptan) [see Drug Interactions (7.1)].

Avoid concomitant use of XARELTO with drugs that are combined P-gp and strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort)

XARELTO (rivaroxaban) Tablets are available in the strengths and packages listed below:

10 mg tablets are round, light red, biconvex film-coated tablets marked with a triangle pointing down above a "10" on one side, and an "Xa" on the other side. The tablets are supplied in the packages listed:
NDC 50458-580-30 Bottle containing 30 tablets
NDC 50458-580-10 Blister package containing 100 tablets (10 blister cards containing 10 tablets each)

15 mg tablets are round, red, biconvex film-coated tablets with a triangle pointing down above a "15" marked on one side and "Xa" on the other side. The tablets are supplied in the packages listed:
NDC 50458-578-30 Bottle containing 30 tablets
NDC 50458-578-90 Bottle containing 90 tablets
NDC 50458-578-10 Blister package containing 100 tablets (10 blister cards containing 10 tablets each)

20 mg tablets are triangle-shaped, dark red film-coated tablets with a triangle pointing down above a "20" marked on one side and "Xa" on the other side. The tablets are supplied in the packages listed:
NDC 50458-579-30 Bottle containing 30 tablets
NDC 50458-579-90 Bottle containing 90 tablets
NDC 50458-579-10 Blister package containing 100 tablets (10 blister cards containing 10 tablets each)

Store at 25° C (77° F) or room temperature; excursions permitted to 15°–30° C (59°–86° F) [see USP Controlled Room Temperature].

Keep out of the reach of children.

Finished Product Manufactured by:
Janssen Ortho, LLC
Gurabo, PR 00778

Manufactured for:
Janssen Pharmaceuticals, Inc.
Titusville, NJ 08560

Licensed from:
Bayer HealthCare AG
51368 Leverkusen, Germany

© Janssen Pharmaceuticals, Inc. 2011

Trademarks are property of their respective owners.

PRINCIPAL DISPLAY PANEL - 10 mg Tablet Bottle Label

NDC 50458-580-30
30 Tablets

Xarelto®
(rivaroxaban)