ri-va-ROX-a-ban

• Prevention of deep vein thrombosis (DVT) that may lead to pulmonary embolism (PE) following knee or hip replacement surgery.
• Prevention of venous thromboembolism (VTE) and VTE-related death during hospitalization and following hospital discharge in patients admitted for an acute medical illness who are at risk for thromboembolic complications and not at high risk of bleeding.
• Treatment of DVT or PE.
• Reduction in risk of recurrence of DVT and/or PE in patients at continued risk for recurrent DVT or PE after completion of initial treatment for at least 6 mo.
• Reduction in risk of stroke/systemic embolism in patients with nonvalvular atrial fibrillation (AF).
• Reduction in risk of major cardiovascular events (cardiovascular death, MI, and stroke) in patients with chronic coronary artery disease (in combination with aspirin).
• Reduction in risk of major thrombotic vascular events (MI, ischemic stroke, acute limb ischemia, and major amputation of a vascular etiology) in patients with peripheral artery disease (PAD), including patients who have recently undergone a lower extremity revascularization procedure due to symptomatic PAD (in combination with aspirin).

• Acts as selective factor X inhibitor that blocks the active site of factor Xa, inactivating the cascade of coagulation.

• Treatment and prevention of thromboembolic events and major cardiovascular events.

Absorption: Well absorbed (80%) following oral administration; absorption occurs in the stomach and ↓ as it enters the small intestine.

Distribution: Unknown.

Metabolism/Excretion: 51% metabolized by the liver; 36% excreted unchanged in urine. Metabolites do not have anticoagulant activity.

Half-life: 5–9 hr.

Contraindicated in:

• Hypersensitivity
• Active major bleeding
• Severe renal impairment (CCr <15 mL/min [DVT/PE treatment or prevention])
• Prosthetic heart valves
• Transcatheter aortic valve replacement (↑ risk of death and bleeding)
• Moderate to severe hepatic impairment (Child-Pugh B or C) or any liver pathology resulting in altered coagulation
• PE with hemodynamic instability or requiring thrombolysis or pulmonary embolectomy
• Concurrent use of drugs that are combined P-gp inducers/strong CYP3A4 inducers or combined P-gp inhibitors/strong CYP3A4 inhibitors
• Triple positive antiphospholipid syndrome (↑ risk of thrombosis)
• Lactation: Lactation.

Use Cautiously in:

• Neuroaxial spinal anesthesia or spinal puncture, especially if concurrent with an indwelling epidural catheter, drugs affecting hemostasis, history of traumatic/repeated spinal puncture or spinal deformity (↑ risk of spinal hematoma)
• CCr 50 mL/min (AF) (↓ dose)
• Use of feeding tube (proper placement of tube must be documented to ensure absorption)
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Rep: Women of reproductive potential with abnormal uterine bleeding (↑ risk of uterine bleeding)
• Pedi: Safety and effectiveness not established in children.

Derm: blister, pruritus.

Hemat: BLEEDING.

Local: wound secretion.

MS: extremity pain, muscle spasm.

Neuro: syncope.

Drug-Drug:

• Rivaroxaban acts as a substrate of these subsets of the CYP450 enzyme system: CYP3A4/5, CYP2J2, and ATP-binding cassette G2 (ABCG2). Drugs that inhibit or induce these systems may alter effectiveness.
• Concurrent use of drugs that are combined P-gp inhibitors/strong CYP3A4 inhibitors, including ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir, and conivaptan may ↑ levels; avoid concomitant use
• Concurrent use of drugs that are combined P-gp inducers/strong CYP3A4 inducers, including carbamazepine, phenytoin, or rifampin may ↓ levels; avoid concomitant use.
• Concurrent use of drugs that are combined P-gp inhibitors/moderate CYP3A4 inhibitors, including erythromycin in patients with renal impairment (CCr 15–79 mL/min) may ↑ levels; avoid concomitant use.
• ↑risk of bleeding with other anticoagulants, aspirin, clopidogrel, ticagrelor, prasugrel, fibrinolytics, NSAIDs, SNRIs, or SSRIs.

Drug-Natural Products:

• St. John's wort may ↓ levels; avoid concomitant use.

Prevention of DVT Following Knee or Hip Replacement Surgery

• PO (Adults): 10 mg once daily, initiated 6–10 hr postoperatively (when hemostasis is achieved) continued for 35 days after hip replacement or 12 days after knee replacement.

Prevention of VTE in Acutely Ill Medical Patients at Risk for Thromboembolic Complications Not at High Risk of Bleeding

• PO (Adults): 10 mg once daily while in the hospital and after hospital discharge for a total of 31–39 days.

Treatment of DVT or PE

• PO (Adults): 15 mg twice daily for 21 days, then 20 mg once daily for remainder of treatment period.

Reduction in Risk of Recurrent DVT and/or PE in Patients at Continued Risk for Recurrent DVT and/or PE

• PO (Adults): 10 mg once daily to be initiated after 6 mo of standard anticoagulant treatment.

Reduction in Risk of Stroke/Systemic Embolism in Nonvalvular AF

• PO (Adults): 20 mg once daily with evening meal.

Reduction in Risk of Major Cardiovascular Events in Patients with Chronic Coronary Artery Disease or Reduction in Risk of Major Thrombotic Vascular Events in PAD, Including Patients after Lower Extremity Revascularization due to Symptomatic PAD

• PO (Adults): 2.5 mg twice daily.

• When switching from warfarin to rivaroxaban, discontinue warfarin and start rivaroxaban as soon as INR <3.0 to avoid periods of inadequate anticoagulation. When switching from anticoagulants other than warfarin to rivaroxaban, start rivaroxaban 0–2 hr prior to next scheduled evening dose and omit dose of other anticoagulant. For continuous heparin, discontinue heparin and administer rivaroxaban at same time. When switching from rivaroxaban to warfarin or other anticoagulants, no data is available. May discontinue rivaroxaban and begin both parenteral anticoagulant and warfarin at time of next rivaroxaban dose.
• Discontinue at least 24 hr prior to surgery and other interventions. Restart as soon as hemostasis has been re-established.
• If rivaroxaban must be discontinued for other than bleeding, consider replacing with another anticoagulant; discontinuation increases risk of thrombotic events.
• PO: Prophylaxis of DVT following surgery: Administer 1st dose 6–10 hr after surgery, once hemostasis has been established. 10-mg tablet may be administered without regard to food; 15-mg and 20-mg tablet should be taken with food.
  • If unable to swallow tablet, 15-mg and 20-mg tablets may be crushed, mixed with applesauce, and administered immediately after mixing. Follow dose immediately with food. Tablets are stable in applesauce for up to 4 hr.
  • If administering crushed tablet via GI feeding tube, check placement of tube. Rivaroxaban is absorbed from the GI tract, not the small intestine. Suspend crushed tablet in 50 mL water and administer. Follow administration of 15-mg or 20-mg tablet immediately with food.
  • Crushed tablets are stable in water or applesauce for up to 4 hr.
  • Reduction in Risk of Stroke in Nonvalvular Atrial Fibrillation: Administer with evening meal.
  • Treatment of DVT and/or PE: Administer with food, at the same time each day.
  • Reduction in the Risk of Recurrence of DVT and/or PE in patients at continued risk for DVT and/or PE, Prophylaxis of VTE in Acutely Ill Medical Patients at Risk for Thromboembolic Complications Not at High Risk of Bleeding, or Reduction of Risk of Major Cardiovascular Events (CV Death, MI, and Stroke) in Chronic CAD or PAD: Administer without regard for food.

Xarelto

Therapeutic Classification: anticoagulants

Pharmacologic Classification: antithrombotics

• Tablets: 2.5 mg; 10 mg; 15 mg; 20 mg;

(anticoagulant effect)

†Blood levels.

• Assess for signs of bleeding and hemorrhage (bleeding gums; nosebleed; unusual bruising; black, tarry stools; hematuria; fall in hematocrit or BP; guaiac-positive stools); bleeding from surgical site. Notify health care professional if these occur. May use prothrombin concentrate complex, activated prothrombin complex concentrate or recombinant factor VIIa attempt to reverse life-threatening bleeding; efficacy and safety studies have not been done.
• Monitor patients with epidural catheters frequently for signs and symptoms of neurologic impairment (midline back pain, sensory and motor deficits [numbness, tingling, weakness in lower limbs], bowel and/or bladder dysfunction). Epidural catheter should not be removed earlier than 18 hr in young patients aged 20–45 yrs and 26 hrs in elderly patients aged 60–76 yrs after last administration of rivaroxaban; next dose should be at least 6 hr after catheter removal.

• May cause ↑ serum AST, ALT, total bilirubin, and GGT levels.
  • Monitor renal function periodically during therapy.

• Antidote is andexanet alfa; effects persist for at least 24 hr after last dose. Other agents and hemodialysis do not have a significant effect. Consider using prothrombin complex concentrate (PCC) or Factor VIIa.

• Instruct patient to take medication as directed. Take missed doses as soon as remembered that day. If taking 2.5 mg twice daily, take a single 2.5 mg dose at next scheduled dose. If taking 15 mg twice daily, may take two 15-mg tablets to achieve 30 mg daily dose, then return to regular schedule. If taking 10 mg, 15 mg, or 20 mg once daily, take missed dose immediately; do not double dose. Inform health care professional of missed doses at time of checkup or lab tests. Inform patients that anticoagulant effect may persist for 2–5 days following discontinuation. Advise patient to read the Medication Guide before starting therapy and with each Rx refill in case of changes. Caution patients not to discontinue medication early without consulting health care professional.
• Advise patient to report any symptoms of unusual bleeding or bruising (bleeding gums; nosebleed; black, tarry stools; hematuria; excessive menstrual flow) and symptoms of spinal or epidural hematoma (tingling; numbness, especially in lower extremities; muscular weakness) to health care professional immediately.
• Instruct patient not to drink alcohol or take other Rx, OTC, or herbal products, especially those containing aspirin, NSAIDs, or St. John's wort, or to start or stop any new medications during rivaroxaban therapy without advice of health care professional.
• Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breast feeding. Monitor for bleeding in fetus and/or neonate of women taking rivaroxaban during pregnancy.

• Prevention of blood clots and subsequent pulmonary emboli following knee/hip replacement surgery. Duration of treatment is 35 days for patients with hip replacement and 12 days for patients with knee replacement surgery.
• Treatment and prevention of thromboembolic events and major cardiovascular events.

NDC Code^*

• 50090- A-S Medication Solutions
  • 50090-3625- Xarelto
    • 50090-3625-0- 90 TABLET, FILM COATED in 1 BOTTLE (50090-3625-0)

• 50090- A-S Medication Solutions
  • 50090-3639- Xarelto
    • 50090-3639-0- 1 TABLET, FILM COATED in 1 KIT (50090-3639-0)

• 50090- A-S Medication Solutions
  • 50090-4468- Xarelto
    • 50090-4468-0- 90 TABLET, FILM COATED in 1 BOTTLE (50090-4468-0)

• 50090- A-S Medication Solutions
  • 50090-4469- Xarelto
    • 50090-4469-0- 90 TABLET, FILM COATED in 1 BOTTLE (50090-4469-0)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-577- XARELTO
    • 50458-577-10- 10 BLISTER PACK in 1 BOX, UNIT-DOSE (50458-577-10) > 10 TABLET, FILM COATED in 1 BLISTER PACK (50458-577-01)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-577- XARELTO
    • 50458-577-14- 14 TABLET, FILM COATED in 1 BOTTLE (50458-577-14)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-577- XARELTO
    • 50458-577-18- 180 TABLET, FILM COATED in 1 BOTTLE (50458-577-18)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-577- XARELTO
    • 50458-577-60- 60 TABLET, FILM COATED in 1 BOTTLE (50458-577-60)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-578- Xarelto
    • 50458-578-07- 7 TABLET, FILM COATED in 1 BOTTLE (50458-578-07)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-578- Xarelto
    • 50458-578-10- 10 BLISTER PACK in 1 CARTON (50458-578-10) > 10 TABLET, FILM COATED in 1 BLISTER PACK (50458-578-01)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-578- Xarelto
    • 50458-578-14- 14 TABLET, FILM COATED in 1 BOTTLE (50458-578-14)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-578- Xarelto
    • 50458-578-30- 30 TABLET, FILM COATED in 1 BOTTLE (50458-578-30)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-578- Xarelto
    • 50458-578-90- 90 TABLET, FILM COATED in 1 BOTTLE (50458-578-90)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-579- Xarelto
    • 50458-579-07- 7 TABLET, FILM COATED in 1 BOTTLE (50458-579-07)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-579- Xarelto
    • 50458-579-10- 10 BLISTER PACK in 1 CARTON (50458-579-10) > 10 TABLET, FILM COATED in 1 BLISTER PACK (50458-579-01)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-579- Xarelto
    • 50458-579-30- 30 TABLET, FILM COATED in 1 BOTTLE (50458-579-30)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-579- Xarelto
    • 50458-579-89- 1000 TABLET, FILM COATED in 1 BOTTLE (50458-579-89)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-579- Xarelto
    • 50458-579-90- 90 TABLET, FILM COATED in 1 BOTTLE (50458-579-90)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-579- Xarelto
    • 50458-579-99- 5 TABLET, FILM COATED in 1 BOTTLE (50458-579-99)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-580- Xarelto
    • 50458-580-07- 7 TABLET, FILM COATED in 1 BOTTLE (50458-580-07)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-580- Xarelto
    • 50458-580-10- 10 BLISTER PACK in 1 CARTON (50458-580-10) > 10 TABLET, FILM COATED in 1 BLISTER PACK (50458-580-01)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-580- Xarelto
    • 50458-580-30- 30 TABLET, FILM COATED in 1 BOTTLE (50458-580-30)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-580- Xarelto
    • 50458-580-90- 90 TABLET, FILM COATED in 1 BOTTLE (50458-580-90)

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-584- XARELTO
    • 50458-584-51- 1 KIT in 1 CARTON (50458-584-51) * 42 TABLET, FILM COATED in 1 BLISTER PACK * 9 TABLET, FILM COATED in 1 BLISTER PACK

• 50458- Janssen Pharmaceuticals, Inc.
  • 50458-584- XARELTO
    • 50458-584-52- 1 KIT in 1 CARTON (50458-584-52) * 42 TABLET, FILM COATED in 1 BLISTER PACK * 9 TABLET, FILM COATED in 1 BLISTER PACK

• 55154- Cardinal Health.
  • 55154-1422- Xarelto
    • 55154-1422-0- 10 BLISTER PACK in 1 BAG (55154-1422-0) > 1 TABLET, FILM COATED in 1 BLISTER PACK

• 55154- Cardinal Health.
  • 55154-1423- Xarelto
    • 55154-1423-8- 4440 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (55154-1423-8)

• 55154- Cardinal Health.
  • 55154-1424- Xarelto
    • 55154-1424-0- 10 BLISTER PACK in 1 BAG (55154-1424-0) > 1 TABLET, FILM COATED in 1 BLISTER PACK

• 55154- Cardinal Health.
  • 55154-1424- Xarelto
    • 55154-1424-8- 2070 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (55154-1424-8)