ri-va-ROX-a-ban

Therapeutic Classification: anticoagulants

Pharmacologic Classification: antithrombotics

• 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).
• Treatment of VTE and the reduction in the risk of recurrent VTE in pediatric patients from birth to <18 years after 5 days of initial parenteral anticoagulant treatment.
• Thromboprophylaxis in pediatric patients 2 years old with congenital heart disease who have undergone the Fontan procedure.

• 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.

(anticoagulant effect)

†Plasma concentrations.

Contraindicated in:

• Hypersensitivity
• Active major bleeding
• Severe renal impairment (adults) (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 or any liver pathology resulting in altered coagulation (adults)
• PE with hemodynamic instability or requiring thrombolysis or pulmonary embolectomy
• Concurrent use of drugs that are combined P-glycoprotein (P-gp) inducers/strong CYP3A4 inducers or combined P-gp inhibitors/strong CYP3A4 inhibitors
• Triple positive antiphospholipid syndrome (↑ risk of thrombosis)
• Lactation: Lactation
• Pedi: Moderate or severe renal impairment (eGFR: <50 mL/min/1.73 m²) (children 1 yr); serum creatinine above 97.5th percentile (children <1 yr)
• Pedi: Hepatic impairment in children
• Pedi: Children <6 mo and any of the following (<37 wk of gestation at birth; <10 days of oral feeding; or <2.6 kg).

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
• Women of reproductive potential with abnormal uterine bleeding (↑ risk of uterine bleeding)
• Geri: Appears on Beers list. ↑ risk of bleeding in older adults. Avoid use for long-treatment of AF or VTE in favor of safer anticoagulant options.

CV: syncope.

Derm: blister, pruritus.

Hemat: BLEEDING.

Local: wound secretion.

MS: extremity pain, muscle spasm.

Drug-Drug:

• Concurrent use of drugs that are combined P-gp inhibitors/strong CYP3A4 inhibitors, including ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, 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 Deep Vein Thrombosis 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 Venous Thromboembolism 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 Deep Vein Thrombosis or Pulmonary Embolism

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

Reduction in Risk of Recurrent Deep Vein Thrombosis and/or Pulmonary Embolism in Patients at Continued Risk for Recurrent Deep Vein Thrombosis and/or Pulmonary Embolism

• 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 Atrial Fibrillation

• 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 Peripheral Arterial Disease, Including Patients After Lower Extremity Revascularization Due to Symptomatic Peripheral Arterial Disease

• PO (Adults): 2.5 mg twice daily.

Treatment of Venous Thromboembolism and Reduction in Risk of Recurrent Venous Thromboembolism in Pediatric Patients

• PO (Children Birth–<18 yr and 50 kg): Oral suspension or tablets: 20 mg once daily with food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (unless <2 yr with catheter-related thrombosis).
• PO (Children Birth–<18 yr and 30–49.9 kg): Oral suspension or tablets: 15 mg once daily with food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (unless <2 yr with catheter-related thrombosis).
• PO (Children Birth–<18 yr and 12–29.9 kg): Oral suspension: 5 mg twice daily with feeding or food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (unless <2 yr with catheter-related thrombosis).
• PO (Children Birth–<18 yr and 10–11.9 kg): Oral suspension: 3 mg three times daily with feeding or food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (unless <2 yr with catheter-related thrombosis).
• PO (Children Birth–<18 yr and 9–9.9 kg): Oral suspension: 2.8 mg three times daily with feeding or food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (unless <2 yr with catheter-related thrombosis).
• PO (Children Birth–<18 yr and 8–8.9 kg): Oral suspension: 2.4 mg three times daily with feeding or food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (up to 12 mo) unless <2 yr with catheter-related VTE in which duration should be 1 mo (up to 3 mo).
• PO (Children Birth–<18 yr and 7–7.9 kg): Oral suspension: 1.8 mg three times daily with feeding or food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (up to 12 mo) unless <2 yr with catheter-related VTE in which duration should be 1 mo (up to 3 mo).
• PO (Children Birth–<18 yr and 5–6.9 kg): Oral suspension: 1.6 mg three times daily with feeding or food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (up to 12 mo) unless <2 yr with catheter-related VTE in which duration should be 1 mo (up to 3 mo).
• PO (Children Birth–<18 yr and 4–4.9 kg): Oral suspension: 1.4 mg three times daily with feeding or food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (up to 12 mo) unless <2 yr with catheter-related VTE in which duration should be 1 mo (up to 3 mo).
• PO (Children Birth–<18 yr and 3–3.9 kg): Oral suspension: 0.9 mg three times daily with feeding or food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (up to 12 mo) unless <2 yr with catheter-related VTE in which duration should be 1 mo (up to 3 mo).
• PO (Children Birth–<18 yr and 2.6–2.9 kg): Oral suspension: 0.8 mg three times daily with feeding or food to be initiated after 5 days of initial parenteral anticoagulation therapy. Continue therapy for 3 mo (up to 12 mo) unless <2 yr with catheter-related VTE in which duration should be 1 mo (up to 3 mo).

Thromboprophylaxis in Pediatric Patients With Congenital Heart Disease After Fontan Procedure

• PO (Children 2 yr and 50 kg): Oral suspension or tablets: 10 mg once daily.
• PO (Children 2 yr and 30–49.9 kg): Oral suspension: 7.5 mg once daily.
• PO (Children 2 yr and 20–29.9 kg): Oral suspension: 2.5 mg twice daily.
• PO (Children 2 yr and 12–19.9 kg): Oral suspension: 2 mg twice daily.
• PO (Children 2 yr and 10–11.9 kg): Oral suspension: 1.7 mg twice daily.
• PO (Children 2 yr and 8–9.9 kg): Oral suspension: 1.6 mg twice daily.
• PO (Children 2 yr and 7–7.9 kg): Oral suspension: 1.1 mg twice daily.

• Tablets: 2.5 mg; 10 mg; 15 mg; 20 mg;
• Oral suspension: 1 mg/mL;

• 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 yr and 26 hr in elderly patients aged 60–76 yr 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 or Factor VIIa.

• When switching from warfarin to rivaroxaban, discontinue warfarin and start rivaroxaban as soon as INR <3.0 in adults and <2.5 in pediatric patients to avoid periods of inadequate anticoagulation. When switching from anticoagulants other than warfarin to rivaroxaban, for adult or pediatric patients, 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, for adult and pediatric patients currently taking rivaroxaban and transitioning to an anticoagulant with rapid onset, discontinue rivaroxaban and give 1st dose of the other anticoagulant (oral or parenteral) at the time that the next rivaroxaban dose was due. May discontinue rivaroxaban and begin both parenteral anticoagulant and warfarin at time of next rivaroxaban dose. Once rivaroxaban is discontinued, INR testing may be done reliably 24 hr after last 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.
• To ensure a therapeutic dose is maintained, monitor child’s weight and review dose regularly, especially for children below 12 kg.
• PO: Prophylaxis of DVT following surgery: Administer 1st dose 6–10 hr after surgery, once hemostasis has been established. To increase absorption, all doses should be taken with feeding or food. Do not break or split tablets.
  • 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.
  • If administering crushed tablet via nasogastric (NG) or gastric 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.
  • Oral suspension may be given through NG or gastric feeding tube. After administration, flush feeding tube with water.
  • Reduction in Risk of Stroke in Nonvalvular AF: 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 (Cardiovascular Death, MI, and Stroke) in Chronic Coronary Artery Disease or PAD: Administer without regard for food.

• Instruct patient to take medication as directed. Adults: 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. Pediatric Patients: If taken once a day, take missed dose as soon as possible once noticed, but only on the same day. If not possible, skip dose and continue with next dose as prescribed; do not take two doses to make up for a missed dose. If rivaroxaban is taken two times a day, take missed morning dose as soon as possible once it is noticed; a missed morning dose may be taken together with the evening dose. A missed evening dose can only be taken in the same evening. If rivaroxaban is taken three times a day, if a dose is missed, patient should skip missed dose and go back to the regular dosing schedule at the usual time without compensating for missed dose. If patient vomits or spits up dose within 30 min after receiving dose, give a new dose; if >30 min after dose is taken, do not readminister dose; take next dose as scheduled. If patient vomits or spits up dose repeatedly, contact child’s doctor right away. 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.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Monitor for bleeding in fetus and/or neonate of women taking rivaroxaban during pregnancy. In pregnant women, rivaroxaban should be used only if potential benefit justifies the potential risk to the mother and fetus.

• Prevention of blood clots and subsequent PE 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.

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