Instructions for Rivaroxaban

1. Common name: Rivaroxaban

Product name:Xarelto

Full names: Rivaroxaban, Xarelto, Rivaroxaban, Xarelto

2. Indications:

1. Reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation:

Rivaroxaban reduces the risk of stroke and systemic embolism in adults with nonvalvular atrial fibrillation when well controlled on warfarin therapy.

2. Deep vein thrombosis (DVT): Rivaroxaban is suitable for the treatment of deep vein thrombosis.

3. Pulmonary embolism (PE): Rivaroxaban is suitable for the treatment of pulmonary embolism.

4. Reduce the risk of deep vein thrombosis and/or recurrence of pulmonary embolism:

Rivaroxaban is indicated to reduce the risk of recurrence of DVT and/or PE in adult patients who remain at risk for recurrence of DVT and/or PE after completing initial treatment lasting at least6 months.

5. Prevention of deep vein thrombosis after hip or knee replacement:

Rivaroxaban is indicated for the prevention of deep vein thrombosis (DVT), which may lead to pulmonary embolism in adult patients undergoing knee or hip replacement surgery.

6. Prevention of venous thromboembolism (VTE) in acutely ill patients who are at risk for thromboembolic complications but not at high risk for bleeding:

Rivaroxaban is indicated for the prevention of venous thromboembolism and VTE-related death during hospitalization and after discharge in adult patients admitted for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe activity limitation and other risk factors for VTE but who are not at high risk for bleeding.

7. Reduce the risk of major cardiovascular events in patients with coronary heart disease:

Rivaroxaban combined with aspirin reduces the risk of major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in adults with coronary artery disease.

8.Reduced risk of major thrombotic vascular events in patients with peripheral arterial disease(PAD), including patients undergoing lower extremity revascularization for symptomatic PAD:

In adult patients withPAD, including those who have recently undergone lower extremity revascularization surgery for symptomatic PAD, rivaroxaban combined with aspirin reduces the risk of major thrombovascular events (myocardial infarction, ischemic stroke, acute limb ischemia, and major amputation of vascular etiology).

9. Treat venous thromboembolism and reduce the risk of recurrent venous thromboembolism (VTE) in pediatric patients:

Rivaroxaban is indicated for the treatment of venous thromboembolism and may reduce the risk of recurrent VTE in pediatric patients from birth to 18 years of age who receive at least 5 days of initial parenteral anticoagulation.

10. Children with congenital heart diseaseThrombus prevention after Fontan surgery:

Rivaroxaban is suitable for thromboprophylaxis in children aged 2 years and above with congenital heart disease who have undergone Fontan surgery.

3. Usage and dosage:

1. Recommended dose of rivaroxaban for adult patients:

（1) To reduce the risk of stroke in patients with non-valvular atrial fibrillation: when CrCl>50mL/min, take 20mg once a day with dinner; when CrCl≤50mL/min, take 15mg once a day with dinner.

(2) Treatment of deep vein thrombosis and/or pulmonary embolism: When CrCl ≥ 15 mL/min, take 15 mg twice a day, then transition to 20 mg once a day after 21 days; when CrCl < 15 mL/min, avoid using this drug.

(3) Reduce the risk of recurrent DVT and/or PE in patients at risk for persistent DVT and/or PE: When CrCl ≥ 15 mL/min, take 10 mg once daily after at least 6 months of standard anticoagulant therapy; when CrCl < 15 mL/min, avoid using this drug.

(4) Prevention of deep vein thrombosis after hip replacement surgery: When CrCl ≥ 15 mL/min, take a dose of 10 mg once a day 6-10 hours after hemostasis is completed for 35 days; when CrCl < 15 mL/min, avoid using this drug.

(5) Prevention of deep vein thrombosis after knee replacement surgery: When CrCl ≥ 15 mL/min, take a dose of 10 mg once a day 6-10 hours after hemostasis is completed for 12 days; when CrCl < 15 mL/min, avoid using this drug.

(6) VTE prophylaxis in acutely ill patients at risk for thromboembolic complications but not at high risk of bleeding: When CrCl ≥ 15 mL/min, take a dose of 10 mg once daily during hospitalization and for 31-39 days after discharge; avoid using this drug when CrCl < 15 mL/min.

(7) Reduce the risk of major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in coronary heart disease: No dose adjustment is required based on CrCl, 2.5 mg twice daily plus once daily aspirin (75-100 mg).

(8) Reduce the risk of major thrombovascular events in PAD, including patients after lower extremity revascularization for symptomatic PAD: No dose adjustment is required based on CrCl, 2.5 mg twice daily plus once daily aspirin (75-100 mg). When starting treatment after successful lower extremity revascularization surgery, start treatment as soon as hemostasis is established.

2. Recommended dosage of rivaroxaban in pediatric patients: 1mg Rivaroxaban tablets=1mL suspension

(1) For the treatment and reduction of risk of recurrent VTE in pediatric patients from birth to under 18 years of age:

Oral suspension:Patients 2.6-2.9kg take 0.8mg three times a day; patients 3-3.9kg take 0.9mg three times a day; patients 4-4.9kg take 1.4mg three times a day; patients 5-6.9kg take 1.6 three times a day mg; patients 7-7.9kg take 1.8mg three times a day; patients 8-8.9kg take 2.4mg three times a day; patients 9-9.9kg take 2.8mg three times a day; patients 10-11.9kg take 3mg three times a day; patients 12-29.9kg take 5mg twice a day. Oral suspension or tablet: Patients 30-49.9 kg take 15 mg once daily; patients ≥50 kg take 20 mg once daily.

Notes:1. Start treatment with rivaroxaban at least 5 days after initial parenteral anticoagulation therapy. Patients younger than 6 months of age must be at least 37 weeks pregnant at birth, have been fed orally for at least 10 days, and weigh ≥2.6kg at the time of administration. To increase absorption, all doses should be taken with feeding or food.

2. All pediatric patients (except patients <2 years of age with catheter-related thrombosis): Children with thrombosis should continue to receive rivaroxaban for at least 3 months. When clinically necessary, treatment can be extended to 12 months. The benefit of continued treatment beyond 3 months should be assessed on an individual basis, taking into account the risk of recurrent thrombosis and the potential risk of bleeding.

3. Pediatric patients <2 years old with catheter-related thrombosis: For children <2 years old with catheter-related thrombosis, rivaroxaban treatment should be continued for at least 1 month. When clinically necessary, treatment can be extended to 3 months. The benefit of continued treatment beyond 1 month should be assessed on an individual basis, taking into account the risk of recurrent thrombosis and the potential risk of bleeding.

(2) Thrombosis prevention after Fontan surgery in children with congenital heart disease:

Oral suspension:Patients 7-7.9kg take 1.1mg twice a day; patients 8-9.9kg take 1.6mg twice a day; patients 10-11.9kg Take 1.7mg three times a day; patients 12-19.9kg take 2mg twice a day; patients 20-29.9kg take 2.5mg twice a day; patients 30-49.9kg take 7.5mg once a day. Oral suspension or tablets: Patients ≥50 kg take 10 mg once daily.

3. Stop surgery and other interventions:

If anticoagulant therapy must be discontinued to reduce the risk of bleeding during surgery or other procedures, rivaroxaban should be discontinued at least 24 hours before surgery to reduce the risk of bleeding. When deciding whether to delay surgery until 24 hours after the last dose of rivaroxaban, the increased risk of bleeding should be weighed against the urgency of intervention. After surgery or other procedures, rivaroxaban should be restarted once hemostasis has been achieved, taking into account the short onset of action. If oral medications cannot be taken during or after surgery, injectable anticoagulants may be considered.

4. Adverse reactions:

The most common side effects of rivaroxaban are bruising and bleeding in various parts of the body, anemia, dizziness, headache, low blood pressure, stomach and abdominal pain, indigestion, nausea, constipation, diarrhea, vomiting, itching, rash, arm and leg pain, decreased kidney function, fever, peripheral edema, decreased general strength and energy, elevated levels of certain liver enzymes in the blood, and leakage of blood or fluid from surgical wounds.

5. Storage:

RivaroxabanTablets, granules and reconstituted suspensions should be stored at room temperature of 20-25°C (68-77°F); tolerances are allowed between 15-30°C (59-86°F). Do not freeze granules or reconstituted suspension. Suspension must be used within 60 days.

6. Taboo:

Rivaroxaban is contraindicated in patients with active pathological bleeding and severe allergic reactions to Rivaroxaban and its components.

7. Mechanism of action:

RivaroxabanisSelective inhibitor of FXa. Its activity does not require cofactors (such as antithrombin III). Rivaroxaban inhibits free FXa and prothrombinase activity. Rivaroxaban has no direct effect on platelet aggregation, but indirectly inhibits thrombin-induced platelet aggregation. By inhibiting FXa, rivaroxaban reduces thrombin generation.