Rivaroxaban Tablets

The main ingredient of this product is rivaroxaban. Chemical name: 5-chloro-nitrogen-({(5S)-2-oxo-3-[-4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophene-carboxamide Chemical structure: Molecular formula: C19H18ClN3O5S Molecular weight: 435.89

This product is a white film-coated tablet.

1. For use in adult patients undergoing elective hip or knee replacement surgery to prevent venous thrombosis (VTE). 2. For use in the treatment of deep vein thrombosis (DVT) in adults to reduce the risk of DVT recurrence and pulmonary embolism (PE) after acute DVT. 3. For use in adult patients with non-valvular atrial fibrillation with one or more risk factors (e.g., congestive heart failure, hypertension, age ≥75 years, diabetes, history of stroke or transient ischemic attack) to reduce the risk of stroke and systemic embolism. There is limited data on the relative effectiveness of rivaroxaban compared with warfarin in reducing the risk of stroke and systemic embolism when the disease is well controlled with warfarin.

Rivaroxaban administration: Oral. Rivaroxaban 10 mg can be taken with or without food. Rivaroxaban 15 mg or 20 mg tablets should be taken with food. The recommended dose for preventing venous thrombosis in adult patients undergoing elective hip or knee replacement surgery is rivaroxaban 10 mg orally once daily. If the wound has stopped bleeding, the first dose should be taken between 6 and 10 hours after surgery. For patients undergoing major hip surgery, the recommended course of treatment is 35 days. For patients undergoing major knee surgery, the recommended course of treatment is 12 days. If a dose is missed, the patient should take rivaroxaban immediately and continue to take the medication once daily the next day. Treating DVT and reducing the risk of DVT recurrence and PE after acute DVT The recommended initial treatment dose for acute DVT is 15 mg twice daily for the first three weeks, followed by 20 mg once daily for maintenance treatment and to reduce the risk of DVT recurrence and PE, as shown in Table 1. Table 1 Dosing schedule of rivaroxaban tablets for DVT The duration of treatment should be determined on an individual basis after careful assessment of the benefits of treatment and the risk of bleeding. Short-term treatment (3 months) should be based on transient risk factors (e.g., recent surgery, trauma, immobilization), and long-term treatment should be based on permanent risk factors or idiopathic DVT. There is insufficient experience with the use of rivaroxaban for more than 12 months for this indication. If a dose is missed during the 15 mg twice daily treatment period (days 1-21), the patient should immediately take rivaroxaban to ensure that 30 mg of rivaroxaban is taken daily. In this case, two 15 mg tablets may be taken at once. Thereafter, the regular 15 mg twice daily dose should be continued as recommended. If a dose is missed during the 20 mg once daily treatment period (day 22 and later), the patient should immediately take rivaroxaban and then continue to take the once daily dose according to the recommended dose. The dose should not be doubled within a day to make up for the missed dose. For adult patients with non-valvular atrial fibrillation, the recommended dose to reduce the risk of stroke and systemic embolism is 20 mg once daily, which is also the maximum recommended dose. For patients with low body weight and advanced age (>75 years old), the physician may use 15 mg once daily at the discretion of the patient. When the benefits of rivaroxaban in preventing stroke and systemic embolism outweigh the risk of bleeding, long-term treatment should be given (see [Precautions]). If a dose is missed, the patient should take rivaroxaban immediately and continue to take the dose once daily the next day. The dose should not be doubled within a day to make up for the missed dose. Discontinuation of medication for surgery and other interventions If anticoagulant therapy must be stopped to reduce the risk of bleeding during surgery or other interventions, rivaroxaban must be discontinued at least 24 hours before the intervention to reduce the risk of bleeding. When deciding whether to delay an intervention until 24 hours after the last dose of rivaroxaban, the increased risk of bleeding must be weighed against the urgency of the intervention. Given the rapid onset of rivaroxaban, rivaroxaban should be resumed immediately after surgery or other interventions once adequate hemostasis is confirmed. If oral medications cannot be taken during or after surgical intervention, consider administering a parenteral anticoagulant. Dosing Options For patients who cannot swallow the tablet whole, rivaroxaban 10 mg, 15 mg, or 20 mg tablets may be crushed and mixed with applesauce immediately before administration. Food should be taken immediately after administration of the crushed rivaroxaban 15 mg or 20 mg tablet. Administration via nasogastric (NG) or gastric feeding tube: Once the position of the gastric tube in the stomach is confirmed, rivaroxaban 10 mg, 15 mg, or 20 mg tablets may also be crushed, mixed with 50 mL of water to form a suspension, and administered via NG or gastric feeding tube. Because rivaroxaban absorption depends on the site of drug release, administration in the distal part of the stomach should be avoided, as administration in the distal part of the stomach may reduce drug absorption and thus reduce drug exposure. Food should be given immediately after administration of the crushed rivaroxaban 15 mg or 20 mg tablet by enteral nutrition. Crushed 10 mg, 15 mg, or 20 mg rivaroxaban tablets are stable in water or applesauce for up to 4 hours. In vitro compatibility studies have shown that rivaroxaban does not adsorb from suspension to PVC or silicone nasogastric tubes. Switching from a vitamin K antagonist (VKA) to rivaroxaban For patients who are seeking to reduce the risk of stroke and systemic embolism, the VKA should be discontinued and rivaroxaban initiated when the international normalized ratio (INR) is ≤3.0. For patients seeking to treat DVT and reduce the risk of recurrent DVT and PE after acute DVT, the VKA should be discontinued and rivaroxaban initiated when the international normalized ratio (INR) is ≤2.5. When patients are switched from a VKA to rivaroxaban, the INR value can be falsely elevated but is not a valid measure of the anticoagulant activity of rivaroxaban and is therefore not recommended for use in assessing the anticoagulant activity of rivaroxaban. Switching from a vitamin K antagonist (VKA) to rivaroxaban Inadequate anticoagulation may occur during the switch from rivaroxaban to a VKA. During the transition to any other anticoagulant, adequate anticoagulation should be ensured. It should be noted that rivaroxaban can promote an increase in the INR. For patients switching from rivaroxaban to a VKA, the VKA and rivaroxaban should be used together until the INR is ≥ 2.0. The standard starting dose of the VKA should be used for the first two days of the transition period, and the VKA dose should be adjusted based on the INR test results. When patients are taking rivaroxaban and a VKA together, the INR should be measured 24 hours after the rivaroxaban dose and before the next rivaroxaban dose. After stopping rivaroxaban, a reliable INR value can be obtained at least 24 hours after the last dose. Switching from parenteral anticoagulants to rivaroxaban For patients who are receiving parenteral anticoagulants, rivaroxaban should be started 0-2 hours before the next scheduled dose if it is not continuously administered (e.g., subcutaneous low molecular weight heparin) or when it is discontinued (e.g., intravenous unfractionated heparin). Switching from rivaroxaban to a parenteral anticoagulantDiscontinue rivaroxaban and administer the first dose of a parenteral anticoagulant at the next scheduled dose of rivaroxaban.Special PopulationsPatients with renal impairmentNo dose adjustment of rivaroxaban is required in patients with mild renal impairment (creatinine clearance CrCl: 50-80 mL/min). The following doses are recommended for patients with moderate (creatinine clearance 30-49 mL/min) or severe renal impairment (creatinine clearance 15-29 mL/min):-For adult patients undergoing elective hip or knee replacement for venous thrombosis prophylaxis, no dose adjustment is required in patients with moderate renal impairment (creatinine clearance 30-49 mL/min). Avoid

The following adverse reactions are also discussed in other sections of this labeling: • Increased risk of stroke after premature discontinuation of treatment in patients with non-valvular atrial fibrillation (see [Warnings] and [Precautions]) • Risk of bleeding (see [Precautions]) • Spinal/epidural hematoma (see [Warnings] and [Precautions]) Clinical trials Due to the different conditions under which clinical trials are conducted, the incidence of adverse reactions observed in the clinical trials of a drug cannot be directly compared to the incidence observed in the clinical trials of another drug and may not reflect the incidence observed in clinical practice. During clinical development for approved indications, 16,326 patients were treated with rivaroxaban. The study included 7111 patients who received rivaroxaban 15 mg or 20 mg orally once daily for a median of 19 months (5558 for 12 months and 2512 for 24 months) to reduce the risk of stroke and systemic embolism in nonvalvular atrial fibrillation (ROCKETAF); 4728 patients who received rivaroxaban 15 mg orally twice daily for three weeks followed by 20 mg orally once daily (EINSTEINDVT, EINSTEINPE) or 20 mg orally once daily (EINSTEINExtension studies) to treat DVT, PE, and reduce the risk of recurrent DVT and PE; and 4487 patients who received rivaroxaban 10 mg orally once daily to prevent DVT after hip or knee replacement surgery (RECORD1-3). Bleeding: The most common adverse reaction with rivaroxaban is bleeding (see [Precautions]). For use in adult patients with nonvalvular atrial fibrillation to reduce the risk of stroke and systemic embolism In the ROCKETAF trial, the most common adverse reactions associated with permanent discontinuation were bleeding events, with an incidence of 4.3% in the rivaroxaban group and 3.1% in the warfarin group. The incidence of discontinuation due to non-bleeding adverse events was similar in the two treatment groups. Table 2 shows the number of patients who experienced each type of bleeding event in the ROCKETAF study. Table 2. Bleeding Events in the ROCKETAF Clinical Trial Study*• For all subtypes of major bleeding, a single bleeding event may be shown in more than one row, and a single patient may have more than one event. ✟ Defined as clinically significant bleeding associated with a decrease in hemoglobin of ≥2 g/dL, transfusion of ≥2 units of packed red blood cells or whole blood, bleeding at a major site, or with a fatal outcome. Hemorrhagic stroke was counted in both bleeding and efficacy events. The incidence of major bleeding after excluding hemorrhagic stroke was 3.3/100 patient-years in the rivaroxaban group versus 2.9/100 patient-years in the warfarin group. ✟✟The majority of events were intracerebral and included intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal events. Treating Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), and Reducing the Risk of Recurrence of DVT and PE EINSTEIN DVT and EINSTEIN PE Studies In the pooled EINSTEIN DVT and EINSTEIN PE clinical studies, the most common adverse reactions leading to permanent discontinuation were bleeding events, occurring in 1.7% of patients with rivaroxaban versus 1.5% with enoxaparin/vitamin K antagonist (VKA), respectively. The mean duration of treatment for patients receiving rivaroxaban was 208 days and for patients receiving enoxaparin/VKA was 204 days. Table 3 shows the number of patients who experienced major bleeding events in the pooled analysis of the EINSTEIN DVT and EINSTEIN PE studies. Table 3. Major Bleeding Events in the Pooled Analysis of the EINSTEIN DVT and EINSTEIN PE Clinical Trial Studies* Bleeding events occurring after randomization and up to 2 days after the last dose of study drug. Although a patient may have 2 or more events, the patient was counted only once in the same category. Treatment schedule in EINSTEIN DVT and EINSTEIN PE studies: rivaroxaban 15 mg twice daily for 3 weeks, followed by 20 mg orally once daily; enoxaparin/VKA [enoxaparin: 1 mg/kg twice daily, VKA: dose adjusted individually to achieve target INR 2.5 (range: 2.0-3.0)]. Treatment-emergent major bleeding events occurred in at least 2 subjects in any pooled treatment group. *Major bleeding resulting in a decrease in Hb ≥ 2 g/dL and/or transfusion of ≥ 2 units of whole blood or packed red blood cells, excluding fatal or major bleeding in a vital organ. EINSTEIN Extension Study In the EINSTEIN Extension clinical study, the most common adverse reactions leading to permanent discontinuation were bleeding events, which occurred in 1.8% of the rivaroxaban group compared to 0.2% of the placebo group. The average duration of treatment was 190 days for both the rivaroxaban and placebo groups. Table 4 shows the number of patients who experienced major bleeding events in the EINSTEINExtension study. Table 4. Bleeding Events in the EINSTEINExtension Clinical Trial Study* Bleeding events that occurred after randomization and up to 2 days after the last dose of study drug. Although a patient could have 2 or more events, that patient was counted only once in the same category. Treatment Plan: Rivaroxaban 20 mg once daily, matched placebo once daily. No fatal or major bleeding events occurred. Prevention of Renal Vein Thrombosis After Hip or Knee Replacement Surgery In the RECORD clinical trial, the overall incidence of adverse reactions leading to permanent discontinuation was 3.7% in the rivaroxaban group. The incidence of major bleeding events and any bleeding events observed in patients in the RECORD clinical trial are listed in Table 5. Table 5. Bleeding Events in Patients Undergoing Hip and Knee Replacement Surgery* (RECORD1-3) Bleeding events that occurred at any time after the first dose of double-blind study medication (which may be before active medication) up to 2 days after the last dose of double-blind study medication. Patients may have more than one event. Including the placebo-controlled phase of RECORD2, enoxaparin was administered at a dose of 40 mg once daily (RECORD1-3) Including major bleeding events Most major bleeding events (≥60%) occurred within the first week after surgery after rivaroxaban treatment. Other adverse reactions Non-hemorrhagic adverse reactions reported by ≥1% of patients receiving rivaroxaban in the EINSTEINExtension studies are shown in Table 6. Table 6. Other adverse reactions reported by ≥1% of patients receiving rivaroxaban in the EINSTEINExtension clinical trial studies *Adverse reactions occurring after the first dose and up to 2 days after the last dose (relative risk 1.5 for rivaroxaban versus placebo). Incidence is based on the number of patients, not the number of events. Although a patient may experience 2 or more clinical adverse reactions, the patient is counted only once in the same category. The same patient may experience events in different categories. Table 7 lists non-hemorrhagic adverse reactions reported by ≥1% of patients receiving rivaroxaban in the RECORD1-3 studies. Table 7. Other adverse reactions reported in patients treated with rivaroxaban in the RECORD1-3 clinical trials with a ≥1% incidence *Adverse reactions occurring at any time after the first double-blind dose (which may be before active drug) up to 2 days after the last dose of double-blind study drug. Including the placebo-controlled phase of RECORD2, enoxaparin was given at a dose of 40 mg once daily (RECORD1-3) Other clinical trials: In a study of medical emergency patients receiving rivaroxaban 10 mg tablets, cases of pulmonary hemorrhage and pulmonary hemorrhage with bronchiectasis were observed. Post-marketing adverse reactions The following adverse reactions were discovered after rivaroxaban was approved. Because these reactions are reported spontaneously (with an uncertain population size), their frequency and causal relationship to drug exposure cannot always be accurately assessed. Blood and lymphatic system diseases: agranulocytosis, thrombocytopenia Intestinal diseases: retroperitoneal hemorrhage Hepatobiliary diseases: jaundice, cholestasis, hepatitis (including hepatocellular damage) Immune system diseases: hypersensitivity, allergic reaction, anaphylactic shock, angioedema Nervous system diseases: cerebral hemorrhage, subdural hematoma, epidural hematoma, mild hemiparesis Skin and subcutaneous tissue: Stevens-Johnson syndrome

10mg*5 tablets

CSPC OUYI Pharmaceutical Co., Ltd.

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