SALUBRIS Rivaroxaban Tablets For Venous Thrombosis 10mg*28

[Drug Name]
Generic Name: Rivaroxaban Tablets
Trade Name: Xinlitai Rivaroxaban Tablets 10mg x 28 Tablets

[Main Ingredients]
Main Ingredient: Rivaroxaban. Chemical Name: 5-Chloro-nitro-({(5S)-2-oxo-3-[-4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophene-carboxamide. Molecular Formula:
C19H18CIN3O5S. Molecular Weight: 435.89

[Properties]
This product is a film-coated tablet that appears white or off-white after removal of the coating.

[Indications/Main Functions]
1. For the prevention of venous thrombosis (VTE) in adult patients undergoing elective hip or knee replacement surgery. 2. For the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in adults; for reducing the risk of recurrent DVT and/or PE in patients whose risk persists after completing at least 6 months of initial treatment. (For patients with hemodynamically unstable PE, see [Precautions]). 3. For the reduction of the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation and one or more risk factors (e.g., congestive heart failure, hypertension, age ≥75 years, diabetes, history of stroke or transient ischemic attack). Limited data are available on the relative effectiveness of rivaroxaban compared with warfarin in reducing the risk of stroke and systemic embolism, provided the condition is well controlled on warfarin.

[Specifications]
10mg x 28 tablets

[Dosage and Administration]
Rivaroxaban administration: Oral. Rivaroxaban 10mg can be taken with or without food. Rivaroxaban 15mg or 20mg tablets should be taken with food. For the prevention of venous thrombosis in adult patients undergoing elective hip or knee replacement surgery: The recommended dose is rivaroxaban 10 mg taken orally once daily. If wound bleeding has stopped, 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, patients should take rivaroxaban immediately and continue taking it once daily the following day. For the treatment of deep vein thrombosis (DVT) and periarthritis (PE), and to reduce the risk of recurrent DVT and PE, the recommended initial dose for the treatment of acute DVT or PE is 15 mg twice daily for the first three weeks; after the initial treatment period, the recommended dose for subsequent treatment is 20 mg taken orally once daily, administered approximately at the same time each day. For patients with DVT or PE caused by significant transient risk factors (e.g., recent major surgery or trauma), short-term treatment (at least three months) should be considered. Longer-term treatment should be considered for patients with DVT or PE due to causes other than significant transient risk factors, patients with unprovoked DVT or PE, or patients with a history of recurrent DVT or PE. For patients at persistent risk of DVT and/or PE after completing at least 6 months of standard anticoagulant therapy, rivaroxaban 10 mg orally once daily is recommended to reduce the risk of recurrent DVT and/or PE. For patients at high risk of recurrent DVT or PE (e.g., those with complex comorbidities, or those who experience recurrent DVT or PE while receiving rivaroxaban 10 mg once daily), rivaroxaban 20 mg once daily should be considered. Treatment duration and dose selection should be determined on an individual basis after careful assessment of treatment benefits versus bleeding risks (see Precautions). See Table 1 for details. (For other details, see the package insert.)

[Adverse Reactions]
See the package insert for details.

[Contraindications]
Rivaroxaban is contraindicated in the following patients: 1. Patients with hypersensitivity to rivaroxaban or any of the excipients in the tablets. 2. Patients with clinically significant active bleeding. 3. Lesions or conditions with a significant risk of major bleeding, such as current or recent gastrointestinal ulcers, malignant tumors with a high bleeding risk, recent brain or spinal cord injury, recent brain, spinal cord, or ophthalmic surgery, recent intracranial hemorrhage, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms, or major intraspinal or intracerebral vascular malformations. 4. Except in special circumstances for switching anticoagulants or administering unfractionated heparin (UFH) at doses required to maintain central venous or arterial catheter patency, concomitant treatment with any other anticoagulants, such as UFH, low molecular weight heparins (enoxaparin, dalteparin, etc.), biologic heparin (fondaparinux, etc.), and oral anticoagulants (warfarin, apixaban, dabigatran, etc.), is contraindicated. 5. Patients with liver disease associated with coagulation abnormalities and clinically relevant bleeding risk, including patients with Child-Pugh class B and C cirrhosis. 6. Pregnant and lactating women.

[Precautions]
Close observation is recommended throughout anticoagulant therapy. Premature discontinuation of rivaroxaban increases the risk of thromboembolic events.
Premature discontinuation of any oral anticoagulant, including rivaroxaban, in the absence of adequate alternative anticoagulant therapy increases the risk of thromboembolic events. In clinical trials, an increased incidence of stroke was observed during the conversion of patients with nonvalvular atrial fibrillation from rivaroxaban to warfarin. If premature discontinuation of rivaroxaban is necessary due to pathological bleeding or reasons other than completion of treatment, consider administering an alternative anticoagulant.
Bleeding Risk
Rivaroxaban increases the risk of bleeding, potentially resulting in serious or fatal bleeding. The risk of thromboembolic events must be weighed against the risk of bleeding when deciding whether to administer rivaroxaban to patients at increased bleeding risk.
As with other anticoagulants, patients taking rivaroxaban should be carefully observed for signs of bleeding. Caution is recommended in settings with a high risk of bleeding. If severe bleeding occurs, rivaroxaban must be discontinued. In clinical studies, patients receiving long-term rivaroxaban therapy experienced more mucosal bleeding (i.e., epistaxis, gingival bleeding, gastrointestinal bleeding, and genitourinary bleeding) and anemia compared to patients receiving VKA therapy. Therefore, in addition to adequate clinical observation, appropriate interpretation of laboratory hemoglobin/hematocrit test results can help detect occult bleeding and quantify overt bleeding and determine its clinical relevance.
For patients at increased risk of bleeding, close monitoring for bleeding complications and signs and symptoms of anemia is necessary after treatment initiation. For the postoperative population, prompt detection of bleeding can be achieved through regular physical examinations, close monitoring of surgical wound drainage, and periodic hemoglobin measurement.
Any unexplained decrease in hemoglobin or blood pressure should prompt investigation for the source of bleeding.
Signs and symptoms of blood loss should be promptly evaluated, and the need for blood replacement therapy should be considered. Rivaroxaban should be discontinued in patients with active pathological bleeding. The terminal elimination half-life of rivaroxaban is 5 to 9 hours in healthy subjects aged 20 to 45 years. Concomitant use of other medications that affect hemostasis may increase the risk of bleeding. These include aspirin, P2Y12 platelet inhibitors, other antithrombotic agents, fibrinolytics, and nonsteroidal anti-inflammatory drugs (NSAIDs). Concomitant use of combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole and ritonavir) increases rivaroxaban exposure and may increase the risk of bleeding. Although routine exposure monitoring is not necessary during rivaroxaban therapy, in certain situations, such as overdose and emergency surgery, rivaroxaban levels can be measured using a standard anti-factor Xa assay, and knowledge of rivaroxaban exposure can aid clinical decision-making. Reversal of Anticoagulant Effects There are no specific antagonists for rivaroxaban. Due to its high binding to plasma proteins, rivaroxaban is not expected to be dialyzable. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban. Partial reversal of prolonged prothrombin time has been observed in healthy subjects following administration of prothrombin complex concentrate (PCC). The use of other procoagulant reversal agents, such as activated prothrombin complex concentrate (APCC) or recombinant factor VIIa (rFVIIa), has not been evaluated in trials. See [Overdose].
Spinal Puncture/Epidural Anesthesia
Patients receiving antithrombotic medications for prophylaxis of thrombotic complications during epidural anesthesia or spinal puncture are at risk for epidural or spinal hematomas, which may result in long-term or permanent paralysis.
Postoperative use of an indwelling epidural catheter or concomitant use of medications that affect hemostasis may increase the risk of these events. Trauma or repeated epidural or spinal punctures may also increase the risk. Patients should be observed frequently for signs and symptoms of neurologic impairment, such as back pain, sensory or motor deficits (numbness, tingling, or weakness in the lower extremities), or bowel or bladder dysfunction. If neurologic impairment is observed, prompt diagnosis and treatment are essential. For patients receiving anticoagulant therapy or those planned to receive anticoagulant therapy for thromboprophylaxis, physicians should weigh the potential benefits and risks before performing a spinal puncture/epidural anesthesia. There is no clinical experience with the use of rivaroxaban 15mg and 20mg in these settings.
To minimize the potential bleeding risk associated with concomitant use of rivaroxaban with epidural anesthesia, spinal anesthesia/analgesia, or spinal puncture, the pharmacokinetic profile of rivaroxaban should be considered. The optimal time to place or remove an epidural catheter or perform a lumbar puncture is when the anticoagulant effect of rivaroxaban is low; however, the exact timing of achieving a sufficiently low anticoagulant effect in each patient is unknown. For epidural catheter removal, based on general pharmacokinetic properties, removal should be delayed for at least twice the half-life of the catheter, meaning at least 18 hours after the last dose of rivaroxaban in younger patients and at least 26 hours after the last dose of rivaroxaban in older patients. Rivaroxaban should be administered at least 6 hours after catheter removal. If an invasive puncture is performed, rivaroxaban administration should be delayed for 24 hours. Renal Impairment
Prevention of venous thrombosis in adult patients undergoing elective hip or knee replacement surgery
Avoid the use of rivaroxaban in patients with a CrCl <30 mL/min due to the expected increase in rivaroxaban exposure and enhanced pharmacodynamic effects in this patient population. Closely observe and promptly evaluate patients with a CrCl 30-50 mL/min for any signs and symptoms of blood loss. Patients who develop acute renal failure while taking rivaroxaban must discontinue treatment.
Treatment of DVT and PE to reduce the risk of recurrent DVT and PE
Avoid the use of rivaroxaban in patients with a CrCl <30 mL/min due to the expected increase in rivaroxaban exposure and enhanced pharmacodynamic effects in this patient population.
For adult patients with nonvalvular atrial fibrillation to reduce the risk of stroke and systemic embolism
Avoid the use of rivaroxaban in patients with a CrCl <15 mL/min due to increased drug exposure. Assess renal function regularly as clinically indicated (i.e., more frequently if renal function may be diminished) and adjust therapy accordingly. If acute renal failure occurs during rivaroxaban use, consider dose adjustment or discontinuation.
Interactions with Other Drugs
Concomitant use of rivaroxaban is not recommended in patients taking systemic medications such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (e.g., ritonavir). Because these drugs are potent inhibitors of CYP3A4 and P-gp, concomitant use may result in clinically significant increases in rivaroxaban plasma concentrations (average 2.6-fold), increasing the risk of bleeding.
Caution is advised in patients taking concomitant medications that affect hemostasis (e.g., NSAIDs, acetylsalicylic acid (ASA), platelet aggregation inhibitors, or selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs)). Appropriate prophylactic therapy should be considered in patients at risk for developing ulcerative gastrointestinal disease. Other Bleeding Risks
As with other antithrombotic drugs, rivaroxaban is not recommended in patients with the following elevated bleeding risks: congenital or acquired bleeding disorders; uncontrolled severe hypertension; other gastrointestinal disorders without active ulcers that may lead to bleeding complications (e.g., inflammatory bowel disease, esophagitis, gastritis, and gastroesophageal reflux disease); vasculogenic retinopathy; or a history of bronchiectasis or pulmonary hemorrhage.
Venous Thromboembolism Prevention in Hip Fracture Surgery
No interventional clinical studies have evaluated the efficacy and safety of rivaroxaban in patients undergoing hip fracture surgery.
Patients with Prosthetic Heart Valves
The safety and efficacy of rivaroxaban have not been studied in patients with prosthetic heart valves; therefore, there are no data to support that rivaroxaban provides adequate anticoagulation in this patient population. Rivaroxaban is not recommended for use in such patients. Patients with Hemodynamically Unstable PE or Those Requiring Thrombolysis or Pulmonary Embolectomy
Rivaroxaban is not recommended as an alternative to unfractionated heparin for patients with hemodynamically unstable PE who may require thrombolysis or pulmonary embolectomy, as its safety and efficacy have not been studied in these clinical settings.
Dosage Recommendations Before and After Invasive Procedures and Surgeries (Except Elective Hip or Knee Replacement Surgery)
If an invasive procedure or surgery is required, rivaroxaban should be discontinued for at least 24 hours before the intervention, as appropriate and based on the physician's clinical judgment.
If the procedure cannot be postponed, the increased risk of bleeding should be weighed against the urgency of the intervention.
After the invasive procedure or surgery, rivaroxaban should be resumed as soon as clinically possible and adequate hemostasis has been achieved.
Ingredient Information
Rivaroxaban tablets contain lactose. Patients with rare hereditary conditions such as lactose or galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medication.
Effects on Ability to Drive and Use Machinery
Rivaroxaban has minimal effects on the ability to drive and use machinery.
Adverse reactions such as syncope (frequency: rare) and dizziness (frequency: common) have been reported. Patients experiencing these adverse reactions should not drive or operate machinery.