利伐沙班说明书

Rivaroxaban is indicated for the prevention of venous thrombosis (VTE) in adult patients undergoing elective hip or knee replacement surgery.

[Usage and Dosage] The recommended dose is 10 mg of oral rivaroxaban, once daily. If the wound has stopped bleeding, the first medication should be administered between 6-10 hours after surgery. The length of treatment is determined by each patient's risk of VTE, i.e. by the type of orthopedic surgery the patient has undergone. For patients undergoing major hip surgery, a recommended course of treatment is 5 weeks. For patients undergoing major knee surgery, a recommended course of treatment is 2 weeks. If a missed dose occurs, the patient should take rivaroxaban immediately and continue taking the drug once a day the next day. Patients can take rivaroxaban with a meal or on its own.

【Notes】

Risk of Bleeding: As detailed below, some subgroups of patients are at higher risk of bleeding. After initiation of treatment, these patients should be monitored closely for signs of bleeding complications. This can be accomplished by regular physical examination of the patient, close observation of surgical wound drainage, and regular determination of hemoglobin. Any unexplained decrease in hemoglobin or blood pressure should prompt a search for the site of bleeding.

Renal Impairment: In patients with severe renal impairment (creatinine clearance <30 mL/min), the plasma concentration of rivaroxaban may be significantly elevated, resulting in an increased risk of bleeding. Rivaroxaban is not recommended for patients with creatinine clearance <15 mL/min. Rivaroxaban should be used with caution in patients with creatinine clearance 15-29 mL/min. Rivaroxaban should be used with caution in patients with moderate renal impairment (creatinine clearance 30-49 mL/min) when used concomitantly with other drugs that may increase rivaroxaban plasma concentrations.

Hepatic Impairment: In cirrhotic patients with moderate hepatic impairment (Child Pugh B category), rivaroxaban plasma concentrations may be significantly elevated, resulting in an increased risk of bleeding. Rivaroxaban is contraindicated in patients with liver disease associated with coagulation abnormalities and clinically relevant risk of bleeding. Rivaroxaban can be used with caution in cirrhotic patients with moderate hepatic impairment (Child Pugh B category) if they are not accompanied by coagulation abnormalities.

Interactions with other drugs: Concomitant use of rivaroxaban is not recommended in patients receiving systemic azole-antifungal agents (e.g., ketoconazole, itraconazole, voriconazole, and posaconazole) or HIV protease inhibitors (e.g., ritonavir). These active substances are potent inhibitors of CYP3A4 and P-gp and, therefore, may increase rivaroxaban plasma concentrations and cause a clinically relevant increase in the risk of bleeding. Fluconazole is considered to have a small effect on rivaroxaban plasma concentrations and can be coadministered with caution. Use caution in patients receiving concomitant medications that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, platelet aggregation inhibitors, or other antithrombotic agents.

Other Bleeding Risks: As with other antithrombotic agents, rivaroxaban should be used with caution in patients with the following bleeding risks: congenital or acquired bleeding disorder, uncontrolled severe arterial hypertension, active gastrointestinal ulcerative disease, recent gastrointestinal ulcer, vasogenic retinopathy, recent intracranial or intracerebral hemorrhage, intraspinal or intracerebral vascular abnormalities, recent brain, spine, or ophthalmic surgery.

Hip fracture surgery: For these patients, hip fracture surgery is treated with rivaroxaban. Evidence-based studies, such as clinical trials of efficacy and safety, have not yet been conducted. There is no evidence to recommend the use of rivaroxaban in these patients.

Spinal/epidural anesthesia or puncture: When axonal anesthesia (spinal/epidural anesthesia) or spinal/epidural puncture is used, patients receiving antithrombotic drugs to prevent thrombotic complications are at risk for epidural or spinal hematoma, which may lead to long-term or permanent paralysis. Postoperative use of an indwelling epidural catheter or concomitant use of drugs that affect hemostasis may increase the risk of the above events. Trauma or repeated epidural or spinal taps may also increase the risk. Patients should be monitored frequently for signs and symptoms of neurological impairment (eg, numbness or weakness in the legs, bowel or bladder dysfunction). If neurological impairment is observed, immediate diagnosis and treatment are necessary. Physicians should weigh the potential benefits and risks before performing axonal intervention in patients receiving anticoagulation and in patients receiving anticoagulation for thromboprophylaxis programs.

Effects on ability to drive and use machinery: There have been no studies on the effects on the ability to drive and use machinery. There have been reports of syncope and dizziness after surgery, which may affect the ability to drive and use machinery, but reports indicate that these adverse reactions are uncommon. Patients experiencing these adverse reactions should not drive or use machinery. No clinically significant interactions with food were observed. Laboratory Parameters: As expected, coagulation parameters (eg, PT, aPTT, HepTest) were affected by the mode of action of rivaroxaban.

[Pediatric Use] Due to the lack of safety and efficacy data, rivaroxaban is not recommended for use in adolescents or children under 18 years of age.

[Dose for Elderly Patients] No dose adjustment is required for elderly patients (>65 years old).

[Usage in Pregnant and Lactating Women] Pregnant women: There are no sufficient data on the use of rivaroxaban in pregnant women. Animal studies have shown reproductive toxicity. Rivaroxaban is contraindicated in pregnant women due to potential reproductive toxicity, inherent risk of bleeding, and the fact that rivaroxaban can cross the placenta. Women of childbearing potential should use contraception during treatment with rivaroxaban. Lactation: There are no data on the use of rivaroxaban in lactating women. Data from animal studies indicate that rivaroxaban passes into breast milk. Rivaroxaban is therefore contraindicated in lactating women. A decision must be made whether to discontinue breastfeeding or rivaroxaban treatment.

[Contraindications] Patients who are allergic to rivaroxaban or any excipients in the tablets; patients with clinically significant active bleeding; patients with liver disease who have coagulation abnormalities and clinically relevant bleeding risks; pregnant and lactating women are contraindicated.