Product Overview
[Drug Name]
Generic Name: Rivaroxaban Tablets
Trade Name: Ruizhitan Rivaroxaban Tablets 10mg x 20 Tablets
[Main Ingredient]
Rivaroxaban.
[Properties]
This product is a pink film-coated tablet that appears white to 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) in adults to reduce the risk of DVT recurrence and pulmonary embolism (PE) after acute DVT. 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).
[Specifications]
10mg x 20 tablets
[Dosage and Administration]
1. The recommended dose is rivaroxaban 10mg orally once daily. times. If the wound has stopped bleeding, the first dose should be taken between 6 and 10 hours after surgery. The length of treatment depends on each patient's risk of venous thromboembolism, which is determined by the type of orthopedic surgery they undergo. 2. For patients undergoing major hip surgery, a 5-week treatment course is recommended. For patients undergoing major knee surgery, a 2-week treatment course is recommended. If a dose is missed, the patient should immediately take rivaroxaban and continue taking it once daily the following day. Patients can take rivaroxaban with meals or without meals.
[Adverse Reactions]
The safety and efficacy of rivaroxaban 10 mg have been evaluated in three Phase III studies. In these three studies, a total of 4,571 patients undergoing major lower limb orthopedic surgery (total hip replacement or total knee replacement) received rivaroxaban treatment for up to 39 days. A total of approximately 14% of the treated patients experienced adverse reactions. Bleeding and anemia occurred in approximately 3.3% and 1% of the patients, respectively. Other common adverse reactions include nausea, increased GGT, and increased transaminases. Adverse reactions should be explained in the context of surgery. Due to its pharmacological mode of action, rivaroxaban may cause an increased risk of occult or overt bleeding in some tissues or organs, which may lead to anemia after bleeding. Due to different sites, degrees or ranges of bleeding, the signs and symptoms of bleeding may vary. The symptoms and severity (including possible fatal outcomes) of bleeding may vary. The risk of bleeding may be increased in certain patient groups, such as patients with uncontrolled severe arterial hypertension and/or patients taking other drugs that affect hemostasis. Bleeding complications may manifest as weakness, asthenia, pallor, dizziness, headache or unexplained swelling. Therefore, the possibility of bleeding should be considered when evaluating patients taking anticoagulants. Table 1 below lists adverse reactions from the three phase studies according to system organ class (MedDRA) and frequency of occurrence. Frequency definitions are as follows: Common: >21/100 to <1/10. Uncommon: ≥1/1,000 to <1/100. Rare: >≥1/10,000 to <1/1,000. Unknown: No estimate can be made based on available data.
[Contraindications]
1. Patients with hypersensitivity to rivaroxaban or any of the excipients in the tablets. 2. Patients with clinically significant active bleeding should not use rivaroxaban tablets. 3. Patients with liver disease with coagulation abnormalities and a risk of clinically relevant bleeding. 4. Pregnant and lactating women.
[Drug Interactions]
See the package insert for details.
[Precautions]
See the package insert for details.
[Pediatric Use]
Due to the lack of safety and efficacy data, rivaroxaban tablets are not recommended for use in adolescents or children under 18 years of age.
[Elderly Use]
No dose adjustment is required for elderly patients (>65 years of age).
[Overdose]
1. Absorption: The absolute bioavailability of a 10 mg dose of rivaroxaban is high (80%-100%). Rivaroxaban is rapidly absorbed, reaching maximum concentration (Cmax) 2-4 hours after administration. Food has no significant effect on the AUC or Cmax of a 10 mg rivaroxaban tablet, so the timing of administration of a 10 mg tablet is not restricted by meals. The pharmacokinetics of rivaroxaban are generally linear up to a dose of approximately 15 mg once daily. At higher doses, rivaroxaban exhibits dissolution-limited absorption, with bioavailability and absorption decreasing with increasing dose. This phenomenon is more pronounced in the fasted state than in the fed state. Rivaroxaban pharmacokinetics show moderate variability, with inter-individual variability (CV%) ranging from 30% to 40%, but variability is higher (70%) in exposure on the day of surgery and the first postoperative day. 2. Distribution: Rivaroxaban is highly bound to plasma proteins (primarily serum albumin), approximately 92% to 95% in humans. The volume of distribution is moderate, with a steady-state volume of distribution of approximately 50 liters. 3. Metabolism and elimination: (1) About 2/3 of the dose of rivaroxaban is metabolized and degraded, and then half is excreted through the kidneys and the other half is excreted through the feces. The remaining 1/3 of the dose is excreted directly through the kidneys in the urine in the form of the active drug prototype, mainly through active secretion by the kidneys. (2) Rivaroxaban is metabolized by CYP3A4, CYP2J2 and CYP-independent mechanisms. Oxidative degradation of the morpholinone moiety and hydrolysis of the amide bond are the main biotransformation sites. In vitro studies have shown that rivaroxaban is a substrate for the transport proteins P-gp (P-glycoprotein) and Bcrp (breast cancer resistance protein). (3) The rivaroxaban prototype is the most important compound in human plasma, and no major or active circulating metabolites have been found. The systemic clearance of rivaroxaban is approximately 10 L/h, making it a low-clearance drug. The elimination half-life after intravenous administration of 1 mg is approximately 4.5 hours. The clearance rate after oral administration of 10 mg is limited by the absorption rate, with an average elimination half-life of 7 to 11 hours. 4. Elderly use (>65 years)/gender: Elderly patients have higher plasma concentrations than younger patients, with average AUC values approximately 1.5 times that of younger patients, mainly due to (significantly) reduced total clearance and renal clearance in elderly patients. No dose adjustment is required. There are no gender differences in pharmacokinetics and pharmacodynamics. 5. Body weight differences: Extreme body weight (<50 kg or >120 kg) has only a slight effect (less than 25%) on the plasma concentration of rivaroxaban, and no dose adjustment is required. 6. Racial differences: No clinically significant racial differences in the pharmacokinetics and pharmacodynamics of rivaroxaban were observed in Caucasian, African American, Hispanic, Japanese or Chinese patients.
[Pharmacology and Toxicology]
1. Pharmacological action (1) Rivaroxaban is an oral drug that is highly selective and directly inhibits factor Xa. By inhibiting factor Xa, rivaroxaban can interrupt the intrinsic and extrinsic pathways of the coagulation cascade, inhibiting the generation of thrombin and thrombus formation. Rivaroxaban does not inhibit thrombin (activated factor I) and has not been shown to have an effect on platelets. (2) In humans, rivaroxaban has been observed to inhibit factor Xa activity in a dose-dependent manner. The effect of rivaroxaban on prothrombin time (PT) is dose-dependent and closely correlated with plasma concentrations when measured with NeopLastin® (correlation coefficient 0.98). Different results may be obtained using other reagents. The PT should be read within seconds because the international normalized ratio (INR) is only calibrated and validated for coumarins and cannot be used for other anticoagulants. In patients undergoing major orthopedic surgery, 2-4 hours after taking the tablet (when the effect is strongest), the PT of the 5/95th percentile is (NeopLastin®) 13-25 seconds (baseline value before surgery is 12-15 seconds). 3) Activated partial thromboplastin time (aPTT) and HepTest duration are also dose-dependent; however, they are not recommended for evaluating the efficacy of rivaroxaban. Rivaroxaban also has an effect on factor Xa activity, however, there is currently no calibration standard. Monitoring of coagulation parameters is not required during routine clinical use of rivaroxaban. 2. Toxicological studies (1) Based on traditional safety pharmacology, single-dose toxicity, phototoxicity, and genotoxicity studies, non-clinical data showed no special harm to humans. The effects observed in repeated-dose toxicity studies were mainly due to the extended pharmacodynamic activity of rivaroxaban. In rats, increased IgG and IgA blood concentrations were observed at clinically relevant blood concentrations. (2) Animal studies have shown reproductive toxicity related to the pharmacological mechanism of action of rivaroxaban (e.g., bleeding complications). Embryo-fetal toxicity (post-implantation loss, delayed/progressive ossification, multiple light-colored spots on the liver) and increased incidence of common malformations and placental changes were observed at clinically relevant blood concentrations. In prenatal and postnatal studies in rats, reduced offspring viability was observed at doses that were maternally toxic.
