Xarelto film-coated pills 20 mg N28
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Active ingredients
Rivaroxaban
Release form
Pills
Composition
1 tab .: Micronized Rivaroxaban 20 mg. Auxiliary substances: microcrystalline cellulose - 37.5 mg, croscarmellose sodium - 3 mg, hypromellose 5cP - 3 mg, lactose monohydrate - 25.4 mg, magnesium stearate - 600 mcg, sodium lauryl sulfate - 500 mcg. : iron dye red oxide - 150 mcg, hypromellose 15cP - 1.5 mg, macrogol 3350 - 500 mcg, titanium dioxide - 350 mcg.
Pharmacological effect
Mechanism of actionRivaroxaban is a highly selective direct inhibitor of factor Xa, which has high bioavailability when taken orally. Activation of factor X to form factor Xa through the internal and external coagulation pathway plays a central role in the coagulation cascade. Pharmacodynamic effectsDose-dependent inhibition of factor Xa was observed in humans. Rivaroxaban has a dose-dependent effect on the prothrombin time and correlates well with plasma concentrations (r = 0.98) if the Neoplastin kit is used for analysis. When using other reagents, the results will differ. The prothrombin time should be measured in seconds, since the MHO is calibrated and certified only for coumarin derivatives and cannot be used for other anticoagulants. In patients with atrial fibrillation of non-valvular origin, receiving rivaroxaban for the prevention of stroke and systemic thromboembolism, 5/95-percentile for prothrombin 5 Neoplastin) 1-4 hours after taking the pill (i.e. at the maximum effect) vary from 14 to 40 seconds in patients taking 20 mg 1 time / day, and from 10 to 50 seconds in patients with renal insufficiency of patients receiving rivaroxaban for the treatment and prevention of recurrent deep vein thrombosis (DVT) and pulmonary thromboembolism (5/95-percentile for prothrombin time (Neoplastin) 2-4 hours after taking the tablet (ie at the maximum effect) vary from 17 to 32 seconds in patients taking 15 mg 2 times / day, and from 15 to 30 seconds in patients taking 20 mg 1 time / day. Also rivaroxaban increases the APTT dose-dependently and the result of HepTest; however, these parameters are not recommended for evaluating the pharmacodynamic effects of rivaroxaban. Also, if there is a clinical rationale for this,rivaroxaban concentration can be measured using a calibrated anti-factor Xa quantitative test. During the treatment period with Xarelto, blood clotting parameters are not monitored. In healthy men and women over 50, the QT interval was not affected by rivaroxaban
Pharmacokinetics
Suction Rivaroxaban is rapidly absorbed; Сmax is reached in 2-4 hours after taking the pill. The absolute bioavailability of rivaroxaban after administration at a dose of 10 mg is high (80-100%). When receiving rivaroxaban in a dose of 10 mg with food, no changes in AUC and Сmax were observed. The pharmacokinetics of rivaroxaban is characterized by moderate individual variability; individual variability (variation coefficient) ranges from 30% to 40%. When taking the drug in a dose of 20 mg on an empty stomach, a bioavailability of 66% was observed, due to a reduced degree of absorption. When taking Xarelto at a dose of 20 mg during a meal, an increase in the average AUC was noted by 39% compared with fasting, showing almost complete absorption and high bioavailability. The absorption of rivaroxaban depends on the place of release in the gastrointestinal tract. AUC and Cmax decreased by 29% and 56%, respectively, compared to taking the whole tablet, was observed when rivaroxaban granulate was released in the distal small intestine or ascending colon. The administration of rivaroxaban in the gastrointestinal tract distal to the stomach should be avoided, as this may entail a decrease in the absorption and, accordingly, the drug exposure. in water, and also entered through a gastric tube with the subsequent reception of liquid food, in comparison with reception of the whole tablet. The results demonstrated a predictable dose-dependent pharmacokinetic profile of rivaroxaban, while the bioavailability at the above indicated corresponded to that when receiving rivaroxaban in lower doses. Distribution Vd is moderate, Vss is approximately 50 liters. Metabolism When ingested, approximately 2/3 of the prescribed dose of rivaroxaban is metabolized and subsequently excreted in equal parts with urine and feces.The remaining 1/3 dose is eliminated by direct renal excretion unchanged, mainly due to active renal secretion. Rivaroxaban is metabolized by isoenzymes CYP3A4, CYP2J2, and also by mechanisms independent of the cytochrome system. The main sites of biotransformation are the oxidation of the morpholine group and the hydrolysis of amide bonds. According to data obtained in vitro, rivaroxaban is a substrate for the carrier proteins P-gp (P-glycoprotein) and Vssr (breast cancer resistance protein). The unchanged rivaroxaban is the only active compound in plasma, significant or active circulating metabolites are not detected in plasma. The release of Rivaroxaban, which has a systemic clearance of approximately 10 l / h, can be referred to as drug m substances with a low level of clearance. When removing rivaroxaban from plasma, the final T1 / 2 is 5 to 9 hours in young patients. The pharmacokinetics in special clinical situations Older patients have a higher concentration of rivaroxaban in plasma than in younger patients; the mean AUC value is approximately 1.5 times higher than the corresponding values in young patients, mainly due to the apparent decrease in total and renal clearance. When removing rivaroxaban from plasma, the final T1 / 2 in elderly patients ranges from 11 to 13 hours. In men and women, clinically significant differences in pharmacokinetics were not found. Too small or large body weight (less than 50 kg and more than 120 kg) only slightly affects plasma concentration of rivaroxaban (the difference is less than 25%). There are no data on pharmacokinetics in children. Clinically significant differences in pharmacokinetics and pharmacodynamics in patients of the Caucasian, Negroid and Asian races, as well as in Latin America tion, Japanese or Chinese ethnicity not nablyudalis.Vliyanie hepatic failure was investigated on the pharmacokinetics of rivaroxaban patients distributed into classes according to the Child-Pugh classification (according to standard procedures in clinical studies). Child-Pu's classification allows to evaluate the prognosis of chronic liver diseases, mainly cirrhosis.In patients who are scheduled for anticoagulant therapy, the most important consequence of impaired liver function is a decrease in the synthesis of blood coagulation factors in the liver. Since this indicator corresponds to only one of the five clinical / biochemical criteria that constitute the Child-Pugh classification; the risk of bleeding does not clearly correlate with this classification. Treatment of such patients with anticoagulants should be resolved regardless of the class of Child-Pugh classification. The drug Xarelto is contraindicated in patients with liver diseases with coagulopathy, which causes a clinically significant risk of bleeding. Patients with cirrhosis of the liver with mild hepatic insufficiency Child-Pugh) rivaroxaban pharmacokinetics was only slightly different from the corresponding indicators in the control group of healthy subjects (on average, elichenie rivaroxaban AUC 1.2 times). There were no significant differences in pharmacodynamic properties between the groups. In patients with cirrhosis and moderate hepatic insufficiency (Child-Pugh class B), the average AUC of rivaroxaban was significantly increased (2.3 times) compared with healthy volunteers due to significantly reduced clearance of the drug substance indicating a serious liver disease. The suppression of the activity of factor Xa was more pronounced (by 2.6 times) than in healthy volunteers. The prothrombin time is also 2.1 times higher than in healthy volunteers. Using the measurement of prothrombin time, an external coagulation pathway is estimated, including coagulation factors VII, X, V, II and I, which are synthesized in the liver. Patients with moderate hepatic insufficiency are more susceptible to rivaroxaban, which is a consequence of a closer relationship between pharmacodynamic effects and pharmacokinetic parameters, especially between concentration and prothrombin time. The data for patients with grade C liver failure are not available. In patients with renal insufficiency, an increase in rivaroxaban exposure was observed, inversely proportional to the degree of reduction in renal function, which evaluated CK. In patients with renal insufficiency with CK 80-50 ml / min, CK 49-30 ml / min and CK 29-15 ml / min, a 1.4-, 1.5-, and 1.6-fold increase in plasma concentrations of rivaroxaban was observed ( AUC), respectively, compared with healthy volunteers.The corresponding increase in pharmacodynamic effects was more pronounced. In patients with CK 80–50 ml / min, CK 49–30 ml / min and CK 29–15 ml / min, the overall inhibition of factor Xa activity increased 1.5, 1.9 and 2 times compared to healthy volunteers; The prothrombin time due to the action of factor Xa also increased by 1.3, 2.2, and 2.4 times, respectively. Data on the use of Xarelto in patients with CK 29–15 ml / min is limited, and therefore caution should be exercised when using the drug in this category of patients. Data on the use of Xarelto in patients with QA less than 15 ml / min are not available, and therefore it is not recommended to use the drug in this category of patients.
Indications
- prevention of stroke and systemic thromboembolism in patients with atrial fibrillation of non-valvular origin; - treatment of deep vein thrombosis and pulmonary embolism and prevention of recurrence of DVT and pulmonary embolism.
Contraindications
- hypersensitivity to rivaroxaban or any auxiliary components of the drug; - clinically significant active bleeding (for example, intracranial bleeding, gastrointestinal bleeding); - damage or condition associated with an increased risk of major bleeding, for example, an existing or recently transferred gastrointestinal ulcer , the presence of malignant tumors with a high risk of bleeding, recent injuries of the brain or spinal cord, surgery on the brain, spinal cord or eyes, intracranial to ovosis, diagnosed or suspected esophageal varicose veins, arteriovenous malformations, vascular aneurysms, or vascular pathology of the brain or spinal cord; - concomitant therapy with any other anticoagulants, such as unfractionated heparin, low molecular weight heparins (including enoxaparin, dalteparin) heparin derivatives (including fondaparinux), oral anticoagulants (including warfarin, apixaban, dabigatran), except when switching from or to rivaroxabanil when using nefracc ionized heparin in doses necessary to ensure the functioning of the central venous or arterial catheter - liver diseases occurring with coagulopathy,which causes a clinically significant risk of bleeding; renal failure with QC less than 15 ml / min (there are no clinical data on the use of rivaroxaban in this category of patients); ACS treatment with antiplatelet agents in patients undergoing stroke or transient ischemic attack; pregnancy; period lactation (breastfeeding period); - children and adolescents under 18 years of age (efficacy and safety for patients of this age group have not been established); - congenital lactase deficiency, intolerance lactose, glucose-galactose malabsorption (due to the presence of lactose in the composition). The drug should be used with caution: - in the treatment of patients with an increased risk of bleeding (including congenital or acquired tendency to bleeding, uncontrolled severe hypertension, gastric ulcer and duodenal ulcer in the acute phase, recent gastric ulcer and duodenal ulcer, vascular retinopathy, bronchiectasis or pulmonary hemorrhage in history); and patients with renal insufficiency (CK 49–30 ml / min) receiving simultaneously preparations that increase the concentration of rivaroxaban in the blood plasma; - when treating patients with renal insufficiency (CK 29–15 ml / min), care should be taken since the concentration of rivaroxaban in blood plasma in these patients may increase significantly (by an average of 1.6 times) and, as a result, they are at increased risk of bleeding, in patients receiving drugs affecting hemostasis (for example, NSAIDs, antiplatelet agents or other antithrombotic agents); - Xarelto is not recommended for use in patients receiving systemic treatment with antifungal drugs of the azoles group (for example, ketoconazole) or HIV protease inhibitors (for example, ritonavir). These drugs are strong inhibitors of the CYP3A4 isoenzyme and P-glycoprotein. As a result, these drugs can increase the concentration of rivaroxaban in plasma to a clinically significant level (an average of 2.6 times), which increases the risk of bleeding. Fluconazole (an antifungal drug of the azoles group), a moderate CYP3A4 inhibitor,less pronounced effect on rivaroxaban exposure and can be used simultaneously; patients with renal insufficiency with CC 15-29 ml / min or increased risk of bleeding and patients receiving concomitant systemic treatment with an antifungal drugs of the azole group or HIV protease inhibitors should be closely monitored for the timely detection of bleeding complications.
Precautionary measures
Do not exceed recommended doses.
Use during pregnancy and lactation
The efficacy and safety of using Xarelto in pregnant women has not been established. The data obtained in experimental studies in animals showed a pronounced toxicity of rivaroxaban for the maternal organism associated with the pharmacological effect of the drug (for example, complications in the form of hemorrhages) and leading to reproductive toxicity. Due to the possible the risk of bleeding and the ability to penetrate the placental barrier, rivaroxaban is contraindicated in pregnancy. An effective contraceptive method should be used during the period of treatment with Xarelto. There are no data on the use of Xarelto for treating women during breastfeeding. The data obtained in experimental studies in animals show that rivaroxaban is excreted in breast milk. Xarelto can be used only after the cancellation of breastfeeding. Studies have shown that rivaroxaban does not affect male and female fertility in rats. Research on the effect of rivaroxaban on human fertility has not been conducted.
Dosage and administration
The drug is taken orally during a meal. If the patient is not able to swallow the pill whole, Xarelto's pill can be crushed and mixed with water or liquid food, for example, apple sauce, just before taking. After taking the crushed Xarelto tablet 15 mg or 20 mg, you should immediately take a meal. The crushed Xarelto tablet can be administered via a stomach tube. The position of the probe in the gastrointestinal tract must be further coordinated with the doctor before taking the drug Xarelto.The crushed tablet should be administered through a stomach tube in a small amount of water, after which a small amount of water must be introduced in order to wash off the remnants of the preparation from the probe walls. After taking crushed Xarelto 15 mg or 20 mg pills, it is necessary to immediately take enteral nutrition. Prevention of stroke and systemic thromboembolism in patients with atrial fibrillation of non-valvular origin The recommended dose is 20 mg 1 time / day. For patients with impaired kidney function (CC 49-30 ml / min) the recommended dose is 15 mg 1 time / day. The recommended maximum daily dose is 20 mg. Xarelto therapy should be considered as a long-term treatment, carried out until the benefit of treatment exceeds the risk of possible complications. If you miss the next dose, you should immediately take Xarelto and continue to take the drug regularly the next day in accordance with the recommended regimen . Do not double the dose taken to compensate for the missed earlier. Treatment of DVT and pulmonary embolism and prevention of recurrence of DVT and TELARRECOMMENDED initial dose in the treatment of jails about DVT or pulmonary embolism is 15 mg 2 times / day for the first 3 weeks, followed by a switch to a dose of 20 mg 1 time / day for further treatment and prevention of recurrence of DVT and pulmonary embolism. The maximum daily dose is 30 mg during the first 3 weeks of treatment and 20 mg with further treatment. The duration of treatment is determined individually after carefully weighing the ratio of the benefits of treatment and the risk of bleeding. The minimum duration of the course of treatment (at least 3 months) should be based on an assessment of reversible risk factors (ie, prior surgery, trauma, period of immobilization). The decision to extend the course of treatment for a longer time is based on an assessment regarding persistent risk factors, or in the case of idiopathic DVT or pulmonary embolism. When skipping a dose, it is important to adhere to the prescribed dosage regimen. day, the patient should immediately take Xarelto to achieve a daily dose of 30 mg. Thus, two pills of 15 mg can be taken in one step.The next day, the patient should continue to take the drug regularly in accordance with the recommended regimen. If the next dose is missed with a dosage regimen of 20 mg 1 time / day, the patient should immediately take Xarelto and continue the next day to take the drug regularly in accordance with the recommended regimen. groups of patients dose adjustment depending on the patient's age (over 65 years), gender, body weight or ethnicity is not required. Xarelto is contraindicated in patients with liver diseases, with provoking coagulopathy, which causes a clinically significant risk of bleeding. Patients with other diseases of the liver are not required to change the dose. The limited clinical data available in patients with moderate-degree liver failure (class B according to the Child-Pugh classification) indicate a significant increase in the pharmacological activity of the drug. For patients with severe hepatic insufficiency (Child-Pugh class C), clinical data are not available. When Xarelto is prescribed to patients with renal insufficiency (CK 80-50 ml / min), dose adjustment is not required. In the prevention of stroke and systemic thromboembolism in patients with atrial fibrillation of non-valvular origin with renal insufficiency (CC 49-30 ml / min), the recommended dose is 15 mg 1 time / day. When treating DVT and PE, and preventing relapse of DVT and PE, in patients with renal insufficiency (RC 49–30 ml / min) dose adjustment is not required. The limited clinical data obtained from patients with renal insufficiency (CK 29–15 ml / min) show a significant increase in rivaroxaban concentrations in these patients. For treatment of this category of patients, Xarelto should be used with caution. The use of Xarelto in patients with CK less than 15 ml / min is not recommended. Transfer of patients with vitamin K antagonists (AVC) to Xarelto. ≤3.In case of THV and PE, treatment of AVK should be discontinued and treatment of Xarelto should be started with MHO ≤ 2.5. When switching patients from AVK to Xarelto, after taking Xarelto, the values of MHO will be erroneously increased.MHO is not suitable for determining Xarelto's anticoagulant activity and therefore should not be used for this purpose. Switching from Xarelto to vitamin K antagonists (AVK) There is a possibility of insufficient anticoagulant effect when switching from Xarelto to AVK. In this regard, it is necessary to provide a continuous sufficient anticoagulant effect during a similar transition with the help of alternative anticoagulants. It should be noted that Xarelto may contribute to the improvement of MHO. Patients who switch from Xarelto to AVK should simultaneously take AVK until MHO reaches ≥2. During the first two days of the transition period, a standard dose of AVK should be applied followed by a dose of AVK determined depending on the size of the MHO. Thus, during the simultaneous use of Xarelto and AVK, the MHO should be determined not earlier than 24 hours after the previous dose, but before the next dose of Xarelto. After discontinuation of Xarelto, the MHO value can be reliably determined 24 hours after the last dose. Transition from parenteral anticoagulants to Xarelto in patients receiving parenteral anticoagulants, Xarelto should be started 0-2 hours before the next scheduled parenteral administration of the drug (for example, low molecular weight heparin) or at the time of termination of continuous parenteral administration of the drug (for example, in / in the introduction of unfractionated heparin). The transition from Xarelto to parente Oral anticoagulants: Xarelto should be discontinued and the first dose of parenteral anticoagulant should be administered at the moment when the next dose of Xarelto had to be taken. Cardioversion in the prevention of stroke and systemic thromboembolism Xarelto treatment can be started or continued in patients who may require cardioversion. For cardioversion under the control of transesophageal echocardiography (ESRP-KG) in patients who have not previously received anti-coagulant therapy, to ensure adequate anticoagulation, treatment with Xarelto should begin at least 4 hours before cardioversion.
Side effects
The safety of Xarelto was evaluated in four phase III studies involving 6097 patients,underwent major orthopedic surgery on the lower extremities (total prosthetic knee or hip joint) and 3997 patients hospitalized for medical reasons who received treatment with Xarelto at a dose of 10 mg for up to 39 days, as well as in three studies of phase III treatment of venous thromboembolism, which included 4556 patients who received Xarelto in a dose of either 15 mg 2 times / day daily for 3 weeks, followed by a dose of 20 mg 1 time / day, or 20 mg 1 time / day for up to 21 months In addition, from two phase III studies, including 7750 patients, data were obtained on the safety of the drug in patients with atrial fibrillation of non-valvular origin who received at least one dose of Xarelto over a period of up to 41 months, as well as 10,225 patients with ACS treated with at least one dose of Xarelto 2.5 mg (2 times / day) or 5 mg (2 times / day) in addition to therapy with acetylsalicylic acid or acetylsalicylic acid with clopidogrel or ticlopidine, the duration of treatment is up to 31 months. The mechanism of action, the use of Xarelto may be accompanied by an increased risk of latent or apparent bleeding from any organs and tissues, which can lead to post-hemorrhagic anemia. The risk of bleeding may increase in patients with uncontrolled arterial hypertension and / or when combined with drugs that affect hemostasis. Signs, symptoms, and severity (including possible death) vary depending on the location, intensity, or duration of bleeding and / or anemia. Hemorrhagic complications can manifest weakness, pallor, dizziness, headache, shortness of breath, as well as an increase in limb volume or shock, which cannot be explained by other causes. In some cases, due to anemia, symptoms of myocardial ischemia, such as chest pain and angina, developed. When Xarelto was used, such well-known complications that were secondary to severe bleeding, such as compartment syndrome and renal failure due to hypoperfusion, were also recorded. Thus, the possibility of bleeding should be considered when assessing the condition of any patient receiving anticoagulants. Generalized data on the frequency of adverse reactions recorded for Xarelto are given below.In groups divided by frequency, undesirable effects are presented in order of decreasing severity, as follows: often: from ≥1% to less than 10% (from ≥1 / 100 to less than 1/10); infrequently: from ≥0.1% to less than 1% (from ≥1 / 1000 to less than 1/100); rarely: from ≥0.01% to less than 0.1% (from ≥1 / 10,000 to less than 1/1000); very rarely: less than 0.01% (less than 1 / 10,000). All adverse reactions that occurred during the treatment period in patients who participated in phase III clinical trials. From the hematopoietic system: often anemia (including appropriate laboratory parameters); infrequently, thrombocythemia (including elevated platelet count). * From the side of the cardiovascular system: often - marked reduction in blood pressure, hematoma; infrequently - tachycardia. From the organ of vision: often - hemorrhage in the eye (including hemorrhage into the conjunctiva). From the alimentary system: often - bleeding gums, gastrointestinal bleeding (including rectal bleeding), pain in the gastrointestinal tract, dyspepsia, nausea, constipation *, diarrhea, vomiting *; infrequently - dry mouth. Systemic disturbances and reactions at the injection site: often - fever *, peripheral edema, decreased overall muscle strength and tone (including weakness, asthenia); infrequently - deterioration of general well-being (including malaise); seldom - local edema *. From the liver: infrequently - abnormal liver function; rarely - jaundice. Research results: often - increased activity of hepatic transaminases; infrequently - increasing the concentration of bilirubin, increasing the activity of alkaline phosphatase *, increasing the activity of LDH *, increasing the activity of lipase *, increasing the activity of amylase *, increasing the activity of GGT *; rarely - an increase in the concentration of conjugated bilirubin (with a concomitant increase in the activity of ALT or without it). From the nervous system: often - dizziness, headache; infrequently - intracerebral and intracranial hemorrhage, short-term syncope. From the urogenital system: often - bleeding from the urogenital tract (including hematuria and menorrhagia **), renal failure (including increased creatinine concentration, increased urea concentration) *. From the respiratory system: often the urethra * - nosebleeds, hemoptysis. On the side of the skin and subcutaneous tissues: often - itching (including infrequent cases of generalized itching), rash,ecchymosis, skin and subcutaneous hemorrhages; infrequently - urticaria. From the immune system: rarely - allergic reactions, allergic dermatitis. From the musculoskeletal system: often - pain in the extremities *; infrequently - hemarthrosis; rarely, hemorrhage into the muscles. Systemic disturbances and reactions at the injection site: often - fever *, peripheral edema, deterioration of general well-being (including weakness, asthenia); infrequently - deterioration of general well-being (including malaise); rarely - local edema *. Injuries, poisoning and procedural complications: often - hemorrhages after the procedures (including postoperative anemia and bleeding from a wound), excessive hematoma with bruising; infrequently - discharge from a wound *; rarely - vascular pseudoaneurysm ***. * - were recorded after major orthopedic operations. ** - were recorded in the treatment of VTE as very frequent in women less than 55 years. *** - were recorded as infrequent in the prevention of sudden death and myocardial infarction in patients after acute coronary syndrome (after percutaneous interventions). During the post-registration monitoring, cases of the following adverse reactions were reported, the development of which had a temporary connection with the use of the drug Xarelto. It is impossible to estimate the frequency of occurrence of such adverse reactions in the framework of post-registration monitoring. On the immune system: angioedema, allergic edema. Within the framework of phase 3 RCTs, such undesirable effects were regarded as infrequent (from greater than 1/1000 to less than 1/100). On the liver: cholestasis, hepatitis (including hepatocellular damage). Within the framework of phase 3 RCTs, such undesirable effects were regarded as rare (from greater than 1/10 000 to less than 1/1000). On the side of the hematopoietic system: thrombocytopenia. Within the framework of phase 3 RCTs, such undesirable effects were regarded as infrequent (from greater than 1/1000 to less than 1/100). From the musculoskeletal system: the frequency is unknown - increased subfascial pressure syndrome (compartment syndrome) due to hemorrhage into muscles. From the urinary Systems: Frequency unknown - renal failure / acute renal failure due to bleeding, resulting in renal hypoperfusion.
Overdose
Rare cases of overdose have been reported with rivaroxaban up to 600 mg without bleeding or other adverse reactions. Due to limited absorption, a low level plateau is expected to develop drug concentrations without further increasing its average plasma concentration when used at doses higher than therapeutic (≥50 mg). Treatment The rivaroxaban specific antidote is unknown. In case of overdose, activated carbon can be used to reduce the absorption of rivaroxaban. Given the intense binding to plasma proteins, rivaroxaban is not expected to be eliminated during dialysis. If a patient receiving rivaroxaban has a bleeding complication, the next dose should be postponed or, if necessary, discontinued treatment with this drug. T1 / 2 rivaroxaban leaves approximately 5-13 hours. Treatment should be selected individually, in accordance with the severity and location of the bleeding. If necessary, you can use appropriate symptomatic treatment, such as mechanical compression (for example, in severe nosebleeds), surgical hemostasis with its assessment efficacy, infusion therapy and hemodynamic support, the use of blood products (erythrocyte mass or fresh frozen plasma, depending on concomitant anemia or coaguloma Patients) or platelets. If the measures listed above are not