Xarelto pills 10mg, 30pcs

Composition

1 film coated tablet contains: Active ingredient: rivaroxaban micronized – 10 mg; excipients: microcrystalline cellulose-40 mg, croscarmellose sodium-3 mg, hypromellose 5 cP-3 mg, lactose monohydrate-27.90 mg, magnesium stearate-0.60 mg, sodium lauryl sulfate-0.50 mg; shell: iron oxide red dye – 0.015 mg, hypromellose 15 cP-1,500 mg, macrogol 3350-0.500 mg, titanium dioxide-0.485 mg

Pharmacological action

Rivaroxaban is a highly selective direct factor Xa inhibitor with high oral bioavailability. Activation of factor X to form factor Xa via the internal and external coagulation pathways plays a central role in the coagulation cascade. Factor Xa is a component of the emerging prothrombinase complex, the action of which leads to the conversion of prothrombin to thrombin. As a result, these reactions lead to the formation of a fibrin clot and platelet activation by thrombin. One molecule of factor 2 Xa catalyzes the formation of more than 1,000 thrombin molecules, which is called the “thrombin explosion”. The reaction rate of prothrombinase-bound factor Xa increases by 300,000 times compared to that of free factor Xa, which provides a sharp jump in the level of thrombin. Selective factor Xa inhibitors can stop the “thrombin burst”. Thus, rivaroxaban has an impact on the results of some specific or general laboratory tests used to evaluate clotting systems. Pharmacodynamic effects In humans, dose-dependent inhibition of factor Xa activity is observed. Rivaroxaban has a dose-dependent effect on prothrombin time and is closely correlated with plasma concentrations (r=0.98) if the Neoplastin kit is used for analysis. If you use other reagents, the results will be different. Prothrombin time should be measured in seconds, since the INR (International Normalized Ratio) is calibrated and certified only for coumarin derivatives and cannot be used for other anticoagulants. In patients undergoing major orthopedic surgery, the 5/95 percentiles for prothrombin time (Neoplastin) 2-4 hours after taking the pill (i. e. at the maximum effect) vary from 13 to 25 seconds. In patients receiving rivaroxaban for the treatment and prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE), the 5/95 percentiles for prothrombin time (Neoplastin) 2-4 hours after taking the pill (i. e. at maximum effect) range from 17 to 32 seconds in patients taking 15 mg twice daily, and from 15 to 30 seconds in patients taking 20 mg once daily. Rivaroxaban also dose-dependently increases activated partial thromboplastin time (aPTT) and HepTest score; however, these parameters are not recommended for evaluating the pharmacodynamic effects of rivaroxaban. Monitoring of blood clotting parameters is not required during treatment with rivaroxaban. However, if there is a clinical justification for this (for example, in case of drug overdose or in case of emergency surgery), the concentration of rivaroxaban can be measured using a calibrated quantitative test of anti-factor Xa (for example, STA-Liquid Anti-Xa, manufacturer Diagnostics Stago CAC, France or similar). In healthy men and women over 50 years of age, QT prolongation under the influence of rivaroxaban was not observed

Indications

• Prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgeries on the lower extremities.
• Prevention of recurrent deep vein thrombosis (DVT) or pulmonary embolism (PE) after at least 6 months of DVT or PE treatment.

Use during pregnancy and lactation

It is contraindicated in children under 18 years of age, pregnant women and during lactation.

Pregnancy

There are no data on the use of rivaroxaban in pregnant women.

Data obtained on experimental animals showed a pronounced toxicity of rivaroxaban to the maternal body, associated with the pharmacological action of the drug (for example, complications in the form of hemorrhages) and leading to reproductive toxicity.

Rivaroxaban is contraindicated during pregnancy due to the possible risk of bleeding and its ability to cross the placenta.

Women with preserved reproductive capacity should use effective methods of contraception during treatment with rivaroxaban.

Lactation

There are no data on the use of rivaroxaban for the treatment of women during lactation.

Data obtained on experimental animals show that rivaroxaban is excreted in breast milk. Rivaroxaban can only be used after discontinuation of breast-feeding.

Recommendations for use

Inside, regardless of food intake. If the patient is unable to swallow the tablet whole, the Xarelto ® tablet can be crushed and mixed with water or a liquid food, such as applesauce, immediately before ingestion. A crushed tablet of Xarelto® can be administered through a gastric tube. The position of the probe in the gastrointestinal tract should be additionally agreed with the doctor before taking Xarelto®. The crushed tablet should be administered through a gastric tube in a small amount of water, after which it is necessary to introduce a small amount of water in order to wash off the remnants of the drug from the walls of the probe. Prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgeries on the lower extremities. In order to prevent VTE during large orthopedic operations, it is recommended to prescribe 1 tablet of 10 mg 1 time a day. Duration of treatment: – 5 weeks after major hip surgery; – 2 weeks after major knee surgery. The initial dose should be taken 6-10 hours after surgery, provided that hemostasis is achieved. Actions if you miss taking the drug If you miss taking the drug, the patient should take a tablet of Xarelto® in a dosage of 10 mg immediately and continue treatment the next day,1 tablet per day, as before. Prevention of recurrent deep vein thrombosis (DVT) or pulmonary embolism (PE) after at least 6 months of treatment for DVT or PE After at least 6 months of treatment for deep vein thrombosis or pulmonary embolism, the recommended dose of Xarelto® is 10 mg once a day or 20 mg once a day, depending on the individual risk ratio of DVT or PE relapse and the risk of bleeding. Actions if you miss taking the drug, you should follow the prescribed regimen of taking the drug. If you miss taking the drug when prescribing Xarelto® at a dosage of 15 mg twice a day, you should immediately take the missed tablet to ensure that the total daily dose of the drug is 30 mg. In this case, it is allowed to take two tablets of Xarelto® in a dosage of 15 mg at one time. The next day, you should continue treatment in accordance with the recommended schedule of taking the drug. If you miss taking the drug when prescribing Xarelto® once a day, you should immediately take the missed tablet to ensure that the daily dose of the drug is taken. The next day, you should continue treatment in accordance with the recommended schedule of taking the drug. Individual patient groups Dose adjustments based on the patient’s age (over 65 years), gender, body weight, or ethnic group are not required. The safety and efficacy of the drug in children and adolescents under 18 years of age have not been established. Patients with impaired liver Functionrivaroxaban is contraindicated in patients with liver diseases accompanied by coagulopathy, which causes a clinically significant risk of bleeding (see the section “Contraindications”). Patients with other liver diseases do not need to change the dose (see the section “Pharmacological properties”).11 Limited clinical data obtained in patients with moderate hepatic insufficiency (Child-Pugh class B) indicate a significant increase in the pharmacological activity of the drug. In patients with severe hepatic insufficiency (Child-Pugh class C), there are no clinical data (see sections “Contraindications”, “Pharmacological properties”). Patients with impaired renal function The current limited clinical data show a significant increase in rivaroxaban concentrations in patients with severe renal impairment (CLcr 15-29 ml / min). For the treatment of this category of patients, Xarelto® should be used with caution. The use of rivaroxaban is not recommended in patients with CLcr less than 15 ml / min (see sections “Pharmacological properties”, “Contraindications”, “Special instructions”). • When Xarelto® is prescribed for the prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery on the lower extremities, with mild or moderate renal impairment (CLcr 50-80 ml/min or 30-49 ml/min, respectively), no dose adjustment is required (see section “Pharmacological properties”). • When Xarelto® is prescribed for the treatment and prevention of recurrent deep vein thrombosis (DVT) or pulmonary embolism (PE) in patients with mild renal impairment (CLR 50-80 ml/min), no dose adjustment is required (see section “Pharmacological properties”). Patients with moderate (CLcr 30-49 ml/min) or severe (CLcr 15-29 ml/min) renal impairment should take Xarelto® at a dose of 15 mg twice daily for the first three weeks.Subsequently, when the recommended dose of Xarelto® is 20 mg once a day, you should consider reducing the dose to 15 mg once a day if the risk of bleeding is higher than the risk of recurrent DVT and PE. Recommendations for the use of Xarelto® at a dose of 15 mg are based on pharmacokinetic modeling and have not been studied in clinical studies (see sections “Special instructions”, “Pharmacological properties”). When using Xarelto® in a dosage of 10 mg, no dose adjustment is required. Note: Information on the use of Xarelto® at a dose of 10 mg 1 time per day in patients with atrial fibrillation of non-valvular origin, who have undergone percutaneous coronary intervention (PCI) with stent placement and who have an average degree of impaired po function-12 checks (CLcr 30-49 ml / min), is available in the instructions for medical use of Xarelto® 15/20 mg (registration number LP-001457). Transfer of patients from treatment with vitamin K antagonists (VKA) to Xarelto® When transferring a patient from AVC to Xarelto®, the INR value will falsely increase after taking Xarelto®. Therefore, INR cannot be used to monitor the anticoagulant effect of Xarelto®(see “Interaction with other medicinal products”). In the prevention of stroke and systemic thromboembolism, AVC treatment should be discontinued and Xarelto® treatment should be initiated if the INR is less than 3.0. In DVT and PE, AVC treatment should be discontinued and Xarelto® treatment should be initiated if the INR is less than 2.5. Patients should be switched from Xarelto® to vitamin K antagonist (VKA)therapy There is a possibility of insufficient anticoagulant effect when transferring patients from Xarelto® to AVC. During the transition period associated with switching to another anticoagulant drug, it is necessary to ensure a continuous and sufficient anticoagulant effect. It should be borne in mind that Xarelto® may contribute to an increase in INR. When transferring a patient from Xarelto® to AVC, both drugs should be administered simultaneously until the INR reaches ≥2.0. During the first two days of the transition period, the standard dose of AVA should be used, and then the INR value should be used. During the period of co-use of Xarelto® and AVK, INR should be determined no earlier than 24 hours (after the previous dose, but before taking the next dose of Xarelto®). After discontinuation of Xarelto®, INR determination with a sufficient degree of reliability is possible 24 hours after taking the last dose of the drug (see “Interaction with other drugs”). Transfer of patients from parenteral anticoagulants to Xarelto®When transferring a patient from parenteral anticoagulants to Xarelto®, Xarelto® should be started 0-2 hours before the expected next dose of a parenteral drug (for example, low-molecular-weight heparin) or during the withdrawal of a long-term parenteral drug (for example, intravenous unfractionated heparin). Switching patients from Xarelto® to parenteral anticoagulants, stop taking Xarelto® and administer the first dose of parenteral anticoagulant during the expected next dose of Xarelto®.

Contraindications

• Hypersensitivity to rivaroxaban or any excipients contained in the tablet.
• Clinically significant active bleeding (for example, intracranial bleeding, gastrointestinal bleeding).
• An injury or pathological condition associated with an increased risk of major bleeding (for example, an existing or recent gastrointestinal ulcer, the presence of malignancies with a high risk of bleeding, recent brain or spinal cord injuries, recent surgical procedures on the brain, spinal cord or eyes, recent intracranial hemorrhage, diagnosed or suspected esophageal varicose veins, arteriovenous malformations, vascular aneurysms or large vascular abnormalities of the brain or spinal cord).
• Concomitant therapy with any other anticoagulants, for example, unfractionated heparin (UFH), low-molecular-weight heparins (enoxaparin, dalteparin, etc. ), heparin derivatives (fondaparinux, etc. ), oral anticoagulants (warfarin, apixaban, dabigatran, etc. ), except when the patient is transferred from therapy or to therapy with Xarelto®, or when UFH is prescribed in low doses to maintain patency of the central venous or arterial catheter.
• Liver diseases associated with coagulopathy that causes a clinically significant risk of bleeding, including patients with Child-Pugh Class B and C cirrhosis.
• Pregnancy and breast-feeding period.
• Children and adolescents under 18 years of age (efficacy and safety in patients of this age group have not been established).
• Severe renal impairment (CLcr
• Hereditary lactose or galactose intolerance (for example, congenital lactase deficiency or glucose-galactose malabsorption), because the drug contains lactose.

WITH CAUTION The drug should be used with caution: 

• In the treatment of patients with an increased risk of bleeding (including those with a congenital or acquired tendency to bleed, uncontrolled severe arterial hypertension, acute gastric and duodenal ulcer, recent gastric and duodenal ulcer, vascular retinopathy, recent intracranial or intracerebral hemorrhage, spinal or brain vascular pathology, after recent surgery on the brain, spinal cord or eyes, with a history of bronchiectasis or pulmonary hemorrhage).
• In the treatment of patients with moderate renal impairment (CLcr 30-49 ml / min), receiving concomitant medications that increase the concentration of rivaroxaban in blood plasma (see the section “Interaction with other drugs”).
• In the treatment of patients with severe renal impairment (CLcr 15-29 ml / min) (see section “Special instructions”).
• Rivaroxaban is not recommended for use in patients receiving systemic treatment with azole antifungal drugs (for example, ketoconazole) or HIV protease inhibitors (for example, ritonavir) (see sections “Interaction with other drugs”, “Special instructions”).
• Patients with severe renal impairment (CLcr 15-29 ml / min), an increased risk of bleeding, and patients receiving concomitant systemic treatment with azole antifungal drugs or HIV protease inhibitors should be closely monitored after starting treatment for timely detection of bleeding complications. Such monitoring may include regular physical examination of patients, careful monitoring of the discharge by drainage of the surgical wound, and periodic measurements of hemoglobin levels. Any decrease in hemoglobin or blood pressure, for which there is no explanation, is a reason to search for the source of bleeding.
• In patients receiving concomitant medications that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelet agents, other antithrombotics, or selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SSRIs).
• In patients at risk of exacerbation of gastric and duodenal ulcers, the appointment of preventive anti-ulcer treatment may be justified.

Side effects

The safety of Xarelto® was evaluated in four phase III studies involving 6,097 patients undergoing major orthopedic surgery on the lower extremities (total knee or hip replacement) and 3,997 patients hospitalized for medical reasons treated with Xarelto® 10 mg for up to 39 days, as well as in three phase III studies of venous thromboembolism, including 4,566 patients treated with Xarelto® or 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 with a treatment duration of up to 21 months.

In addition, two phase III trials involving 7,750 patients reported safety data in patients with nonvalvular atrial fibrillation who received at least one dose of Xarelto® for up to 41 months, as well as 10,225 patients with ACS who received at least one dose of 2.5 mg (2 times/day). or 5 mg (2 times / day) Xarelto® in addition to acetylsalicylic acid or acetylsalicylic acid therapy with clopidogrel or ticlopidine, the duration of treatment is up to 31 months.

Given the mechanism of action, the use of Xarelto® may be associated with an increased risk of latent or obvious 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 co-administered 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 be manifested by 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, symptoms of myocardial ischemia, such as chest pain and angina pectoris, have developed due to anemia.

Known complications secondary to severe bleeding, such as interfascial space syndrome and renal failure, have been reported with Xarelto®. Therefore, the possibility of bleeding should be considered when evaluating a patient receiving anticoagulants.

Summary data on the frequency of adverse reactions reported for Xarelto® are given below. In groups divided by frequency, undesirable effects are presented in order of decreasing severity, as follows: very common (≥1/10); common (≥1/100 and <1/10); uncommon (≥1/1000 and <1/100); rare (≥1/10,000 and

All adverse reactions that occurred during treatment in patients participating in phase III clinical trials

From the hematopoietic system: often-anemia (including relevant laboratory parameters); infrequently-thrombocythemia (including elevated platelet count)*.

From the cardiovascular system: often-a marked decrease in blood pressure, hematoma; infrequently-tachycardia.

From the side of the visual organ: often – hemorrhage in the eye (including conjunctival hemorrhage).

From the digestive system: often – bleeding gums, gastrointestinal bleeding (including rectal bleeding), gastrointestinal pain, dyspepsia, nausea, constipation*, diarrhea, vomiting*; infrequently-dry mouth.

From the liver: infrequently-impaired liver function; rarely-jaundice.

From the side of laboratory parameters: often-increased activity of hepatic transaminases; infrequently-increased bilirubin concentration, increased ALP activity*, increased LDH activity*, increased lipase activity*, increased amylase activity*, increased GGT activity*; rarely-increased concentration of conjugated bilirubin (with or without concomitant increase in ALT activity).

Nervous system disorders: often – dizziness, headache; infrequently-intracerebral and intracranial hemorrhage, short-term fainting.

From the genitourinary system: frequently – urogenital bleeding (including hematuria and menorrhagia**), renal failure (including increased creatinine concentration, increased urea concentration)*.

Respiratory system disorders: often-nosebleeds, hemoptysis.

Skin and subcutaneous tissue disorders: often-pruritus (including infrequent cases of generalized pruritus), rash, ecchymoses, skin and subcutaneous hemorrhages; infrequently-urticaria.

From the immune system: infrequently – allergic reactions, allergic dermatitis.

Musculoskeletal disorders: often-pain in the extremities*; infrequently-hemarthrosis; rarely-muscle hemorrhage.

From the body as a whole: often – fever*, peripheral edema, deterioration of overall muscle strength and tone (including weakness, asthenia); infrequently-deterioration of general well – being (including malaise); rarely-local edema*.

Other services: often – hemorrhage after the procedures performed (including postoperative anemia and bleeding from the wound), excessive hematoma in the bruise; infrequently-discharge from the wound*; rarely-vascular pseudoaneurysm***.

* – registered after major orthopedic surgeries.

* * – VTE treatment was recorded as very frequent in women

* * * – were recorded as infrequent in the prevention of sudden death and myocardial infarction in patients after acute coronary syndrome (after percutaneous interventions).

During post-marketing monitoring, cases of the following adverse reactions were reported, the development of which was temporarily associated with the use of Xarelto®. It is not possible to estimate the frequency of occurrence of such adverse reactions in the framework of post-marketing monitoring.

From the immune system: angioedema, allergic edema. In a phase III RCT, such undesirable effects were considered infrequent (from >1/1000 to >

From the liver: cholestasis, hepatitis (including hepatocellular damage). In a phase III RCT, such undesirable effects were considered rare (from >1/10,000 to >

From the hematopoietic system: thrombocytopenia. In a phase III RCT, such undesirable effects were considered infrequent (from >1/1000 to >

Musculoskeletal disorders: frequency unknown – increased subfascial pressure syndrome (compartment syndrome) due to muscle hemorrhage.

From the urinary system: frequency unknown – renal failure/acute renal failure due to bleeding leading to renal hypoperfusion.

Interaction

Pharmacokinetic interaction

The elimination of rivaroxaban is mainly carried out by liver metabolism mediated by the cytochrome P450 system (CYP3A4, CYP2J2), as well as by renal excretion of unchanged drug substance using the P – gp/Bcrp (P-glycoprotein/breast cancer resistance protein) transporter systems.

Rivaroxaban does not inhibit or induce the CYP3A4 isoenzyme and other important cytochrome isoforms.

Concomitant use of rivaroxaban and strong inhibitors of the CYP3A4 isoenzyme and P-glycoprotein may lead to a decrease in renal and hepatic clearance and, thus, significantly increase systemic exposure.

The combined use of rivaroxaban and an antifungal agent from the azole group ketoconazole (400 mg 1 time / day), which is a strong inhibitor of CYP3A4 and P-glycoprotein, led to an increase in the average steady-state AUC of rivaroxaban by 2.6 times and an increase in the average Cmax of rivaroxaban by 1.7 times, which was accompanied by a significant increase in the pharmacodynamic effect of the drug.

The combined use of rivaroxaban and the HIV protease inhibitor ritonavir (600 mg 2 times / day), which is a strong inhibitor of CYP3A4 and P-glycoprotein, led to an increase in the average steady-state AUC of rivaroxaban by 2.5 times and an increase in the average Cmax of rivaroxaban by 1.6 times, which was accompanied by a significant increase in the pharmacodynamic effect of the drug. Therefore, rivaroxaban is not recommended for use in patients receiving systemic treatment with azole antifungal drugs or HIV protease inhibitors.

It is expected that other drugs that strongly inhibit only one of the routes of elimination of rivaroxaban-with the participation of CYP3A4 CYP3A4 or P-glycoprotein-will increase the concentration of rivaroxaban in plasma to less significant values.

Clarithromycin (500 mg twice daily), a strong inhibitor of the CYP3A4 isoenzyme and a moderate inhibitor of P-glycoprotein, caused an increase in the AUC values by 1.5 times and Cmax of rivaroxaban by 1.4 times. This increase is on the order of normal variability in AUC and Cmax and is considered clinically insignificant.

Erythromycin (500 mg 3 times / day), a moderate inhibitor of the CYP3A4 isoenzyme and P-glycoprotein, caused a 1.3-fold increase in the AUC and Cmax values of rivaroxaban. This increase is on the order of normal variability in AUC and Cmax and is considered clinically insignificant.

In patients with renal insufficiency (creatinine clearance < 80-50 ml/min), erythromycin (500 mg 3 times / day) caused an increase in rivaroxaban AUC values by 1.8 times and Cmax by 1.6 times compared to patients with normal renal function who did not receive concomitant therapy. In patients with renal insufficiency (creatinine clearance 50-30 ml/min), erythromycin caused a 2.0-fold increase in rivaroxaban AUC and 1.6-fold increase in Cmax compared to patients with normal renal function who did not receive concomitant therapy.

Fluconazole (400 mg once daily), a moderate inhibitor of the CYP3A4 isoenzyme, caused an increase in the average AUC of rivaroxaban by 1.4 times and an increase in the average Cmax by 1.3 times. This increase is on the order of normal variability in AUC and Cmax and is considered clinically insignificant.

Concomitant use of rivaroxaban with dronedarone should be avoided due to limited clinical data on co-administration.

The combined use of rivaroxaban and rifampicin, which is a strong inducer of CYP3A4 and P-glycoprotein, resulted in a decrease in the average AUC of rivaroxaban by approximately 50% and a parallel decrease in its pharmacodynamic effects. Concomitant administration of rivaroxaban with other potent CYP3A4 inducers (e. g., phenytoin, carbamazepine, phenobarbital, or St. John’s wort) may also result in a decrease in rivaroxaban plasma concentrations. A decrease in rivaroxaban plasma concentrations was found to be clinically insignificant.

Pharmacodynamic interaction

After simultaneous administration of enoxaparin sodium (a single dose of 40 mg) and rivaroxaban (a single dose of 10 mg), a cumulative effect on the activity of anti-factor Xa was observed, which was not accompanied by additional cumulative effects on blood clotting tests (prothrombin time, APTT). Enoxaparin did not alter the pharmacokinetics of rivaroxaban.

No clinically significant prolongation of bleeding time was observed after concomitant administration of rivaroxaban 15 mg and naproxen 500 mg. However, individuals may have a more pronounced pharmacodynamic response.

There was no pharmacokinetic interaction between rivaroxaban at a dose of 15 mg and clopidogrel (a shock dose of 300 mg followed by a maintenance dose of 75 mg), but a significant increase in bleeding time was found in some patients, which did not correlate with the degree of platelet aggregation and the content of P-selectin or GPIIb/IIIa receptor.

Switching patients from warfarin (MHO from 2 to 3) to rivaroxaban (20 mg) or from rivaroxaban (20 mg) to warfarin (MHO from 2 to 3) was accompanied by a more than additive increase in prothrombin time/INR (Neoplastin) (in some cases up to 12), while the effects of changes in APTT, suppression of factor Xa activity, and endogenous thrombin potential (EPT) were additive.

To assess the pharmacodynamic effects of Xarelto® during the transition period, an analysis of anti-Xa factor, PiCT and HepTest® can be performed, if the indicators determined during them were not affected by warfarin.

Starting from the 4th day after warfarin withdrawal, all tests (including PV, APTT, suppression of factor Xa activity and EPT (endogenous thrombin potential))were performed. only the effect of Xarelto®was reflected.

To assess the pharmacodynamic effects of warfarin during the transition period, you can use the MHO indicator measured at the moment when Cmax of rivaroxaban is reached (24 hours after taking a dose of rivaroxaban), since at this point in time the effect of rivaroxaban on the test results is minimal.

There was no pharmacokinetic interaction between warfarin and rivaroxaban.

The drug interaction of Xarelto® with AVC phenindione has not been studied. It is recommended to avoid transferring patients from Xarelto®therapy as much as possible for AVK therapy with phenindione and vice versa.

There is limited experience in transferring patients from AVC therapy with acenocoumarol to Xarelto®.

If there is a need to transfer the patient from therapy with Xarelto® If the drug is used in combination with phenindione or acenocoumarol, then special care should be taken, and daily monitoring of the pharmacodynamic effect of drugs (MHO, prothrombin time) should be carried out immediately before taking the next dose of Xarelto®. If there is a need to transfer a patient from AVC therapy with phenindione or acenocoumarol to Xarelto® therapy, special care should be taken, monitoring of the pharmacodynamic effect of drugs is not required.

Concomitant use with other medications

No clinically significant pharmacokinetic or pharmacodynamic interactions were observed when rivaroxaban was co-administered with midazolam (a CYP3A4 substrate), digoxin (a P-glycoprotein substrate), or atorvastatin (a CYP3A4 and P-glycoprotein substrate).

There was no clinically significant interaction with food.

Incompatibility

Unknown.

Influence on laboratory parameters

The effect on blood clotting parameters (PV, APTT, HepTest®) corresponds to what is expected, taking into account the mechanism of action of Xarelto®.

How to take, course of use and dosage

For the prevention of VTE in large orthopedic operations

It is intended for oral use of 10 mg 1 time/day. The duration of treatment is determined by the type of orthopedic intervention.

Duration of treatment: 5 weeks after major hip surgery; 2 weeks after major knee surgery.

Rivaroxaban can be taken regardless of food intake.

The initial dose should be taken 6-10 hours after surgery, provided that hemostasis is achieved.

If a dose is missed, the patient should take rivaroxaban immediately and continue treatment the next day with 1 tablet / day, as before.

Switching patients from vitamin K antagonists (VKA) to Xarelto

If MHO < 3, AVC treatment should be discontinued and Xarelto treatment should be initiated. When transferring patients from AVC to Xarelto, MHO values will falsely increase after taking Xarelto. Therefore, the MHO score cannot be used to monitor the anticoagulant effect of Xarelto.

Switching from Xarelto to Vitamin K Antagonists (VKA)

There is a possibility of insufficient anticoagulant effect when transferring patients from Xarelto to AVC. During the transition period associated with switching to another anticoagulant drug, it is necessary to ensure a continuous and sufficient anticoagulant effect. It should be borne in mind that Xarelto may contribute to an increase in the MHO index.

When transferring a patient from Xarelto to AVC, both drugs should be given simultaneously until the MHO reaches a value of ≥ 2. During the first two days of the transition period, the standard dose of AVA should be used, and then the MHO value should be used. During the period of co-use of Xarelto and AVK, MHO should be determined no earlier than 24 hours (after the previous dose, but before taking the next dose of Xarelto). After discontinuation of Xarelto, MHO determination with a sufficient degree of reliability is possible 24 hours after the last dose of the drug.

Switching from parenteral anticoagulants to Xarelto

When transferring a patient from parenteral anticoagulants to Xarelto, Xarelto should be started 0-2 hours before the expected next dose of a parenteral drug (for example, low-molecular-weight heparin) or during the withdrawal of a long-term parenteral drug (for example, intravenous use of unfractionated heparin).

Switching from Xarelto to parenteral anticoagulants

You should stop taking Xarelto and enter the first dose of parenteral anticoagulant at the time when you should have taken the next dose of Xarelto.

Use in selected patient groups

No dose adjustment is required depending on the patient’s age (over 65 years), gender, body weight, or ethnicity.

In case of liver disease

Rivaroxaban is contraindicated in patients with liver diseases associated with coagulopathy, which causes a clinically significant risk of bleeding. Patients with other liver diseases do not need to change the dose. The available limited clinical data obtained in patients with moderate hepatic insufficiency (Child-Pugh class B) indicate a significant increase in the pharmacological activity of the drug. There are no clinical data available for patients with severe hepatic insufficiency (Child-Pugh class C).

When prescribing rivaroxaban to patients with mild (creatinine clearance 80-50 ml/min) or moderate (creatinine clearance

With kidney disease

Available limited clinical data obtained in patients with severe renal insufficiency (CC For the treatment of this category of patients, rivaroxaban should be used with caution.

Rivaroxaban is not recommended in patients with creatinine clearance < 15 ml/min.

Overdose

Rare cases of overdose up to 600 mg without complications of bleeding or other adverse reactions have been reported. Due to limited absorption, a saturation effect is expected without further increasing the average rivaroxaban plasma content at hypertherapeutic doses of 50 mg or higher.

The specific antidote of rivaroxaban is unknown. In case of overdose, activated charcoal 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.

Treatment of bleeding

If a bleeding complication occurs, the next dose of the drug should be postponed or the treatment should be discontinued, depending on the situation. The elimination half-life of rivaroxaban is approximately 5-13 hours. Treatment should be selected individually, according to the severity and location of the bleeding.

If necessary, appropriate symptomatic treatment can be used, such as mechanical compression (for example, in the case of severe nosebleeds), surgical hemostasis with bleeding control procedures, fluid replenishment and hemodynamic support, the use of blood preparations (red blood cell mass or fresh frozen plasma, depending on concomitant anemia or coagulopathy) or platelets.

If the measures listed above do not eliminate bleeding, a specific procoagulant may be prescribed, such as prothrombin complex concentrate, activated prothrombin complex concentrate, or recombinant factor VIIa (rf VIIa). However, to date, the experience of using these drugs in the treatment of patients receiving rivaroxaban is very limited.

Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban. There is limited experience with tranexamic acid and no experience with aminocaproic acid and aprotinin in patients receiving 20 Xarelto®. There is no scientific justification for the feasibility or experience of using the systemic hemostatic drug desmopressin in patients receiving Xarelto®.

Description

Round biconvex tablets of pink color covered with a film shell; the method of extrusion is engraved: on one side – a triangle with the dosage designation (10), on the other – a branded Bayer cross. Type of tablets in a kink: a homogeneous mass of white color, surrounded by a pink shell.

Special instructions

Antithrombotic drugs, including rivaroxaban, should be used with caution in the treatment of patients with an increased risk of bleeding.

In patients with severe renal insufficiency (CC Because of the underlying disease, these patients are at increased risk of both bleeding and thrombosis.

The use of rivaroxaban has not been studied in clinical trials in surgical interventions for hip fractures.

If there is an unexplained decrease in hemoglobin or blood pressure, it is necessary to look for the source of bleeding.

No prolongation of the QT interval was observed during treatment with rivaroxaban.

When performing spinal puncture and epidural / spinal anesthesia for patients receiving platelet aggregation inhibitors to prevent thromboembolic complications, there is a risk of developing an epidural or spinal hematoma, which can lead to prolonged paralysis. The risk of these events is further increased with the use of permanent catheters or concomitant use of medications that affect hemostasis.

An injury during an epidural or spinal tap or repeated puncture may also contribute to an increased risk. Patients should be monitored for signs or symptoms of neurological disorders (such as numbness or weakness in the legs, bowel or bladder dysfunction).

If neurological disorders are detected, urgent diagnosis and treatment is necessary. The physician should weigh the potential benefits and risks before performing spinal surgery in patients receiving anticoagulants or preparing to receive anticoagulants to prevent thrombosis. The epidural catheter is removed no earlier than 18 hours after the last dose of rivaroxaban is administered. Rivaroxaban should not be administered earlier than 6 hours after removal of the epidural catheter. In case of a traumatic puncture, the appointment of rivaroxaban should be postponed for 24 hours.

If an invasive procedure or surgical intervention is necessary, Xarelto should be discontinued at least 24 hours before the intervention and based on the doctor’s opinion.

If the procedure cannot be postponed, the increased risk of bleeding should be evaluated against the need for urgent intervention.

Xarelto should be resumed after an invasive procedure or surgical intervention, provided that appropriate clinical parameters and adequate hemostasis are present.

Use in patients with liver function disorders

Rivaroxaban is contraindicated in patients with liver diseases associated with coagulopathy, which causes a clinically significant risk of bleeding. Patients with other liver diseases do not need to change the dose.

The available limited clinical data obtained in patients with moderate hepatic insufficiency (Child-Pugh class B) indicate a significant increase in the pharmacological activity of the drug. There are no clinical data available for patients with severe hepatic insufficiency (Child-Pugh class C).

Use in patients with impaired renal function

When prescribing rivaroxaban to patients with mild (creatinine clearance 80-50 ml / min) or moderate (creatinine clearance

Available limited clinical data obtained in patients with severe renal insufficiency (CC For the treatment of this category of patients, rivaroxaban should be used with caution.

Rivaroxaban is not recommended in patients with creatinine clearance < 15 ml/min.

Safety data obtained from preclinical studies

With the exception of effects associated with increased pharmacological action (bleeding), when analyzing preclinical data obtained in pharmacological safety studies, no specific danger to humans was found.

Influence on the ability to drive vehicles and mechanisms

Studies of the effect of rivaroxaban on the ability to drive vehicles and work with potentially dangerous moving mechanisms have not been conducted.

Fainting and dizziness were infrequently reported in the postoperative period. Patients who experience these adverse reactions should not drive vehicles or work with moving machinery.

Form of production

Xarelto tablets.

Storage conditions

At a temperature not exceeding 30 °C. Keep out of reach of children.

Shelf

life 3 years Do not apply after the expiration date.

Active ingredient

Rivaroxaban

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Adults as prescribed by a doctor

Indications

Consequences of stroke, Thrombophlebitis, Prevention of heart attacks and strokes, Angina pectoris, Prevention of thrombosis