Rivaroxaban - instructions for use, ratings, analogs and release forms (tablets 2.5 mg, 10 mg, 15 mg and 20 mg) of a medicament for the treatment of thrombosis and embolism, prevention of stroke and heart attack in adults, children and in pregnancy. Composition

In this article, you can read the instructions for using the drug Rivaroxaban. There are reviews of visitors to the site - consumers of this medication, as well as opinions of specialists on the use of Rivaroxaban in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues Rivaroksabana in the presence of existing structural analogues.Use for treatment of thrombosis and embolism, prevention of stroke and heart attack in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

Rivaroxaban - selective direct inhibitor of factor 10a for oral administration. Activation of factor 10 with the formation of factor 10a through its own and external pathways plays a central role in the coagulation cascade.

Rivaroxaban has a dose-dependent effect on prothrombin time and is highly correlated with plasma concentration when analyzed with the Neoplastin kit (other results will differ if other reagents are used).

Also, rivaroxaban dose-dependently increases the APTT and the Heptest result, but these parameters are not recommended for evaluating the pharmacodynamic effects of rivaroxaban.

Composition

Rivaroxaban + auxiliary substances.

Pharmacokinetics

After oral administration rivaroxaban is rapidly absorbed, the absolute bioavailability is high and is 80-100%. The intake of food does not affect the AUC and Cmax of rivaroxaban. The pharmacokinetics of rivaroxaban are characterized by moderate variability; Individual variability (coefficient of variability) is 30-40%, except for the day and the next day after the operation, when the variability is high (70%).The binding with plasma proteins, mainly with albumin, is 92-95%. Rivaroxaban is excreted mainly in the form of metabolites (approximately 2/3 of the dose), half of them excreted by the kidneys, and the other half with the feces. 1/3 of the applied dose is directly excreted by the kidneys in the form of unchanged substance, it is believed, mainly through active renal secretion. The metabolism of rivaroxaban occurs with the participation of CYP3A4 and CYP2J2 isoenzymes, as well as enzymes independent of the cytochrome P450 system. The main participants in the biotransformation are a morpholino group undergoing oxidative decomposition, and amide groups undergoing hydrolysis.

Indications

For oral administration in a single dose of 2.5 mg in combination therapy with Acetylsalicylic acid or with acetylsalicylic acid and ticlopidine or clopidogrel:

• prevention of atherothrombosis in adult patients who underwent acute coronary syndrome with an increase in cardiac biomarkers.

For oral administration in a single dose of 10 mg:

• prevention of venous thromboembolism in adult patients who underwent operations on the knee and hip joints.

For oral administration in a single dose of 15-20 mg:

• prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, arterial hypertension, age 75 and over, diabetes mellitus, stroke and transient ischemic attack.

Forms of release

Tablets 2.5 mg, 10 mg, 15 mg and 20 mg.

Instructions for use and dosing regimen

Inside, with food.

If the patient is unable to swallow the whole tablet, it can be ground and mixed with water or liquid food, such as apple puree, just before taking. After taking a crushed tablet of 15 or 20 mg, you must immediately take food.

A crushed tablet can be administered via a gastric tube. The position of the probe in the digestive tract should be agreed with the doctor before admission. The ground tablet should be injected through a gastric tube in a small amount of water, after which a small amount of water must be introduced in order to wash off the drug residues from the probe walls.After taking a crushed tablet of 15 or 20 mg, the enteral feeding should be taken immediately.

Prevention of stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation

The recommended dose is 20 mg 1 time per day.

For patients with impaired renal function (creatinine clearance of 49-30 ml / min), the recommended dose is 15 mg 1 time per day.

The recommended maximum daily dose is 20 mg.

Duration of treatment

Therapy with rivaroxaban should be considered as a long-term treatment, until the benefits of treatment exceed the risk of possible complications.

Actions when skipping the dose

If the next dose is missed, the patient should immediately take the pill and continue the regular intake of the drug the next day in accordance with the recommended regimen. Do not double the dose taken to compensate for missed earlier.

Side effect

• the use of rivaroxaban may be accompanied by an increased risk of latent or obvious bleeding from any organ or tissue, which can lead to posthemorrhagic anemia;
• anemia, thrombocythemia;
• post-procedural hemorrhage (including postoperative anemia and bleeding from the wound);
• tachycardia;
• arterial hypotension (including hypotension during procedures);
• hemorrhage (including hematomas and rare cases of hemorrhage in the muscles);
• gastrointestinal hemorrhages (including hememesis, bleeding gums, bleeding from the rectum, hematuria, spotting from the genital tract, nosebleeds);
• nausea, vomiting;
• constipation, diarrhea;
• pain in the abdominal cavity;
• a feeling of discomfort in the stomach;
• dyspeptic phenomena;
• dry mouth;
• abnormal liver function;
• localized or peripheral edema;
• fatigue;
• weakness;
• asthenia;
• fever;
• urticaria (including cases of generalized urticaria);
• allergic dermatitis;
• dizziness;
• headache;
• syncopal states;
• pain in the limbs;
• itching (including cases of generalized itching);
• rashes on the skin;
• kidney failure (increase in blood levels of creatinine, urea);
• increased levels of lipase, amylase, blood bilirubin, level of alkaline phosphatase;
• increase in the level of conjugated bilirubin (with concomitant increase in hepatic transaminases or without it).

Contraindications

• clinically significant active bleeding (eg, intracranial, gastrointestinal);
• liver diseases accompanied by coagulopathy, which increases the risk of clinically significant bleeding;
• pregnancy;
• hypersensitivity to rivaroxaban.

Application in pregnancy and lactation

Contraindicated in the use of Rivaroxaban during pregnancy.

Use in children

Not noted.

special instructions

It is not recommended to use rivaroxaban in patients with severe renal insufficiency (CC less than 15 ml / min).

C rivaroxaban caution should be used when treating patients with renal insufficiency moderate severity (CC 30-49 ml / min) receiving concomitant therapy with drugs that are able to cause an increase rivaroxaban plasma concentrations, as well as in patients with CC less than 15-30 ml / min. In patients with severe renal insufficiency, the concentration of rivaroxaban in the blood plasma can be significantly increased, which can lead to an increased risk of bleeding.

Patients with severe renal insufficiency with an increased risk of bleeding and patients,who receive concomitant systemic therapy with antifungal azole agents or HIV protease inhibitors, should be closely monitored after the onset of treatment to detect hemorrhagic complications in a timely manner. Such control may include regular physical examination of the patient, careful observation of the surgical wound to be separated from the drainage, and periodic determination of the hemoglobin level.

Caution should be used rivaroxaban in the treatment of patients with an increased risk of bleeding, incl. if there are congenital or acquired diseases that lead to bleeding; uncontrolled severe hypertension; Gavage peptic ulcer in the phase of exacerbation; recently suffered peptic ulcer of the gastrointestinal tract; cardiovascular retinopathy; recent intracranial or intracerebral haemorrhage; intraspinal or intracerebral vascular pathology; the recently transferred neurosurgical (operation on the head, spinal cord) or ophthalmologic intervention.

Caution is needed when administering rivaroxaban to patients receiving medications that affect hemostasis, for example, NSAIDs,inhibitors of platelet aggregation or other antithrombotic agents.

Drug Interactions

With simultaneous application of rivaroxaban and strong inhibitors of the isoenzyme CYP3A4 and P-glycoprotein may lead to a decrease in renal and hepatic clearance and thus significantly increase the AUC of rivaroxaban.

The combined use of rivaroxaban and the azole Ketoconazole antifungal drug (400 mg once daily), which is a potent inhibitor of CYP3A4 and P-glycoprotein, resulted in a 2.6-fold increase in the mean equilibrium AUC of rivaroxaban and a 1.7-fold increase in mean Cmax of rivaroxaban, pharmacodynamic effects of the drug.

With the simultaneous use of rivaroxaban and the HIV protease inhibitor ritonavir (600 mg twice daily), which is a potent inhibitor of CYP3A4 and P-glycoprotein, resulted in a 2.5-fold increase in the mean equilibrium AUC of rivaroxaban and a 1.6-fold increase in mean Cmax of rivaroxaban, increased pharmacodynamic effects of the drug. In this regard, it is necessary to use with caution rivaroxaban in the treatment of patients simultaneously receiving systemic azole antifungal drugs or HIV protease inhibitors.

Clarithromycin (500 mg twice daily), a potent inhibitor of CYP3A4 and medium intensity inhibitor of the P-glycoprotein, caused a 1.5-fold increase in the mean AUC and a 1.4-fold increase in Cmax of rivaroxaban. This increase in AUC and an increase in Cmax varies within the norm and is considered clinically insignificant.

Erythromycin (500 mg 3 times a day), moderately inhibiting the isoenzyme CYP3A4 and P-glycoprotein, caused a 1.3-fold increase in the mean equilibrium values ​​of AUC and Cmax of rivaroxaban. This increase in AUC and an increase in Cmax varies within the norm and is considered clinically significant.

The simultaneous administration of rivaroxaban and rifampicin, which is a potent inducer of CYP3A4 and P-glycoprotein, resulted in approximately a 50% decrease in the mean AUC of rivaroxaban and a parallel decrease in its pharmacodynamic effects. The combined use of rivaroxaban with other potent inducers of CYP3A4 (eg, phenytoin, carbamazepine, Phenobarbital or St. John's wort) can also lead to a decrease in rivaroxaban concentrations in the blood plasma. Reducing the concentration of rivaroxaban in blood plasma is clinically insignificant.

After the combined use of enoxaparin (in a single dose of 40 mg) and rivaroxaban (in a single dose of 10 mg), an additive effect was observed with respect to the activity of the antifactor 10a, which is not accompanied by additional effects on the coagulation parameters (prothrombin time, APTT). Enoxaparin did not alter the pharmacokinetics of rivaroxaban.

There was no pharmacokinetic interaction between rivaroxaban and Clopidogrel (300 mg shock dose with the subsequent administration of a maintenance dose of 75 mg), but a subgroup of patients showed a clinically significant increase in bleeding time that did not correlate with platelet aggregation and P-selectin or GP2b / 3a receptor .

After the simultaneous administration of rivaroxaban and 500 mg of naproxen, no clinically relevant prolongation of bleeding time was observed. However, in individuals, a more pronounced pharmacodynamic response is possible.

Analogues of the drug Rivaroxaban

Structural analogs for the active substance:

• Xarelto.

Analogues on the curative effect (agents for the treatment of thrombosis and embolism):

• Aveliesin Brown;
• Agrenoks;
• Actylase;
• Angiovitis;
• Aspizol;
• Aspirin Cardio;
• Acenocoumarol;
• Acetylsalicylic acid;
• Brilint;
• Bufferin;
• Warfarin;
• Heparin;
• Detromb;
• Dipyridamole;
• Zilt;
• Calciparin;
• Cardiomagnet;
• Carinate;
• Karinat Forte;
• Clexan;
• Cleaver;
• Clopidex;
• Clopidogrel Plus;
• Collorite;
• Complymine;
• Coplawix;
• Xantinol nicotinate;
• Xarelto;
• Courantil;
• Lapal;
• Listab 75;
• Myristin;
• Parsedil;
• Pelentan;
• Pentoxifylline;
• Plavix;
• Plagril A;
• Plolidol 100;
• Ralofect;
• Reogluman;
• Reopoliglyukin;
• Ribasan forte;
• Cincumar;
• Streptase;
• Tagren;
• Telsartan;
• Tyclid;
• Ticlo;
• Trombo ACC;
• Thrombotomy;
• Thrombopol;
• Troparin;
• Ukidan;
• Phenylin;
• Phlogenzyme;
• Cibor;
• Egitromb.

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