Xarelto, 2.5mg 56 pcs.

Active ingredient

Composition

How to take, the dosage

After ACS, the recommended regimen for the prevention of vascular events is 1 tablet of Xarelto® 2.5 mg twice daily. Patients should also take a daily dose of acetylsalicylic acid 75-100 mg or a daily dose of acetylsalicylic acid 75-100 mg in combination with a daily dose of clopidogrel 75 mg or a standard daily dose of ticlopidine. The ongoing treatment should be regularly evaluated in terms of the balance between the risk of coronary events and the risk of bleeding. The duration of treatment is 12 months. Treatment may be prolonged up to 24 months for individual patients, since data on treatment of such duration are limited.

The treatment with Xarelto® 2.5 mg should be initiated as soon as possible after the patient is stabilized during the current ACS (including revascularization procedures). Treatment with Xarelto® should be initiated at least 24 hours after hospitalization. Xarelto® 2.5 mg should be started when parenteral anticoagulant therapy is usually discontinued.
Prevention of stroke, myocardial infarction and death due to cardiovascular causes, as well as prevention of acute limb ischemia and overall mortality in patients with CHD or VTE

Preventive regimen The recommended dosing regimen for prevention of vascular events in patients with CHD or IPA is 1 tablet of Xarelto® 2.5 mg twice daily in combination with a daily dose of acetylsalicylic acid 75-100 mg. Treatment with Xarelto® 2.5 mg should be long-term, provided that the benefits obtained outweigh the risks.

In patients with an acute thrombotic event or vascular intervention requiring dual antiplatelet therapy, the need for continued Xarelto® 2.5 mg twice daily should be evaluated depending on the type of thrombotic event or procedure and the type of antiplatelet therapy. Safety and efficacy of Xarelto® 2.5 mg when taken twice daily in combination with acetylsalicylic acid and clopidogrel or ticlopidine have been studied only in patients with recent ACS. The use of dual antiplatelet therapy in combination with Xarelto® 2.5 mg twice daily in patients with CHD or OSA has not been studied.

In patients diagnosed with CHD or ZPA, treatment with Xarelto® 2.5 mg twice daily in combination with acetylsalicylic acid 75100 mg once daily may be initiated at any time. If a dose is missed, the patient should continue Xarelto® 2.5 mg at the usual dose, which is the next scheduled appointment as recommended.

If the patient is unable to swallow the tablet whole, the Xarelto® tablet may be crushed or mixed with water or a liquid food such as apple puree immediately before ingestion. The crushed tablet of Xarelto® may be inserted through a gastric tube. The position of the tube in the gastrointestinal tract should be additionally coordinated with the physician before taking Xarelto®. The crushed tablet should be inserted through the gastric tube in a small amount of water, after which a small amount of water should be introduced to wash off the drug residues from the walls of the tube (see section “Pharmacological properties”).

Additional information for special patient groups

Patients with impaired liver function

Xarelto® is contraindicated in patients with liver disease with coagulopathy leading to a clinically significant risk of bleeding (see “Contraindications. “Contraindications”).

Patients with other liver diseases do not require dose adjustment (see section “Pharmacological properties”).

Limited clinical data obtained in patients with moderate hepatic impairment (Child-Pugh class B) indicate a significant increase in pharmacological activity. No clinical data are available for patients with severe hepatic impairment (Child-Pugh class C) (see sections “Contraindications”, “Pharmacological properties”).
Patients with impaired renal function

Dose adjustment is not required if Xarelto® is used in patients with impaired renal function of mild (CLKR 50-80 ml/min) or moderate (CLKR 30-49 ml/min) severity (see “Pharmacological properties” section).

Limited clinical data obtained in patients with severe renal impairment (CLKR 15-29 mL/min) indicate that plasma concentrations of rivaroxaban are significantly elevated in this patient population. Therefore, Xarelto® should be used with caution in these patients (see section “Special Indications”, “Pharmacological properties”).

The use of Xarelto® is not recommended in patients with CLR<15 ml/min (see section “Contraindications”).
Conversion from vitamin K antagonists (VKAs) to Xarelto®

If patients switch from VKAs to Xarelto® , the INR will be erroneously high after taking Xarelto®. The INR is not suitable for determining the anticoagulant activity of Xarelto® and therefore should not be used for this purpose (see section “Interaction with other drugs”).

Transition from Xarelto® therapy to therapy with vitamin K antagonists (VKAs)

There is a possibility of insufficient anticoagulant effect when switching from Xarelto® therapy to AVC therapy. In this regard, it is necessary to ensure continuous sufficient anticoagulant effect during such transition with the help of alternative anticoagulants. It should be noted that when switching from Xarelto® to AVC therapy, Xarelto® may contribute to increased INR.

In patients who switch from Xarelto® therapy to AVC therapy, the latter should be taken continuously until the INR value is >2.0. During the first two days of the transition period, standard doses of AVC should be used, subsequently adjusting the dose of AVC according to the INR value. Since patients receive both Xarelto® and AVC at the same time during this period, the INR should be assessed no earlier than 24 hours (after the first dose but before the next dose of Xarelto®). Thus, after discontinuation of Xarelto®, INR can be used as a reliable assessment of the therapeutic effect of AVC no earlier than 24 hours after the last dose of Xarelto® (see section “Interaction with other medicinal products”, “How to use and doses”).

Transition from therapy with parenteral anticoagulants to therapy with Xarelto®

. For patients receiving parenteral anticoagulants, Xarelto® therapy should be started 0 to 2 hours before the time of the next scheduled parenteral administration of the drug (e.g., low molecular weight heparin) or at the time of discontinuation of continuous parenteral administration of the drug (e.g., intravenous infractional heparin).

Transition from therapy with Xarelto® to therapy with parenteral anticoagulants

The first dose of Xarelto® should be stopped and the first dose of parenteral anticoagulant administered at the time the next dose of Xarelto® should have been taken.

Children and adolescents (birth to 18 years)

The safety and effectiveness of use in children and adolescents under 18 years has not been established.

Elderly patients

There is no need to adjust the dose according to age (see section “Pharmacological properties”).

Gender

Dose adjustment depending on gender is not required (see section “Pharmacological properties”).

Body weight

Dose adjustment depending on body weight is not required (see section “Pharmacological properties”).

Ethnicity

Dose adjustment depending on ethnicity is not required (see section “Pharmacological properties”).

Interaction

Special Instructions

The use of concomitant drugs

Rivaroxaban is not recommended for use in patients receiving concomitant systemic treatment with azole antifungals (e.g., ketoconazole) or HIV protease inhibitors (e.g., ritonavir). These drugs are potent inhibitors of CYP 3A4 and P-glycoprotein. Thus, these drugs may increase the plasma concentration of rivaroxaban to clinically significant values (2.6-fold on average), which may lead to an increased risk of bleeding (see section “Interaction with other medicinal products”). However, the azole antifungal drug fluconazole, a moderate CYP3A4 inhibitor, has a less pronounced effect on the exposure of rivaroxaban and can be used simultaneously with it (see section “Interaction with other medicinal products”).

Rivaroxaban should be used with caution in patients with moderate renal impairment (QClKr 30-49 mL/min) receiving concomitant medications that may increase plasma concentrations of rivaroxaban (see “Interaction with other drugs. section “Interaction with other medicinal products”).

In patients with severe renal dysfunction (KlKr<30 ml/min), the plasma concentration of rivaroxaban may be significantly elevated (1.6-fold on average), which may lead to an increased risk of bleeding. Therefore, due to the presence of the specified underlying disease, such patients have an increased risk of developing both bleeding and thrombosis. Due to limited clinical data, rivaroxaban should be used with caution in patients with CLR of 15-29 ml/min.

There are no clinical data on the use of rivaroxaban in patients with severe renal impairment (KlKr<15 ml/min). Therefore, rivaroxaban is not recommended for use in these patients (see sections “Dosage and administration”, “Pharmacological properties”).
Patients with severe renal dysfunction (CLR 15-29 ml/min) or increased risk of bleeding, as well as patients receiving concomitant systemic treatment with azole antifungal drugs or HIV protease inhibitors should be closely monitored for signs of bleeding after initiation of treatment. Follow-up can be accomplished by regular physical examination of patients, close monitoring of postoperative wound drainage, and periodic hemoglobin determination.

Patients with a history of stroke and/or TIA

The administration of Xarelto® twice daily at a dose of 2.5 mg is contraindicated in patients with ACS who have a history of stroke or TIA. Only a few ACS patients with a history of stroke or TIA have been studied, but the limited data demonstrate no clinical benefit from rivaroxaban treatment in these patients.

Patients with a history of hemorrhagic or lacunar stroke

Patients with CHD or TIA with a history of hemorrhagic or lacunar stroke have not been studied. Treatment with Xarelto® 2.5 mg twice daily in combination with acetylsalicylic acid is contraindicated in these patients.

Patients with ischemic nonlacunar stroke

Patients with CHD or OSA who had an ischemic nonlacunar stroke in the previous month have not been studied. Treatment with Xarelto® 2.5 mg twice daily in combination with acetylsalicylic acid is contraindicated in such patients during the first month after stroke.

Risk of bleeding

The drug Xarelto®, like other antithrombotic agents, should be used with caution in patients at increased risk of bleeding, such as:

Contraindications

Side effects

Table 2: Frequency of bleeding and anemia in patients treated with Xarelto® from phase III studies

Overdose

Pregnancy use