Xarelto, 28 pcs., 15 mg, film-coated tablets

Instructions for use XARELTO® (XARELTO)

Xarelto® 15 mg and 20 mg should be taken with food.

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

The recommended dose is 20 mg 1 time/day, daily. For patients with moderate renal failure (creatinine clearance <50-30 ml/min)

The recommended dose of the drug is 15 mg 1 time/day, daily.

Treatment should be continued as long as the risk factors for stroke and systemic thromboembolism persist.

If a dose is missed, the patient should immediately take Xarelto® and continue taking the drug regularly the next day in accordance with the recommended regimen. You should not double the dose you take to compensate for a previously missed dose.

The recommended maximum daily dose of the drug is 20 mg.

Treatment of deep vein thrombosis and prevention of recurrent DVT and pulmonary embolism (PE)

The recommended initial dose of the drug is 15 mg 2 times a day for the first 3 weeks, followed by Xarelto 20 mg 1 time a day for long-term therapy and prevention of recurrent DVT or PE.

Treatment should be continued as long as risk factors for venous thromboembolism persist.

It is recommended to adhere to a regular regimen of taking the drug. If a dose is missed while taking a dose of 15 mg 2 times a day, the patient should immediately take Xarelto® in order to ensure the delivery of the daily dose of 30 mg. To do this, you can take 2 tablets at the same time. (15 mg each). The next day, you should continue taking the drug regularly at a dose of 15 mg 2 times a day in accordance with the recommended regimen.

If a dose is missed while taking the 20 mg dose, the patient should immediately take Xarelto® to ensure the daily dose of 20 mg is supplied. The next day, you should continue taking the drug regularly at a dose of 20 mg 1 time / day in accordance with the recommended regimen.

The recommended maximum daily dose of the drug is 30 mg during the first 3 weeks of treatment.

In the subsequent treatment phase, the recommended maximum dose of the drug is 20 mg.

Additional information on specific patient groups

Patients with liver dysfunction

Xarelto® is contraindicated in patients with liver disease

accompanied by coagulopathy, which causes a clinically significant risk of bleeding.
Patients with other liver diseases do not require dosage changes. Available limited clinical data obtained for patients with moderate hepatic impairment (class B according to the Child-Pugh classification)
indicate a significant increase in the pharmacological activity of the drug.
For patients with severe hepatic impairment (Child-Pugh class C),
clinical data are not available.

Patients with impaired renal function

For the prevention of stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation

When prescribing Xarelto® to patients with mild renal failure (creatinine clearance <80-50 ml/min)

no dose adjustment is required.
For patients with moderate renal failure (creatinine clearance <50-30 ml/min)
, the recommended dose is 15 mg 1 time/day.
The limited clinical data available in patients with severe renal impairment (creatinine clearance < 30-15 ml/min)
demonstrate a significant increase in rivaroxaban concentrations in these patients.
For the treatment of this category of patients, Xarelto® 15 mg should be used with caution. The use of Xarelto® is not recommended in patients with CC < 15 ml/min
.

In patients for the treatment of deep vein thrombosis and prevention of recurrent DVT and PE

When prescribing Xarelto® to patients with mild renal failure (creatinine clearance < 80-50 ml/min) or moderate renal failure (creatinine clearance < 50-30 ml/min)

no dose adjustment is required.
The limited clinical data available in patients with severe renal impairment (creatinine clearance < 30-15 ml/min)
demonstrate a significant increase in rivaroxaban concentrations in these patients.
To treat this category of patients, Xarelto® should be used with caution. The use of Xarelto® is not recommended in patients with CC <15 ml/min
.

Switching from vitamin K antagonists (VKAs) to Xarelto® for the prevention of stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation

If MHO≤3, treatment with VKA should be stopped and treatment with Xarelto® should be started. When switching patients from VKA to Xarelto®, MHO values ​​will be erroneously elevated after taking Xarelto®. MHO is not suitable for determining the anticoagulant activity of Xarelto® and should therefore not be used for this purpose.

Switching from vitamin K antagonists to Xarelto® in patients for the treatment of DVT and prevention of recurrent DVT and PE

If MHO≤2.5, treatment with VKA should be stopped and treatment with Xarelto® should be started. When switching patients from VKA to Xarelto®, MHO values ​​will be erroneously elevated after taking Xarelto®. MHO is not suitable for determining the anticoagulant activity of Xarelto® and should therefore not be used for this purpose.

Switching from Xarelto® to vitamin K antagonists

There is a possibility of insufficient anticoagulant effect when switching from Xarelto® to VKA. In this regard, it is necessary to ensure a continuous sufficient anticoagulant effect during such a transition using alternative anticoagulants. It should be noted that Xarelto® may help increase MHO.

When switching from Xarelto® to VKA, VKA should be taken concomitantly until MHO reaches ≥2. During the first two days of the transition period, a standard dose of VKA should be used, followed by a dose of VKA depending on the results of the MHO determination. While taking Xarelto® and VKA, MHO should be determined no earlier than 24 hours after taking the previous dose, but before taking the next dose of Xarelto®.

A reliable determination of MHO can be carried out 24 hours after stopping the use of Xarelto® and taking the last dose of the drug.

Switching from parenteral anticoagulants to Xarelto®

For patients receiving parenteral anticoagulants, the use of Xarelto should be started 0-2 hours before the time of the next scheduled parenteral administration of the drug (for example, low molecular weight heparin) or at the time of discontinuation of continuous parenteral administration of the drug (for example, intravenous administration of unfractionated heparin).

Switching from Xarelto® to parenteral anticoagulants

Discontinue Xarelto® and administer the first dose of the parenteral anticoagulant at the time the next dose of Xarelto® is due.

Childhood

Safety and effectiveness in children and adolescents under 18 years of age

not installed.

Elderly patients, gender, weight or ethnicity

No dose adjustment is required in these categories of patients.

Compound

Side effects

The safety of Xarelto® was assessed in four phase III studies involving 6097 patients undergoing major lower extremity orthopedic surgery (total knee or total hip replacement) and 3997 medically hospitalized patients treated with Xarelto® 10 mg for up to 39 days. and in three phase III studies for the treatment of VTE, including 4566 patients who received either 15 mg Xarelto® twice daily for 3 weeks, followed by 20 mg once daily, or 20 mg once daily before 21 months

In addition, two phase III studies, including 7,750 patients, provided safety data in patients with non-valvular atrial fibrillation who received at least one dose of Xarelto® for up to 41 months, as well as 10,225 patients with acute coronary artery disease. syndrome, receiving at least one dose of 2.5 mg (2 times a day) or 5 mg (2 times a day) Xarelto® in addition to therapy with acetylsalicylic acid or acetylsalicylic acid with clopidogrel or ticlopidine, treatment duration up to 31 months.

Given the mechanism of action, the use of Xarelto may be accompanied by an increased risk of latent or overt bleeding from any organs and tissues, which can lead to posthemorrhagic anemia. The risk of bleeding may increase in patients with uncontrolled arterial hypertension and/or when used together with drugs that affect hemostasis (see "Contraindications", subsection WITH CAUTION). Signs, symptoms, and severity (including possible death) vary depending on the location, intensity, or duration of bleeding and/or anemia (see Overdose).

Hemorrhagic complications can manifest as weakness, pallor, dizziness, headache, shortness of breath, as well as enlargement of the limb or shock, which cannot be explained by other reasons. In some cases, symptoms of myocardial ischemia, such as chest pain and angina, developed as a result of anemia. Known complications secondary to severe bleeding, such as compartment syndrome and renal failure due to hypoperfusion, have also been reported with the use of Xarelto®. Therefore, the possibility of bleeding should be considered when assessing any patient receiving anticoagulants.

A summary of the incidence of adverse reactions reported for Xarelto® is provided below. In groups divided by frequency, adverse effects are presented in order of decreasing severity as follows: often - from ≥1 to <10% (from ≥1/100 to <1/10); uncommon - from ≥0.1 to <1% (from ≥1/1000 to <1/100); rarely - from ≥0.01 to <0.1% (from ≥1/10000 to <1/1000); very rarely - <0.01% (<1/10000).

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

From the circulatory and lymphatic system: often - anemia (including relevant laboratory parameters); uncommon - thrombocythemia (including increased platelet count)1.

From the heart: infrequently - tachycardia.

From the organ of vision: often - hemorrhage in the eye (including hemorrhage in the conjunctiva).

From the digestive system: often - bleeding gums, gastrointestinal bleeding (including rectal bleeding), pain in the gastrointestinal tract, dyspepsia, nausea, constipation1, diarrhea, vomiting1; Uncommon: dry mouth.

Systemic disorders and reactions at the site of drug administration: often - fever1, peripheral edema, deterioration in general health (including weakness, asthenia); uncommon - malaise (including anxiety); rarely - local swelling1.

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

From the immune system: rarely - allergic reactions, allergic dermatitis.

Injuries, poisoning and procedural complications: often - hemorrhages after procedures (including postoperative anemia and bleeding from a wound), excessive hematoma from a bruise; infrequently - discharge from the wound1; rarely - vascular pseudoaneurysm3.

Research results: often - increased transaminase activity; uncommon - increased bilirubin concentration, increased activity of ALP1, LDH1, lipase1, amylase1, GGT1; rarely - an increase in the concentration of conjugated bilirubin (with or without a concomitant increase in ALT activity).

From the musculoskeletal system and connective tissue: often - pain in the extremities1; infrequently - hemarthrosis; rarely - hemorrhage into the muscles.

From the nervous system: often - dizziness, headache; infrequently - intracerebral and intracranial hemorrhage, short-term fainting.

From the kidneys and urinary tract: often - bleeding from the urogenital tract (including hematuria and menorrhagia2), renal failure (including increased levels of creatinine, urea)1.

From the respiratory tract: often - nosebleeds, hemoptysis.

From the skin and subcutaneous tissues: often - itching (including rare cases of generalized itching), rash, ecchymosis, skin and subcutaneous hemorrhages; infrequently - urticaria.

From the side of blood vessels: often - hypotension, hematoma.

1Registered after major orthopedic operations.

2Recorded in the treatment of VTE as very common in women under 55 years of age.

3Recorded as uncommon in the prevention of sudden death and myocardial infarction in patients after ACS (after percutaneous interventions).

During post-marketing monitoring, cases of the following adverse reactions, the development of which had a temporary relationship with taking Xarelto, were reported. It is not possible to assess the frequency of occurrence of such adverse reactions within the framework of post-registration monitoring.

From the immune system: angioedema, allergic edema. In phase III randomized clinical trials (RCTs), such adverse events were considered uncommon (≥1/1000 to <1/100).

From the liver: cholestasis, hepatitis (including hepatocellular damage). In the phase III RCT, these adverse events were considered rare (≥1/10,000 to <1/1,000).

From the circulatory and lymphatic system: thrombocytopenia. In the phase III RCT, these adverse events were considered uncommon (≥1/1000 to <1/100).

From the musculoskeletal system and connective tissue: frequency unknown - increased subfascial pressure syndrome (compartment syndrome) due to hemorrhage into the muscles.

From the kidneys and urinary tract: frequency unknown - renal failure/acute renal failure due to bleeding leading to renal hypoperfusion.

Use during pregnancy and breastfeeding

The effectiveness and safety of Xarelto® in pregnant women have not been established.

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

Due to the possible risk of bleeding and ability to cross the placenta, rivaroxaban is contraindicated during pregnancy.

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

There are no data on the use of Xarelto® for the treatment of women during breastfeeding. Data obtained in experimental animals show that rivaroxaban is excreted in breast milk. Rivaroxaban can be used only after breastfeeding has been stopped (see “Contraindications”).

Fertility. Studies have shown that rivaroxaban does not affect male or female fertility in rats. No studies have been conducted on the effects of rivaroxaban on fertility in humans.

Description of the dosage form

Film-coated tablets, 15 mg: round, biconvex, pink-brown; An engraving is applied using the extrusion method: on one side there is a triangle with the dosage designation (15), on the other there is a branded Bayer cross.

The appearance of the tablet at the break: a homogeneous white mass surrounded by a pink-brown shell.

Film-coated tablets, 20 mg: round, biconvex, red-brown; An engraving is applied by extrusion: on one side there is a triangle with the dosage designation (20), on the other there is a branded Bayer cross.

Broken appearance of the tablet: a homogeneous white mass surrounded by a red-brown shell.