When is the best time to take Xarelto? How to use Xarelto. Use in old age

Xarelto: trust, practice-based

Xarelto®: confidence based on randomized trials and real-world clinical practice 1,2

Experience practical application Xarelto® for 7 indications in more than 18 million patients 2,3

Xarelto® is the most commonly prescribed new oral anticoagulant in the world

Xarelto 20 mg 15 mg - instructions for use

Registration number: LP-001457

Trade name

International generic name : rivaroxaban

Chemical name: 5-Chloro-N-(((5S)-2-oxo-3--1,3-oxazolidin-5-yl)methyl)-2-thiophenecarboxamide

Dosage form: coated tablets film-coated

Compound:

One film-coated tablet contains:
Active substance: rivaroxaban micronized 15 mg or 20 mg,
Excipients: microcrystalline cellulose – 37.50 mg or 35.00 mg, croscarmellose sodium – 3.00 mg, hypromellose 5cP – 3.00 mg, lactose monohydrate – 25.40 mg or 22.90 mg, magnesium stearate – 0.60 mg, sodium lauryl sulfate – 0.50 mg; shell: iron oxide red - 0.150 mg or 0.350 mg, hypromellose 15cP - 1.50 mg, macrogol 3350 - 0.50 mg, titanium dioxide - 0.350 mg or 0.150 mg, respectively.

Description

Tablets 15 mg: round, biconvex, pink-brown, film-coated tablets; 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.
Tablets 20 mg: round, biconvex, red-brown, film-coated tablets; An engraving is applied using the extrusion method: 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.

Pharmacotherapeutic group: direct factor Xa inhibitors

ATX Code: В01AF01

Pharmacological properties

Pharmacodynamics
Mechanism of action
Rivaroxaban is a highly selective direct factor Xa inhibitor with high oral bioavailability.
Activation of factor X to form factor Xa through the intrinsic and extrinsic coagulation pathways plays a central role in the coagulation cascade.
Pharmacodynamic effects
In humans, dose-dependent inhibition of factor Xa was observed. Rivaroxaban has a dose-dependent effect on prothrombin time and correlates well with plasma concentrations (r=0.98) when the Neoplastin ® kit is used for analysis. Results will vary if other reagents are used. Prothrombin time should be measured in seconds because the INR (International Normalized Ratio) is calibrated and certified only for coumarin derivatives and cannot be used for other anticoagulants.
In patients with nonvalvular atrial fibrillation taking rivaroxaban for the prevention of stroke and systemic thromboembolism, the 5/95th percentile for prothrombin time (Neoplastin ® ) 1 to 4 hours after tablet dosing (i.e., at maximum effect) ranges from 14 to 40 seconds in patients taking 20 mg once daily and 10 to 50 seconds in patients with renal impairment (creatinine clearance 49 to 30 mL/min) taking 15 mg once daily.
In patients receiving rivaroxaban for the treatment and prevention of recurrent deep vein thrombosis (DVT) and thromboembolism pulmonary artery(PE), 5/95 percentiles for prothrombin time (Neoplastin®) 2 to 4 hours after tablet dosing (i.e., at maximum effect) range from 17 to 32 seconds in patients taking 15 mg twice daily, and 15 to 30 seconds in patients taking 20 mg once daily.
Also, rivaroxaban dose-dependently increases activated partial thromboplastin time (aPTT) and HepTest ® result; however, these parameters are not recommended for assessing the pharmacodynamic effects of rivaroxaban.
Also, if clinically warranted, rivaroxaban concentrations can be measured using a calibrated quantitative anti-factor Xa test.
During treatment with Xarelto ®, monitoring of blood coagulation parameters is not required.
In healthy men and women over 50 years of age, prolongation of the electrocardiogram QT interval under the influence of rivaroxaban was not observed.
Pharmacokinetics
Absorption and bioavailability
The absolute bioavailability of rivaroxaban after taking a dose of 10 mg is high (80-100%).
Rivaroxaban is rapidly absorbed; the maximum concentration (Cmax) is achieved 2-4 hours after taking the tablet.
When taking rivaroxaban at a dose of 10 mg with food, there was no change in AUC (area under the concentration-time curve) and C max (maximum concentration). The pharmacokinetics of rivaroxaban is characterized by moderate individual variability; individual variability (variation coefficient) ranges from 30 to 40%.
Due to the reduced degree of absorption, a bioavailability of 66% was observed when taking 20 mg on an empty stomach. When Xarelto 20 mg was taken with food, there was a 39% increase in mean AUC compared to fasting, indicating almost complete absorption and high bioavailability.
The absorption of rivaroxaban depends on the site of release in the gastrointestinal (GI) tract. A 29% and 56% reduction in AUC and Cmax, respectively, compared to whole tablet administration, was observed when rivaroxaban granules were distally released small intestine or ascending colon. Administration of rivaroxaban should be avoided. gastrointestinal tract distal to the stomach, as this may reduce absorption and, accordingly, exposure of the drug.
The study assessed the bioavailability (AUC and Cmax) of 20 mg rivaroxaban taken orally as a crushed tablet mixed with applesauce or suspended in water, or given by gastric tube followed by a liquid diet, compared with administration of a whole tablet. The results demonstrated a predictable dose-dependent pharmacokinetic profile for rivaroxaban, with bioavailability at the above dosing levels consistent with lower doses of rivaroxaban.
Distribution
In the human body, most of rivaroxaban (92-95%) is bound to plasma proteins, the main binding component being serum albumin. The volume of distribution is moderate, V ss is approximately 50 l.
Metabolism and excretion
When taken orally, approximately 2/3 of the prescribed dose of rivaroxaban is metabolized and subsequently excreted in equal parts through the urine and intestines. The remaining 1/3 of the dose is eliminated unchanged by direct renal excretion, mainly due to active renal secretion.
Rivaroxaban is metabolized through isoenzymes CYP3A4, CYP2J2, as well as through 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 received in vitro, Rivaroxaban is a substrate for the transporter proteins P-gp (P-glycoprotein) and Bcrp (breast cancer resistance protein).
Unchanged rivaroxaban is the only active compound in human plasma, and no major or active circulating metabolites have been detected in plasma. Rivaroxaban, whose systemic clearance is approximately 10 L/h, can be classified as a drug with low clearance. When rivaroxaban is eliminated from plasma, the terminal half-life is 5 to 9 hours in younger patients and 11 to 13 hours in older patients.
Gender/Old age (over 65 years old)
Elderly patients have higher plasma concentrations of rivaroxaban than younger patients; the mean AUC value is approximately 1.5 times higher than in younger patients, mainly due to an apparent decrease in total and renal clearance.
No clinically significant differences in pharmacokinetics were found between men and women.
Body mass
Too little or too much body weight (less than 50 kg and more than 120 kg) only slightly affects the concentration of rivaroxaban in the blood plasma (the difference is less than 25%).
Childhood
There are no data available for this age category.
Interethnic differences
There were no clinically significant differences in pharmacokinetics and pharmacodynamics in patients of Caucasian, African American, Hispanic, Japanese or Chinese ethnicity.
Liver dysfunction
The effect of hepatic impairment on the pharmacokinetics of rivaroxaban was studied in patients allocated according to the Child-Pugh classification (according to standard procedures in clinical trials). The Child-Pugh classification allows you to evaluate the prognosis chronic diseases liver, mainly cirrhosis. In patients undergoing anticoagulant therapy, the most important consequence of impaired liver function is a decrease in the synthesis of coagulation factors in the liver. Since this indicator corresponds to only one of the five clinical/biochemical criteria that make up the Child-Pugh classification, the risk of bleeding does not clearly correlate with this classification. The question of treating such patients with anticoagulants should be decided regardless of the Child-Pugh class.
Xarelto ® is contraindicated in patients with liver disease associated with coagulopathy causing a clinically significant risk of bleeding.
In patients with liver cirrhosis and mild degree liver failure (Child-Pugh class A), the pharmacokinetics of rivaroxaban differed only slightly from the corresponding indicators in the control group of healthy subjects (on average, there was an increase in the AUC of rivaroxaban by 1.2 times). There were no significant differences in pharmacodynamic properties between groups.
In patients with liver cirrhosis and liver failure moderate severity (Child-Pugh class B), the mean AUC of rivaroxaban was significantly increased (2.3-fold) compared with healthy volunteers due to significantly reduced clearance medicinal substance, which indicates serious illness liver. The suppression of factor Xa activity was more pronounced (2.6 times) than in healthy volunteers. Prothrombin time was also 2.1 times higher than in healthy volunteers. By measuring prothrombin time, the extrinsic coagulation pathway is assessed, including coagulation factors VII, X, V, II and I, which are synthesized in the liver. Patients with moderate hepatic impairment are more sensitive to rivaroxaban, which is a consequence of a closer relationship between pharmacodynamic effects and pharmacokinetic parameters, especially between concentration and prothrombin time.
There are no data available for patients with Child-Pugh Class C hepatic impairment.
Renal dysfunction
In patients with renal insufficiency, an increase in rivaroxaban exposure was observed, inversely proportional to the degree of decrease in renal function, as assessed by creatinine clearance.
In patients with renal failure with creatinine clearance 80-50 ml/min, creatinine clearance 49-30 ml/min and creatinine clearance 29-15 ml/min, 1.4-, 1.5- and 1.6-fold increases in concentrations were observed rivaroxaban plasma concentrations (AUC), respectively, compared with healthy volunteers.
The corresponding increase in pharmacodynamic effects was more pronounced.
In patients with a creatinine clearance of 80-50 ml/min, a creatinine clearance of 49-30 ml/min and a creatinine clearance of 29-15 ml/min, the overall suppression of factor Xa activity increased by 1.5, 1.9 and 2 times compared with healthy subjects volunteers; 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 a creatinine clearance of 29-15 ml/min are 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 creatinine clearance< 15 мл/мин отсутствуют, в связи с чем не рекомендуется применять препарат у данной категории пациентов.

Indications for use

• prevention of stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation;
• treatment of deep vein thrombosis and pulmonary embolism and prevention of relapses of DVT and PE.

Contraindications

• hypersensitivity to rivaroxaban or any excipients contained in the tablet;
• clinically significant active bleeding (eg, intracranial hemorrhage, gastrointestinal bleeding);
• injury or condition associated with an increased risk of major bleeding, such as a current or recent gastrointestinal ulcer, the presence malignant tumors With high risk bleeding, recent brain or spinal cord injuries, brain surgery, spinal cord or eyes, intracranial hemorrhage, diagnosed or suspected esophageal varices, arteriovenous malformations, vascular aneurysms or vascular pathology of the brain or spinal cord;
• concomitant therapy with any other anticoagulants, for example, unfractionated heparin, low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, apixaban, dabigatran, etc.), except in cases of transition from or rivaroxaban (see section "Method of administration and dosage") or when using unfractionated heparin in doses necessary to ensure the functioning of a central venous or arterial catheter;
• liver diseases occurring with coagulopathy, which causes a clinically significant risk of bleeding;
• pregnancy and period breastfeeding;
• children and adolescents up to 18 years of age (efficacy and safety in patients of this age group have not been established);
• renal failure(creatinine clearance< 15 мл/мин) (клинические данные о применении ривароксабана у данной категории пациентов отсутствуют);
• congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption (due to the presence of lactose in the composition).

Carefully

The drug should be used with caution:

• When treating patients with an increased risk of bleeding (including congenital or acquired bleeding tendency, uncontrolled severe arterial hypertension, peptic ulcer stomach and duodenum in the acute stage, recent peptic ulcer of the stomach and duodenum, vascular retinopathy, bronchiectasis or history of pulmonary hemorrhage);
• In the treatment of patients with renal failure (creatinine clearance 49-30 ml/min) who are simultaneously receiving drugs that increase the concentration of rivaroxaban in the blood plasma (see section “Interacting with Others” medicines and other forms of interaction");
• When treating patients with renal failure (creatinine clearance 29-15 ml/min), caution should be exercised, since the concentration of rivaroxaban in the blood plasma in such patients may increase significantly (on average 1.6 times), and as a result they are susceptible to increased risk of bleeding;
• In patients receiving medications that affect hemostasis (for example, NSAIDs, antiplatelet agents or other antithrombotic agents);
• Xarelto ® is not recommended for use in patients receiving systemic treatment antifungal drugs azole group (eg, ketoconazole) or HIV protease inhibitors (eg, ritonavir). These drugs are strong inhibitors of the CYP3A4 isoenzyme and P-glycoprotein. As a result, these drugs may increase the plasma concentrations of riva-roxaban to clinical levels. significant level(on average 2.6 times), which increases the risk of bleeding. The azole antifungal drug fluconazole, a moderate inhibitor of CYP3A4, has a less pronounced effect on the exposure of rivaroxaban and can be used concomitantly with it (see section “Interaction with other medicinal products and other forms of interaction”).
• Patients with renal impairment (creatinine clearance 29-15 ml/min) or an increased risk of bleeding and patients receiving concomitant systemic treatment with azole antifungals or HIV protease inhibitors should be closely monitored after initiation of treatment for timely detection of bleeding complications.

Use during pregnancy and breastfeeding

Pregnancy
The safety and effectiveness 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 pharmacological action 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, Xarelto ® is contraindicated during pregnancy.
Women with preserved reproductive capacity should use effective methods contraception during treatment with Xarelto ® .
Breast-feeding
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. Xarelto ® can only be used after stopping breastfeeding (see section “Contraindications”).
Fertility
Studies have shown that rivaroxaban does not affect male or female fertility in rats. There are no human studies of the effects of rivaroxaban on fertility.

Directions for use and doses

Inside. Xarelto ® 15 mg and 20 mg should be taken with food.
If the patient is unable to swallow the tablet whole, the Xarelto ® tablet may be crushed and mixed with water or a liquid meal, such as applesauce, immediately before dosing. After taking crushed Xarelto ® 15 mg or 20 mg tablets, you should immediately eat.
A crushed Xarelto ® tablet may be given through a gastric tube. The position of the probe in the gastrointestinal tract must be further 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 a small amount of water must be introduced in order to wash off any remaining drug from the walls of the tube. After taking crushed Xarelto ® 15 mg or 20 mg tablets, you must immediately receive enteral nutrition.
Prevention of stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation
The recommended dose is 20 mg once daily.
For patients with impaired renal function (creatinine clearance 49-30 ml/min), the recommended dose is 15 mg once daily.
The recommended maximum daily dose is 20 mg.
Duration of treatment: Xarelto ® therapy should be considered as a long-term treatment, continued as long as the benefits of treatment outweigh the risks possible complications (see sections “With caution” and “Special instructions”).

If the reception next dose 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.
Treatment of DVT and PE and prevention of recurrence of DVT and PE
The recommended starting dose for the treatment of acute DVT or PE is 15 mg twice daily for the first 3 weeks, followed by 20 mg once daily for further treatment and prevention of recurrent DVT and PE.
The maximum daily dose is 30 mg during the first 3 weeks of treatment and 20 mg during further treatment.
The duration of treatment is determined individually after carefully weighing the benefits of treatment against the risk of bleeding. The minimum duration of treatment (at least 3 months) should be based on an assessment regarding reversible risk factors (i.e. previous surgical intervention, injury, period of immobilization). The decision to extend the course of treatment for more long time based on assessment regarding persistent risk factors or in the event of development of idiopathic DVT or PE.
What to do if you miss a dose
It is important to adhere to the established dosage regimen.
If a dose is missed on the 15 mg twice daily dosing regimen, the patient should immediately take Xarelto to achieve daily dose 30 mg. Thus, two 15 mg tablets can be taken at one time. The next day, the patient should continue taking the drug regularly in accordance with the recommended regimen.
If a dose is missed on the 20 mg once daily dosing regimen, the patient should immediately take Xarelto ® and continue taking the drug regularly as recommended the next day.
Selected patient groups
No dose adjustment is required depending on the patient's age (over 65 years), gender, body weight or ethnicity.
Patients with liver dysfunction
Xarelto ® is contraindicated in patients with liver disease associated with coagulopathy that carries a clinically significant risk of bleeding (see section “Contraindications”).
Patients with other liver diseases do not require dosage changes (see section " Pharmacological properties/ Pharmacokinetics").
Available limited clinical data obtained in patients with moderate hepatic impairment (class B according to the Child-Pugh classification) indicate a significant increase in the pharmacological activity of the drug. In patients with severe hepatic impairment (Child-Pugh class C), no clinical data are available.
Patients with impaired renal function
When prescribing Xarelto ® to patients with renal failure (creatinine clearance 80-50 ml/min), no dose adjustment is required.
For the prevention of stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation with renal failure (creatinine clearance 49-30 ml/min), the recommended dose is 15 mg once daily.
When treating DVT and PE and preventing recurrence of DVT and PE in patients with renal failure (creatinine clearance 49-30 ml/min), no dose adjustment is required.
The limited clinical data available demonstrate a significant increase in rivaroxaban concentrations in patients with renal failure (creatinine clearance 29-15 ml/min). To treat this category of patients, Xarelto ® should be used with caution.
The use of Xarelto ® is not recommended in patients with creatinine clearance< 15 мл/мин (see sections “Contraindications”, “Pharmacological properties / Pharmacokinetics”).
Switching from vitamin K antagonists (VKA) to Xarelto ®
When preventing stroke and systemic thromboembolism, treatment with VKA should be stopped and treatment with Xarelto ® should be started if the INR is ≤ 3.0.
For DVT and PE, treatment with VKA should be discontinued and treatment with Xarelto ® should be started if the INR is ≤ 2.5.
When switching patients from VKA to Xarelto ® , after taking Xarelto ® , INR values ​​will be erroneously high. INR 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 (VKAs)
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 the INR. Patients switching from Xarelto ® to a VKA should take a VKA concomitantly until the INR reaches ≥ 2.0. During the first two days of the transition period, a standard dose of VKA should be used, followed by a dose of VKA determined depending on the INR value. Therefore, during concomitant use of Xarelto ® and VKA, the 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 ®, the INR value can be reliably determined 24 hours after the last dose. (see "Interaction with other medicinal products and other forms of interaction").
Switching from parenteral anticoagulants to Xarelto ®
In patients receiving parenteral anticoagulants, Xarelto should be started 0-2 hours before the next scheduled parenteral dose (eg, low molecular weight heparin) or at the time of discontinuation of continuous parenteral administration of the drug (for example, intravenous administration 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.
Cardioversion for the prevention of stroke and systemic thromboembolism
Treatment with Xarelto ® may be initiated or continued in patients who may require cardioversion. For transesophageal echocardiography (TEE)-guided cardioversion in patients who have not previously received anticoagulation therapy, treatment with Xarelto should be initiated at least 4 hours before cardioversion to ensure adequate anticoagulation.

Side effect

The safety of Xarelto ® was assessed in four phase III studies involving 6097 patients undergoing major orthopedic surgery lower limbs(total knee replacement or hip joint) and 3997 patients hospitalized for medical reasons treated with Xarelto ® 10 mg for up to 39 days, as well as in three phase III treatment studies venous thromboembolism included 4,556 patients who received either 15 mg of Xarelto ® twice daily for 3 weeks followed by 20 mg once daily or 20 mg once daily for up to 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 ACS. who received at least one dose of 2.5 mg (twice daily) or 5 mg (twice daily) Xarelto ® in addition to therapy 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 hidden 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 joint use with drugs that affect hemostasis (See section "With caution"). Signs, symptoms and severity (including possible death) vary depending on the location, intensity or duration of bleeding and/or anemia (see section "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 given below. In groups divided by frequency, adverse effects are presented in order of decreasing severity, as follows:
Common: ≥1% to<10% (от ≥1/100 до <1/10),
Uncommon: ≥0.1% to<1% (от ≥1/1000 до <1/100),
Rare: ≥0.01% to<0,1% (от ≥1/10000 до <1/1000),
Very rarely:<0,01% (<1/10000).
All adverse reactions that occurred during treatment in patients participating in phase III clinical trials
Disorders of the circulatory and lymphatic system
Often: anemia (including relevant laboratory parameters)
Infrequently: thrombocythemia (including elevated platelet counts)*
Heart disorders
Infrequently: tachycardia
Visual disorders
Often: hemorrhage in the eye (including hemorrhage into the conjunctiva)
Digestive system disorders
Often: bleeding gums, gastrointestinal bleeding (including rectal bleeding), pain in the gastrointestinal tract, dyspepsia, nausea, constipation*, diarrhea, vomiting*
Infrequently: dry mouth
Systemic disorders and reactions at the injection site
Often: fever*, peripheral edema, decreased overall muscle strength and tone (including weakness, asthenia)
Infrequently: deterioration in general health (including malaise)
Rarely: local swelling*
Liver disorders
Infrequently: liver dysfunction
Rarely: jaundice
Immune system disorders
Infrequently: allergic reaction, allergic dermatitis
Injuries, poisonings and procedural complications
Often: hemorrhages after procedures (including postoperative anemia and bleeding from the wound), excessive hematoma due to bruise
Infrequently: discharge from the wound*
Rarely: Vascular pseudoaneurysm***
Research results
Often: increased activity of “liver” transaminases
Infrequently: increased bilirubin concentration, increased alkaline phosphatase activity*, increased LDH activity*, increased lipase activity*, increased amylase activity*, increased GGT activity*
Rarely: increased concentration of conjugated bilirubin (with or without a concomitant increase in ALT activity)
Musculoskeletal and connective tissue disorders
Often: pain in limbs*
Infrequently: hemarthrosis
Rarely: muscle hemorrhage
Nervous system disorders
Often: dizziness, headache
Infrequently: intracerebral and intracranial hemorrhages, short-term fainting
Renal and urinary tract disorders
Often: bleeding from the urogenital tract (including hematuria and menorrhagia**), renal failure (including increased creatinine levels, increased urea levels)*
Respiratory disorders
Often: nosebleeds, hemoptysis
Skin and subcutaneous tissue disorders
Often: pruritus (including rare cases of generalized pruritus), rash, ecchymosis, cutaneous and subcutaneous hemorrhages
Infrequently: hives
Vascular disorders
Often: marked decrease in blood pressure, hematoma
*registered after major orthopedic surgeries
** reported in the treatment of VTE as very common in women< 55 лет
*** were registered 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 had a temporary connection with the use of Xarelto ® . It is not possible to assess the frequency of occurrence of such adverse reactions within the framework of post-registration monitoring.
Immune system disorders: angioedema, allergic edema. In the phase III RCT, such adverse events were assessed as uncommon (from >1/1000 to<1/100).
Liver disorders: cholestasis, hepatitis (including hepatocellular damage). In the phase III RCT, such adverse events were assessed as rare (from >1/10000 to<1/1000).
Disorders of the circulatory and lymphatic system: thrombocytopenia. In the phase III RCT, such adverse events were assessed as uncommon (from >1/1000 to<1/100).
Musculoskeletal and connective tissue disorders: frequency unknown– syndrome of increased subfascial pressure (compartment syndrome) due to hemorrhage into the muscles.
Renal and urinary tract disorders: frequency unknown– renal failure/acute renal failure due to bleeding leading to renal hypoperfusion.

Overdose

Rare cases of overdose have been reported when taking rivaroxaban up to 600 mg without bleeding or other adverse reactions. Due to limited absorption, the development of a low-level plateau in drug concentration is expected without a further increase in its average plasma concentration when using doses exceeding therapeutic doses of 50 mg and above.
The specific antidote for rivaroxaban is unknown. In case of overdose, activated charcoal can be used to reduce the absorption of rivaroxaban. Given its extensive binding to plasma proteins, it is expected that rivaroxaban will not be eliminated during dialysis.
Treatment of bleeding
If a bleeding complication occurs in a patient receiving rivaroxaban, the next dose of the drug should be delayed or, if necessary, treatment with this drug should be discontinued. The half-life of rivaroxaban is approximately 5-13 hours. Treatment should be individualized depending on the severity and location of the bleeding. If necessary, appropriate symptomatic treatment can be used, such as mechanical compression (for example, for severe nosebleeds), surgical hemostasis with evaluation of its effectiveness, infusion therapy and hemodynamic support, the use of blood products (packed red blood cells or fresh frozen plasma, depending on the occurrence anemia or coagulopathy) or platelets.
If the above measures do not eliminate bleeding, specific reverse-acting procoagulant drugs may be prescribed, such as coagulation factors II, VII, IX and X in combination [Prothrombin complex], anti-inhibitory coagulant complex or eptacog alfa [activated]. However, at present, experience with the use of these drugs in patients receiving Xarelto ® is very limited.
Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban.
There is limited experience with the use of tranexamic acid and no experience with the use of aminocaproic acid and aprotinin in patients receiving Xarelto ® . There is no scientific basis for or experience with the use of the systemic hemostatic drug desmopressin in patients receiving Xarelto ® .

Interaction with other medicinal products and other forms of interaction

Pharmacokinetic interactions
Elimination of rivaroxaban occurs primarily through hepatic metabolism mediated by the cytochrome P450 system (CYP3A4, CYP2J2), as well as through renal excretion of unchanged drug using the P-gp/Bcrp (P-glycoprotein/breast cancer resistance protein) transporter systems. .
Rivaroxaban does not suppress or induce the CYP3A4 isoenzyme and other important cytochrome isoforms.
Concomitant use of Xarelto and potent inhibitors of CYP3A4 and P-glycoprotein may result in decreased renal and hepatic clearance of rivaroxaban and thus significantly increase its systemic exposure.
The combined use of Xarelto ® and the azole antifungal agent ketoconazole (400 mg 1 time per day), which is a potent 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 C max of rivaroxaban by 1.7 times , which was accompanied by a significant increase in the pharmacodynamic effect of the drug.
Co-administration of Xarelto ® and the HIV protease inhibitor ritonavir (600 mg 2 times daily), which is a potent 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. In this regard, Xarelto ® is not recommended for use in patients receiving systemic treatment with azole antifungals or HIV protease inhibitors (See section "With caution").
Clarithromycin (500 mg 2 times a day), a potent inhibitor of the CYP3A4 isoenzyme and a moderate inhibitor of P-glycoprotein, caused an increase in AUC values ​​by 1.5 times and Cmax of rivaroxaban by 1.4 times. This increase is in the order of normal variability in AUC and Cmax and is considered clinically insignificant.
Erythromycin (500 mg 3 times a day), a moderate inhibitor of the CYP3A4 isoenzyme and P-glycoprotein, caused an increase in the AUC and Cmax values ​​of rivaroxaban by 1.3 times. This increase is in the order of normal variability in AUC and Cmax and is considered clinically insignificant.
In patients with renal failure (creatinine clearance ≤80-50 ml/min), erythromycin (500 mg 3 times daily) caused an increase in rivaroxaban AUC by 1.8 times and C max by 1.6 times compared with patients with normal function kidneys that did not receive concomitant therapy. In patients with renal failure (creatinine clearance 49-30 ml/min), erythromycin caused an increase in rivaroxaban AUC values ​​by 2.0 times and C max by 1.6 times compared with patients with normal renal function who did not receive concomitant therapy (See section "With caution").
Fluconazole (400 mg once daily), a moderate inhibitor of the CYP3A4 isoenzyme, caused a 1.4-fold increase in the mean AUC of rivaroxaban and a 1.3-fold increase in the mean Cmax. This increase is in 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 coadministration.
Co-administration of Xarelto ® and rifampicin, a strong inducer of CYP3A4 and P-glycoprotein, resulted in a decrease in the mean AUC of rivaroxaban by approximately 50% and a parallel decrease in its pharmacodynamic effects. Concomitant use of rivaroxaban with other strong CYP3A4 inducers (eg, phenytoin, carbamazepine, phenobarbital or St. John's wort) may also result in decreased rivaroxaban plasma concentrations. The decrease in rivaroxaban plasma concentrations was considered clinically insignificant. Strong CYP3A4 inducers should be used with caution.
Pharmacodynamic interactions
After simultaneous use of enoxaparin sodium (single dose 40 mg) and Xarelto ® (single dose 10 mg), a additive effect was observed on anti-factor Xa activity, which was not accompanied by additional additive effects on blood clotting tests (prothrombin time, aPTT). Enoxaparin sodium did not change the pharmacokinetics of rivaroxaban (See section "With caution").
Due to the increased risk of bleeding, caution should be exercised when used together with any other anticoagulants. (see sections “Contraindications”, “With caution” and “Special instructions”).
No pharmacokinetic interaction was found between Xarelto ® (15 mg) and clopidogrel (loading dose 300 mg followed by a maintenance dose of 75 mg), but in a subgroup of patients a significant increase in bleeding time was found, which did not correlate with the degree of platelet aggregation and the content of P-selectin or GPIIb /IIIa receptor (See section "With caution").
After co-administration of Xarelto ® (15 mg) and naproxen 500 mg, no clinically significant increase in bleeding time was observed. However, a more pronounced pharmacodynamic response is possible in some individuals.
Caution should be exercised when using Xarelto ® together with NSAIDs (including acetylsalicylic acid) and platelet aggregation inhibitors, since the use of these drugs usually increases the risk of bleeding.
Switching patients from warfarin (INR 2.0 to 3.0) to Xarelto ® (20 mg) or from Xarelto ® (20 mg) to warfarin (INR 2.0 to 3.0) increased prothrombin time/INR (Neoplastin ) to a greater extent than would be expected from simple summation of effects (individual INR values ​​can be as high as 12), while the effects on APTT, factor Xa suppression, and endogenous thrombin potential were additive.
If it is necessary to study the pharmacodynamic effects of Xarelto ® during the transition period, anti-Xa activity, PiCT and HepTest ® can be used as necessary tests that are not affected by warfarin. Starting on the 4th day after stopping warfarin, all test results (including PT, APTT, factor Xa inhibition and EPT (endogenous thrombin potential)) reflect only the effect of Xarelto ® (see section "Method of administration and dosage").
If it is necessary to study the pharmacodynamic effects of warfarin during the transition period, measuring the INR value at Interim can be used. rivaroxaban (24 hours after the previous dose of rivaroxaban), since rivaroxaban has minimal effect on this indicator during this period.
No pharmacokinetic interactions have been reported between warfarin and Xarelto ® .
The drug interaction of Xarelto ® with the vitamin K antagonist (VKA) phenindione has not been studied. It is recommended, whenever possible, to avoid transferring patients from Xarelto ® therapy to VKA phenindione therapy and vice versa.
There is limited experience converting patients from VKA acenocoumarol therapy to Xarelto ® .
If there is a need to transfer a patient from Xarelto ® therapy to VKA therapy with phenindione or acenocoumarol, then special care should be taken; daily monitoring of the pharmacodynamic effect of the drugs (INR, prothrombin time) should be carried out immediately before taking the next dose of Xarelto ® .
If there is a need to transfer a patient from VKA therapy with phenindione or acenocoumarol to Xarelto ® therapy, then special care should be taken; monitoring of the pharmacodynamic effect of the drugs is not required.
Incompatibility
Unknown.
No interactions detected
No pharmacokinetic interactions have been identified between rivaroxaban and midazolam (CYP3A4 substrate), digoxin (P-gp substrate) or atorvastatin (CYP3A4 and P-gp substrate).
Co-administration with the proton pump inhibitor omeprazole, the H2 receptor antagonist ranitidine, aluminum hydroxide/magnesium hydroxide antacids, naproxen, clopidogrel or enoxaparin does not affect the bioavailability and pharmacokinetics of rivaroxaban.
No clinically significant pharmacokinetic or pharmacodynamic interactions were observed with the combined use of Xarelto ® and 500 mg of acetylsalicylic acid.
Effect on laboratory parameters
The drug Xarelto ® affects blood clotting parameters (PT, APTT, HepTest ®) due to its mechanism of action.

special instructions

The use of Xarelto ® is not recommended in patients receiving concomitant systemic treatment with azole antifungals (eg, ketoconazole) or HIV protease inhibitors (eg, ritonavir). These drugs are strong inhibitors of CYP3A4 and P-glycoprotein. Therefore, these drugs may increase rivaroxaban plasma concentrations to clinically significant levels (2.6-fold on average), which may result in an increased risk of bleeding.
However, the azole antifungal drug fluconazole, a moderate inhibitor of CYP3A4, has a less pronounced effect on rivaroxaban exposure and can be used concomitantly with it (see section "Interaction with other medicinal products and other forms of interaction").
Xarelto ® should be used with caution in patients with moderate renal impairment (creatinine clearance 49-30 ml/min) receiving concomitant medications that may lead to increased plasma concentrations of rivaroxaban (see section "Interaction with other medicinal products and other forms of interaction").
In patients with severe renal impairment (CK<30 мл/мин) концентрация ривароксабана в плазме может быть значительно повышенной (в 1,6 раза в среднем), что может привести к повышенному риску кровотечения. Поэтому, вследствие наличия указанного основного заболевания такие пациенты имеют повышенный риск развития как кровотечений, так и тромбозов. В связи с ограниченным количеством клинических данных препарат Ксарелто ® должен применяться с осторожностью у пациентов с КК 29-15 мл/мин.
Clinical data on the use of rivaroxaban in patients with severe renal impairment (CR)<15 мл/мин) отсутствуют. Поэтому применение препарата Ксарелто ® не рекомендуется у таких пациентов (see section "Method of administration and dosage", "Pharmacokinetics", "Pharmacodynamics").
Patients with severe renal impairment or an increased risk of bleeding, as well as patients receiving concomitant systemic treatment with azole antifungals or HIV protease inhibitors, should be closely monitored for signs of bleeding after initiation of treatment.
Xarelto ®, like other antithrombotic agents, should be used with caution in patients at increased risk of bleeding, including:

• patients with a congenital or acquired tendency to bleeding;
• patients with uncontrolled severe arterial hypertension;
• patients with gastric and duodenal ulcers in the acute stage;
• patients who have recently suffered from gastric and duodenal ulcers;
• patients with vascular retinopathy;
• patients who have recently suffered intracranial or intracerebral hemorrhage;
• patients with pathology of the blood vessels of the brain or spinal cord;
• patients who have recently undergone surgery on the brain, spinal cord, or eyes;
• patients with a history of bronchiectasis or pulmonary hemorrhage.

Caution should be exercised if the patient is concomitantly receiving medications that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet aggregation inhibitors, or other antithrombotic drugs.
In patients at risk of developing gastric and duodenal ulcers, appropriate preventive treatment can be prescribed.
If there is an unexplained decrease in hemoglobin or blood pressure, it is necessary to look for the source of bleeding.
The safety and effectiveness of Xarelto ® in patients with prosthetic heart valves have not been studied; therefore, there is no data confirming that the use of Xarelto ® 20 mg (15 mg in patients with creatinine clearance 49-15 ml/min) provides a sufficient anticoagulant effect in this patient. categories of patients.
Xarelto ® is not recommended as an alternative to unfractionated heparin in patients with hemodynamically unstable pulmonary embolism or in patients who may require thrombolysis or thrombectomy, since the safety and effectiveness of Xarelto ® in these clinical situations has not been established.
If an invasive procedure or surgery is necessary, Xarelto ® should be discontinued at least 24 hours before the procedure and based on the doctor's opinion.
If the procedure cannot be delayed, the increased risk of bleeding should be weighed against the need for urgent intervention.
Xarelto should be restarted after an invasive procedure or surgery, provided appropriate clinical indicators and adequate hemostasis are present. (see section "Pharmacological properties / Metabolism and excretion").
When performing epidural/spinal anesthesia or spinal puncture in 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 by the use of an indwelling epidural catheter or concomitant therapy with drugs that affect hemostasis. Traumatic epidural or spinal puncture or repeat puncture may also increase the risk.
Patients should be monitored for signs and symptoms of neurological impairment (eg, numbness or weakness of the legs, bowel or bladder dysfunction). If neurological disorders are detected, urgent diagnosis and treatment are necessary.
The physician should weigh the potential benefit against the relative risk before performing spinal surgery in patients receiving anticoagulants or who are scheduled to receive anticoagulants for the purpose of preventing thrombosis. There is no clinical experience with the use of rivaroxaban in dosages of 15 mg and 20 mg in the situations described.
To reduce the potential risk of bleeding associated with concomitant use of rivaroxaban and epidural/spinal anesthesia or spinal puncture, the pharmacokinetic profile of rivaroxaban should be considered. Insertion or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of rivaroxaban is assessed as weak.
However, the exact time to achieve a sufficiently low anticoagulant effect in each patient is unknown.
Based on general pharmacokinetic characteristics, the epidural catheter is removed after at least 2 times the elimination half-life, i.e. no earlier than 18 hours after the last dose of Xarelto ® for young patients and no earlier than 26 hours for older patients. Xarelto ® should be prescribed no earlier than 6 hours after removal of the epidural catheter.
In the event of a traumatic puncture, the administration of Xarelto ® should be postponed for 24 hours.
Safety data obtained from nonclinical studies
With the exception of effects associated with enhanced pharmacological action (bleeding), analysis of preclinical data obtained in pharmacological safety studies did not reveal any specific hazard to humans.

Impact on the ability to drive vehicles/work with moving machinery

Cases of fainting and dizziness have been reported with the use of Xarelto ® (see section "Side effects"). Patients who experience these adverse reactions should not drive vehicles or work with moving machinery.

Release form

Film-coated tablets of 15 mg and 20 mg.
In production at Bayer AG, Germany:
For 15 mg tablets: 14 or 10 tablets in blisters made of Al/PP or Al/PVC-PVDC. 1, 2, 3 or 7 blisters of 14 tablets each or 10 blisters of 10 tablets each along with instructions for use in a cardboard box.
For 20 mg tablets:
In production at Bayer Healthcare Manufacturing S.r.L., Italy:
For 15 mg tablets: 14 or 10 tablets in blisters made of Al/PP or Al/PVC-PVDC. 1, 2 or 7 blisters of 14 tablets each or 10 blisters of 10 tablets each along with instructions for use in a cardboard box.
For 20 mg tablets: 14 or 10 tablets in blisters made of Al/PP or Al/PVC-PVDC. 1, 2 or 7 blisters of 14 tablets each or 10 blisters of 10 tablets each along with instructions for use in a cardboard box.

Storage conditions

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

Best before date

3 years.
Do not use after expiration date.

Conditions for dispensing from pharmacies

On prescription.

Name and address of the legal entity in whose name the registration certificate was issued

Bayer AG, Kaiser-Wilhelm-Allee 1, 51373 Leverkusen, Germany
Bayer AG, Kaiser-Wilhelm-Allee, 1, 51373 Leverkusen, Germany

Manufacturer

Bayer AG, Kaiser-Wilhelm-Allee, 51368 Leverkusen, Germany
Bayer AG, Kaiser-Wilhelm-Allee, 51368 Leverkusen, Germany
or
Bayer Healthcare Manufacturing S.r.L., Via Delle Groane, 126-20024 Garbagnate Milanese (province of Milan), Italy
Bayer HealthCare Manufacturing S.r.L., Via Delle Groane, 126-20024 Garbagnate Milanese (MI), Italy
(for packages No. 14, 28, 98 and 100)

For further information and complaints please contact:
107113 Moscow, 3rd Rybinskaya st., 18, building 2

The direct anticoagulant is Xarelto. Instructions for use prescribe taking tablets of 2.5 mg, 10 mg, 15 mg and 20 mg for vascular pathologies. According to doctors, this drug helps in the treatment of thrombosis, embolism and the prevention of stroke and heart attack.

Release form and composition

The drug Xarelto is available in the form of tablets for oral use, pink, round, convex on both sides with an engraving in the form of a triangle, inside of which the dosage is indicated (number 10). The tablets are packaged in blisters of 5 or 10 pieces in a cardboard box.

The main active ingredient of the drug is micronized Rivaroxaban. Each tablet contains 2.5 mg, 10 mg, 15 mg and 20 mg of the active ingredient.

Indications for use

What does Xarelto help with? Tablets are prescribed for:

• prevention of stroke and systemic thromboembolism in atrial fibrillation of non-valvular origin, and so on;
• prevention of venous thromboembolism after large-scale orthopedic operations in the lower extremities.

Instructions for use

Xarelto is taken orally with meals. If the patient is unable to swallow the tablet whole, it may be crushed and mixed with water or a liquid food such as applesauce immediately before administration.

Take Xarelto 15 or 20 mg tablets immediately before meals. The crushed tablet can be administered through a gastric tube. The position of the probe in the gastrointestinal tract must be additionally agreed with the doctor before taking the medication.

The crushed tablet should be administered 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 any remaining drug from the walls of the tube.

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

The recommended dose is 20 mg once a day. For patients with impaired renal function (Cl creatinine 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

Xarelto therapy should be considered a long-term treatment, continued as long as the benefit of treatment outweighs the risk of possible complications.

What to do if you miss a dose

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.

pharmachologic effect

Xarelto directly inhibits factor Xa and has an anticoagulant effect, which determines the mechanism of action of the drug. The active ingredient of the drug, rivaroxaban, has very high bioavailability when taken orally. Its bioavailability is approximately 80 - 100%.

The drug is very effective, since the most important role in the coagulation cascade is played by the activation of factor X through the external and internal coagulation pathways with the formation of factor Xa. Rivaroxaban is absorbed very quickly. Within 2 to 4 hours after taking the drug, the maximum concentration of the active substance in the blood is reached.

Contraindications

According to the instructions, Xarelto is contraindicated in:

• Liver diseases in which coagulopathy is observed.
• Severe renal failure.
• Hereditary galactose or lactose intolerance.
• Pregnancy and lactation period.
• Intracranial, gastrointestinal or other bleeding.
• Conditions in which there is a high risk of major bleeding.
• Under the age of eighteen.
• Hypersensitivity to the active substance (rivaroxaban) or any other substances contained in the tablets;
• Concomitant treatment with any other anticoagulants.

Side effects

During the course of drug therapy, patients experienced the development of the following side effects:

• Increased bilirubin concentration.
• Increased level of liver transminase activity.
• From the hematopoietic system - the development of iron deficiency anemia, thrombocytopenia.
• From the heart and blood vessels - decreased blood pressure, formation of bruises and hematomas under the skin, in rare cases, tachycardia.
• Hemorrhages in the eyeball are possible.
• Impaired liver function, development of jaundice.
• Peripheral edema.
• Fever.
• Hematuria.
• General weakness, malaise.
• Headaches, fainting, dizziness, hemorrhages in the brain.
• Hemoptysis, frequent nosebleeds.
• Allergic skin reactions - itching, hives, rashes, hemorrhages under the skin.
• From the digestive tract - dyspepsia, flatulence, nausea, dry mouth, bleeding gums, exacerbation of chronic diseases of the digestive canal, risk of gastrointestinal bleeding.

Children, pregnancy and breastfeeding

The drug is contraindicated during pregnancy and breastfeeding. In children, Xarelto is prohibited until the age of 18.

special instructions

Patients with severe renal insufficiency should take Xarelto under the supervision of a physician, since in this case the concentration of the active substance of the drug in the blood plasma increases, and this increases the risk of internal bleeding.

If hemoglobin and blood pressure levels decrease during drug therapy, the cause and probable source of internal bleeding should be looked for.

Antithrombotic drugs, including Xarelto, should be prescribed with caution to patients at high risk of bleeding.

Drug interactions

Taking Xarelto and rifampicin, which is a strong inducer of CYP3A4 and P-gp, leads to a decrease in the pharmacodynamic effects of the drug. Therefore, treatment with this drug with other strong inducers should be carried out with caution.

It has been established that Clarithromycin and may lead to variable changes in rivaroxaban concentrations, but this is considered to be within the order of normal variability and is not clinically significant.

The concomitant use of rivaroxaban and dronedarone should be avoided as there are no clinical data on this combination.

Analogues of the drug Xarelto

For the treatment of thrombosis and embolism, analogues of action can be prescribed:

1. Warfarin Nycomed.
2. Pradaxa.
3. Ukidan.
4. Plagril.
5. Calciparin.
6. Fenilin.
7. Thrombo ACC.
8. Avelizin Brown.
9. Complamin.
10. Angiovitis.
11. Dextran.
12. Urokinase medac.
13. Clexane.
14. Tiklo.
15. Thrombopol.
16. Reopoliglyukin.
17. Heparin.
18. Ralofect.
19. Coplavix.
20. Xanthinol nicotinate.
21. Plidol.
22. Tagren.
23. Parsedyl.
24. Pelentan.
25. Ribasan forte.
26. Pentoxifylline.
27. Colfaritis.
28. Brilinta.
29. Troparin.
30. Karinat.
31. Acetylsalicylic acid.
32. Streptase.
33. Dipyridamole.
34. Laspal.
35. Plavix.
36. Reogluman.
37. Klivarin.
38. Aegitromb.
39. Clopidex.
40. Phlogenzyme.
41. Dethromb.
42. Tsibor.
43. Acenocoumarol.
44. Bufferin.
45. Aspirin Cardio.
46. Godasal.
47. Listab.
48. Fibrinolysin.
49. Agrenox.
50. Aspizol.
51. Tiklid.
52. Actilyse.
53. Sinkumar.
54. Karinat Forte.
55. Zilt.
56. Micristin.

Vacation conditions and price

The average cost of Xarelto (15 mg tablets No. 14) in Moscow is 1,545 rubles. The drug is sold from pharmacies with a doctor's prescription.

Tablets should be kept away from children at a temperature not exceeding 30 degrees. The shelf life is 3 years from the date of manufacture indicated on the packaging. Do not use the drug after the expiration date.

The official medical instructions for use of the manufacturer Xarelto are presented in the photo (click to enlarge):

Xarelto 1

Inside. Xarelto 15 mg and 20 mg should be taken with meals.
If the patient is unable to swallow the tablet whole, the Xarelto tablet may be crushed and mixed with water or a liquid food such as applesauce immediately before administration. After taking the crushed tablet Xarelto 15 mg or 20 mg It is necessary to eat immediately.
A crushed Xarelto tablet can be given through a gastric tube. The position of the probe in the gastrointestinal tract must be further 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 a small amount of water must be introduced in order to wash off any remaining drug from the walls of the tube. After taking crushed Xarelto 15 mg or 20 mg tablets, you must immediately receive enteral nutrition.
Prevention of stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation
The recommended dose is 20 mg once daily.
For patients with impaired renal function (creatinine clearance 49-30 ml/min), the recommended dose is 15 mg once daily.
The recommended maximum daily dose is 20 mg.
Duration of treatment: Xarelto therapy should be considered a long-term treatment, continued as long as the benefit of treatment outweighs the risk of possible complications.

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.
Treatment of DVT and PE and prevention of recurrence of DVT and PE
The recommended starting dose for the treatment of acute DVT or PE is 15 mg twice daily for the first 3 weeks, followed by 20 mg once daily for further treatment and prevention of recurrent DVT and PE.
The maximum daily dose is 30 mg during the first 3 weeks of treatment and 20 mg during further treatment.
The duration of treatment is determined individually after carefully weighing the benefits of treatment against the risk of bleeding. The minimum duration of treatment (at least 3 months) should be based on an assessment regarding reversible risk factors (ie, previous surgery, trauma, period of immobilization). The decision to extend the course of treatment for a longer period is based on an assessment regarding persistent risk factors or in the event of the development of idiopathic DVT or PE.
What to do if you miss a dose
It is important to adhere to the established dosage regimen.
If a dose is missed on the 15 mg twice daily dosing regimen, the patient should immediately take Xarelto to achieve the 30 mg daily dose. Thus, two 15 mg tablets can be taken at one time. The next day, the patient should continue taking the drug regularly in accordance with the recommended regimen.
If a dose is missed on the 20 mg once daily dosing regimen, the patient should immediately take Xarelto and continue taking the drug regularly as recommended the next day.
Selected patient groups
No dose adjustment is required depending on the patient's age (over 65 years), gender, body weight or ethnicity.
Patients with liver dysfunction
Xarelto is contraindicated in patients with liver disease accompanied by coagulopathy, which causes a clinically significant risk of bleeding (see section "Contraindications").
Patients with other liver diseases do not require dosage changes (see section “Pharmacological properties / Pharmacokinetics”).
Available limited clinical data obtained in patients with moderate hepatic impairment (class B according to the Child-Pugh classification) indicate a significant increase in the pharmacological activity of the drug. In patients with severe hepatic impairment (Child-Pugh class C), no clinical data are available.
Patients with impaired renal function
When prescribing Xarelto to patients with renal failure (creatinine clearance 80-50 ml/min), no dose adjustment is required.
For the prevention of stroke and systemic thromboembolism in patients with non-valvular atrial fibrillation with renal failure (creatinine clearance 49-30 ml/min), the recommended dose is 15 mg once daily. When treating DVT and PE and preventing recurrence of DVT and PE in patients with renal failure (creatinine clearance 49-30 ml/min), no dose adjustment is required.
The limited clinical data available demonstrate a significant increase in rivaroxaban concentrations in patients with renal failure (creatinine clearance 29-15 ml/min). To treat this category of patients Xarelto should be used with caution.
Switching from vitamin K antagonists (VKAs) to Xarelto
When preventing stroke and systemic thromboembolism, treatment with VKA should be stopped and treatment with Xarelto should be started when the INR is<3,0.
For DVT and PE, treatment with VKA should be discontinued and treatment with Xarelto should be started at the INR value<2,5.
When switching patients from VKA to Xarelto, after taking Xarelto, INR values ​​will be erroneously high. The INR 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 (VKAs)
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 the INR. Patients switching from Xarelto to a VKA should take a VKA concomitantly until the INR reaches >2.0. During the first two days of the transition period, a standard dose of VKA should be used, followed by a dose of VKA determined depending on the INR value. Thus, during concomitant use of Xarelto and VKA, the 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, the INR value can be reliably determined 24 hours after the last dose.
Switching from parenteral anticoagulants to Xarelto
In patients receiving parenteral anticoagulants, 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.
Cardioversion for the prevention of stroke and systemic thromboembolism
Treatment with Xarelto may be initiated or continued in patients who may require cardioversion. For transesophageal echocardiography (TEE)-guided cardioversion in patients who have not previously received anticoagulation therapy, Xarelto® treatment should begin at least 4 hours before cardioversion to ensure adequate anticoagulation.

The drug seems to be working)

Grade: 5

At 5 weeks of pregnancy, my fetus froze. During hospitalization, I complained to the doctor about pain in my leg and after an ultrasound scan I was diagnosed with non-occlusive deep vein thrombosis. After completing the gynecological questions, I was admitted to the vascular surgery department and there I became acquainted with Xarelto. In the hospital I took 15 mg twice a day. And when I came out, I was embarrassed when I saw the price of the drug, but health is more valuable than any money! In general, the result is as follows: After a month of taking 15 mg twice a day, the dynamics are wonderful. Ultrasound showed that 1 of the three affected veins had cleared and was completely patent. Now I’ve been taking 20 mg once a day for a month and, to be honest, I’ve started to feel my leg again, which worries me very much. Throbbing pain appears from time to time. I plan to go for an ultrasound scan in a couple of weeks, but I think everything is fine. In general, there are no side effects (to avoid stomach problems I take omeprazole), I also take Phlebodia 600 at the same time and always wear class 2 compression stockings. Thanks to the scientists for such a wonderful drug! I don’t want to switch to analogues, because I don’t want to risk my health and treatment time for the sake of dubious savings of a couple of thousand rubles.

Grade: 4

I have been taking it for more than a year as a stroke prevention (I had one 3 years ago). There are no negative impressions, it is easy to take, there was no recurrent stroke. BUT...in the blood test, anemia began to be consistently recorded, which was not there before and the cause of which cannot be determined:-(
It’s a pity that the effectiveness cannot be monitored objectively; INR is not used)

Grade: 4

As I understand it, this is the most modern drug that prevents the formation of blood clots. It works great! I had blood clots all over my leg, and now there is only one left. There is a positive forecast that he too will disappear.
I liked that there were no side effects or allergies to the medicine. The main thing is not to exceed the dose - the medicine is serious and you should always consult a doctor. I drink it at the same time in the morning and feel great. INR control is not needed, the drug acts gently and constantly. Somehow I missed an appointment, felt weak and dizzy. As I understand it, most likely I will have to drink it for life. The drug is expensive, but the price is justified.

Grade: 4

Previously, I took another drug, but after two operations, the doctor prescribed Xarelto.
Unfortunately, it is prescribed for an indefinite period (but the instructions, by the way, indicate that it is recommended to take it for no more than one year; if there is no effect, you should stop taking it). I've been taking it for about six months at the moment. At the recommended dose of 20 mg per day, I take a little more than a tablet (the pack contains a dosage of 20 mg). The result is about 25 mg of medication per day. Since I have difficulty swallowing, I crush the medicine into food (they can also be taken this way, the doctor said there is no difference).
Due to the increased dosage, the first 3 weeks there was dry mouth. Over time, everything passed. To this day, the blood clot is not resolving, but at least it is not growing any further. There are also no new blood clots (they appeared before, but now there have been none for six months). The drug seems to have an effect. But for its price the effect is still not good enough, but there are no analogues

Grade: 5

In addition, I am at risk of stroke and suffer from kidney failure. According to the instructions, I take 15 mg once a day. And with this dosage, the drug, it seems to me, works. I have been taking it for 5-6 months, no stroke has occurred.

Grade: 5

I had deep vein thrombosis. There was swelling in the lower leg, and the temperature even increased. They prescribed Xarelto and bought it, although the drug is not cheap. I took 15 mg twice a day before meals for the first 2-3 weeks, and then switched to 20 mg once a day.
I have been undergoing treatment for about 3 months. The pain and heaviness gradually go away. Vascular ultrasound shows improvement.

Grade: 5

Grade: 5

I have a lot of thrombotic masses on my legs. The doctor prescribed Xarelto. The summary for it is very detailed; the side effects included bleeding. I doubted whether it was worth taking the drug, since it had such possible unwanted reactions. Still, I decided, which I don’t regret at all now.
Before starting the course, it is necessary to examine the stomach (FGDS) to find out if there are any ulcers inside. And only if everything is clean, then taking the drug is allowed.

The dosage regimen is interesting, with increasing dosage. I took 10 mg for 20 days, and 20 mg for 40 days. Surprisingly, there were no side effects. Additionally, I drank herbal infusions and omeprazole to protect my stomach.
After a course of Xarelto, I did a venous doppler. The blood clots have resolved, the patency is excellent! Moreover, very quickly - in just 2 months. Xarelto is my salvation. Even if it is expensive, even if it is not sold everywhere, it gives a wonderful result.
We are all individuals, our bodies react differently to new medications, so it is advisable to consult with doctors very carefully and not neglect additional research. Then the result will be excellent!

Grade: 5

My mother took Xarelto. The doctors prescribed Warfarin, but the dosage and the effect itself are very strong, so they decided not to risk it. Although the drug is cheaper than Xarelto.

Tablets cost about 3,000 rubles for 28 pieces of 20 mg each (you can rarely find them cheaper). Now we’ve decided to buy in large batches at once, so at least we can save some money.
Mom has been taking it for six months, and all blood tests are more or less good. If previously a bruise appeared at the slightest pressure on the skin, now we don’t have such problems. The tablets have no side effects.
In our case, the drug must be taken for life. Both due to age and health status.
Excellent product, easy to use. And most importantly, it works as it should, the results are visible both externally and by analysis. We don’t regret switching to Xarelto, so far the medicine has been nothing but good.

Grade: 5

About a year ago I was diagnosed with a condition that requires me to take anticoagulants regularly. At first Warfain was prescribed. I started taking it, but on the third day bleeding began with an exorbitant increase in INR. Warfain was immediately discontinued and Xarelto was prescribed, but they warned me that the drug was “slightly” more expensive and that I should not worry. In fact, this “slightly” turned out to be 20 times more expensive. The amounts are simply shocking. As the doctor said, there are simply no analogues with a similar composition. The drug is young and we can’t expect analogues in the next couple of years. If you buy a large package of 100 tablets, you can save a couple of thousand every three to four months. At least some savings. Over the year, the cost of the drug has increased by about 90 rubles, which seems a little, since the state controls the prices for the list of necessary drugs, and Xarelto is one of them, prices should not fluctuate depending on the exchange rate. That's a plus.

The main drawback is the duration of the course of treatment, since I drank one month out of three. There is no point in writing about the results. But the thrombus has become softer and the boundaries seem to have begun to blur, its diameter has decreased, but there is still pain. Still take it for 2 months, and then we can talk about whether it works or not. But the positive dynamics give us hope.
For the first month I took 15 mg per day, now I increase the dosage to 20. Now the intake has become much more convenient - a whole tablet. Previously, you had to divide it in half, and then “saw off” another quarter from the half, so that the total would be three quarters. This is not entirely convenient, it’s a pity that the manufacturer did not think about producing tablets in a dosage of 15 mg for ease of use in the first month.
I don’t deviate from the instructions. The list of side effects and contraindications is small, I was not affected by unpleasant symptoms in the form of nausea or weakness, my blood pressure was also normal.

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Blood clots can cause a variety of health problems, even fatal in some cases. To prevent the development of diseases associated with increased blood clotting, medications are taken that reduce clotting. A group of drugs that reduce blood clots is quite widely represented on the pharmaceutical market. One of the latest developments is the drug Xarelto.

Composition and release form

Xarelto is only available in tablet form. Xarelto tablets are coated with a special film-like coating, pink-brown or red-brown in color.

The main substance in the tablet is rivaroxaban, which can be 10, 15 or 20 mg per tablet. The excipients of the tablet itself are standard:

• lactose monohydrate;
• cellulose;
• magnesium stearate and others.

The film consists of titanium dioxide, macrogol, hypromellose and dye, due to which it dissolves well when exposed to suitable conditions.

Manufacturer

Xarelto is an original medicine, it is produced by Bayer AG, which is located in Germany. However, this manufacturer also has a representative office in Russia, so if you have any questions, you can contact them there.

Indications for use

The drug is used to weaken overly active thrombus formation processes in the body. It is used as a prophylactic agent, usually in combination with other measures to reduce blood clots. Since the medication acts on the blood clot formation system, it is used to combat thromboembolism during operations on both the lower extremities and during interventions in orthopedics.

Xarelto is also indicated for patients with thrombosis of deep veins and arteries. In this case, it also prevents thromboembolism.

Schematic view of thrombus formation in blood vessels

Separately, we should highlight the condition of atrial fibrillation, in which Xarelto also showed excellent results.

A detailed description of the indications for use of the drug can be found in the Vidal reference book of medications.

Contraindications

The list of contraindications for these tablets is quite extensive and is divided into general and dose-dependent contraindications.

General contraindications:

• Lactation and pregnancy.
• Childhood.
• Any hypersensitivity to components, including allergic reactions.
• Diseases that can contribute to bleeding: aneurysm or surgical interventions.
• Disorders of the excretory system, chronic renal and liver failure.
• It is prohibited to prescribe the medicine together with other drugs of the same effect in order to avoid the development of bleeding and bleeding disorders. But there are exceptions: the process of switching to Xarelto after treatment with other drugs from the anticoagulant group.
• Injuries or other injuries that lead to extensive bleeding; such conditions may include peptic ulcers of the stomach or intestines.

But in addition to this, there are also conditions that are contraindications only during the period of use of the medication at a certain dose: taking a dosage of 10 mg can sometimes affect the condition after surgery on the femur.

In addition, in addition to clear contraindications for use, there is also a list of conditions for which the drug is indicated under the close supervision of the attending physician.

• Combined use with drugs that are associated with effects on hemostasis.
• Severe renal impairment, including renal failure. Most often, this leads to signs of overdose and impaired kidney function.
• When carrying out therapy with antiviral drugs against HIV, as well as antifungal drugs.
• If the patient has a congenital tendency to exhibit bleeding.
• The medication is also dangerous if you have had a stomach ulcer.

If undesirable effects occur, the doctor may stop Xarelto and prescribe another drug of a similar group, for example, which is closest to the drug in action. Only the attending physician can make a choice, Eliquis or Xarelto, and only if necessary, if the latter has already been taken. The difference between the drugs is that Xarelto has been better studied, since it was released on the market earlier than Eliquis and managed to go through quite a lot of tests.

Instructions for use

The medication should be taken orally. It is advisable to take it directly with food; in some cases it is permissible to crush the tablet to give it with food. Splitting the tablet is also allowed. However, if it is not possible to take it during meals, then you can take the drug at other times. But remember that if in the case of a dosage of 10 mg the medication does not cause significant harm, then it is still advisable to tie higher dosages precisely to the time of eating.

The most common regimen is 10 mg per day. You need to take Xarelto for a long time, not like some other groups of drugs, but also for quite a long time.

Important! On average, the treatment period can range from 3 weeks to 5.

After surgery, Xarelto should be taken as quickly as possible, the best option being six or ten hours after the procedure.

It is not recommended to skip treatment. If the patient has forgotten to take the pill, he should take it immediately as soon as he remembers. After this, you will need to return to the prescribed treatment regimen. It is strictly forbidden to double doses to compensate for a missed dose.

Overdose

Although the idea of ​​bleeding from an overdose of Xarelto seems logical, such cases have not yet been reported. This is due, first of all, to the fact that upon reaching a certain level of concentration in the blood, the drug simply stops being absorbed, remaining in the body in the form of a “concentration plateau”.

Activated carbon. first aid for drug overdose

Regular activated carbon works best in case of overdose. The patient should be taken to the hospital only in extreme cases that threaten life and health. Hemodialysis has absolutely no effect on the patient's condition, so hospitalization is usually not indicated.

Therefore, in case of poisoning, it is best to carry out symptomatic treatment, stopping the symptoms that arise and alleviating the person’s condition in all possible ways.

special instructions

In addition to situations in which special caution must be exercised in prescribing, there are other special instructions when taking the drug.

Doctor's opinion:

“First of all, those who take Xarelto should know that treatment requires monitoring of the blood clotting system. This is especially true for elderly patients who may develop bleeding. If this happens, the elderly patient needs to adjust the dose. However, younger people should also regularly monitor the functioning of the blood clot system in order to identify possible problems as early as possible.”

If the patient is prescribed any surgical intervention, the use of the drug must be discontinued. This is done no less than a day before the operation takes place. Therefore, it is important to tell your doctor that you are taking a blood clotting medication before scheduling surgery.

Xarelto does not affect the ability to drive, but in some isolated cases, patients have experienced general malaise or decreased alertness while taking it. Therefore, if it is necessary to combine medication with driving, the patient should exercise maximum caution.

If, when monitoring your blood condition during an appointment, a sharp drop in hemoglobin values ​​was detected, as well as a serious drop in blood pressure, this may mean that internal bleeding is likely to occur. In this case, it is necessary to take the person to the hospital and look for the source, as well as the cause of the appearance.

Xarelto and alcohol

The combination of Xarelto and alcoholic beverages is one of the most popular problems that worries many patients. If you pay attention to the instructions for use of most medications, you will find that none of them can be combined with alcoholic beverages. However, there are also drugs with special contraindications for this combination. Xarelto can perhaps be called such a medicine. Alcohol, in addition to its negative effects on the heart muscle, also seriously contributes to thicker blood. This is exactly the opposite of the effect of the drug.

Important! Thus, by drinking alcohol, you can neutralize the effect of the pill and reduce the treatment to zero.

However, simply skipping a dose is also not recommended. Anticoagulants are drugs that require regular use; skipping a dose due to alcohol is absolutely unacceptable. Therefore, when the choice arises between treatment and drinking alcohol, it would be better to choose therapy.

During pregnancy and lactation

Pregnancy and breastfeeding are clear contraindications for taking Xarelto. Studies have shown that the medication negatively affects the body of a woman and baby. Studies of the effect of the drug, both on the body of pregnant women and on the body of lactating women, were carried out on animals, and as a result, a negative effect of the drug was revealed, both in the first and in the second case.

During pregnancy, rivaroxaban is able to cross the placental barrier and enter the fetus, which, in turn, can cause bleeding. Bleeding also occurs in the expectant mother. Therefore, use is only possible in combination with contraception for all women of fertile age.

During lactation, the substance is actively excreted in breast milk and can thus enter the baby’s body during feeding. You can start taking the drug only if the lactation period is completed, or if the child is not fed breast milk during this period.

Cancellation and switching to other drugs

The drug is discontinued by gradually reducing the dosage over a short period of time.

Doctor's opinion: “Switching to other medications should be done with caution, since in some cases the anticoagulation effect may decrease at the very beginning of such a transition. In this case, it is necessary to compensate for the insufficient concentration of anticoagulants in the blood with the help of other medications. This is the only situation in which the combination of Xarelto and any other drugs from its group is allowed.”

The transition scheme looks quite simple: the patient cancels the dose and uses a new drug at the time when he should have taken the medicine the next time. This ensures smoothness during the transition period and allows you not to pause in treatment or reduce the therapeutic effect of it.

Diet upon admission

List of products included in diet number 10

When taking anticoagulants, the patient simply needs to follow a diet. This is due, first of all, to the fact that the blood clotting system is highly dependent on the intake of many substances into the body, including vitamins (vitamin K) and some minerals. In addition, the diet helps improve vascular health, which also directly affects the formation of blood clots in them. The healthier the vessels, the lower the likelihood of thromboembolism occurring in them.

Table 10 is suitable as a diet when taking medication:

1. Refrain from taking animal fats and switch to vegetable fats.
2. Products of animal origin are allowed to be eaten only with a reduced fat content, including dairy and fermented milk products.
3. It is recommended to increase the amount of cereals in the diet.
4. Protein can be obtained from lean meat, for example, poultry or rabbit, as well as certain lean varieties of fish.

You should also pay attention to greens, vegetables and fruits. Reduce your intake of chocolate and, in general, foods containing cocoa or cocoa butter.

Price and rules for dispensing from pharmacies

Xarelto is only available with a doctor's prescription.

The cost of packaging the drug is quite high and fluctuates around 1,500 rubles. This is an average price and may vary among different pharmacy chains. However, the drug is quite expensive and many patients may not be able to take it precisely because of the price. This should be taken into account when prescribing, since medications should not be changed too often.

Table of current prices for the drug Xarelto in online pharmacies. The last data update was 03/29/2020 00:00.