Find a cheap domestic drug similar to Xarelto. Regimen and dosage regimens. Visitor survey results

Xarelto (Bayer, Germany) belongs to the group of anticoagulants direct action. The active component of the product is rivaroxaban. It should be noted that there is no exact cheaper analogue of Xarelto with the same component in the composition, but there are medications that are similar in their mechanism of action and therapeutic effect.

The medicine reduces thrombin activity and the likelihood of recurrent blood clots, and restores blood fluidity. Prescribed for the prevention of venous thrombosis of the lower extremities.The product has a high cost.

• Tablets 20 mg, 100 pcs. - 8890 rubles, 15 mg, 100 pcs. - 8950 rub.

List of cheaper analogues of Xarelto

The drugs included in this list belong to the new generation of anticoagulants. These are the most accurate analogues of Xarelto in terms of the mechanism of action (blocks thrombin directly), although the main active components of the medications differ from it.

1. Eliquis (Bristol-Myers, USA). The main component is apixaban. Affects blood clotting. Used as a prophylactic agent to prevent postoperative complications in the hip or knee joint, and also to reduce the risk of stroke.

• Price of tablets 2.5 mg, or 5 mg 20 pcs. - 887 rub., 2.5 or 5 mg 60 pieces - 2450 rub.

2. Pradaxa (Boehringer Ingelheim, Austria). Active ingredient dabigatran etexilate has anti-clotting properties. The main effect is associated with inhibition of thrombin.

Appointed as preventive measures for cardiac and venous diseases associated with the risk of thrombosis. The medication is one of the best cheaper analogues of Xarelto with different shapes release according to the concentration of the substance.

• The cost of capsules is 75; 110 or 150 mg, 30 pcs. the price is almost the same 1815 - 1900 rubles.

Direct acting low molecular weight heparin analogues

Medicines in this group are distinguished by high bioavailability. Their biological qualities are more stable. Medicines have a suppressive effect on thrombin. They have a positive effect on blood fluidity, as well as blood supply to organs and tissues.

1. Fragmin (Pfizer, USA). Active ingredientdalteparin sodium. Indications for use: heart diseases - angina pectoris, myocardial infarction, acute deep vein thrombosis. Indicated for patients with chronic renal failure and as a preventive measure aimed at changing the quality of blood clotting during hemofiltration. Available in the form of a solution for intravenous injections.

• Packaging cost 5000 0.2 ml 10 pieces - 2400 rub.

2. Clexane (Sanofi-Aventis, France). Active ingredient enoxaparin sodium. Prescribed as part of complex therapy for the prevention of reducing the risk of blood clots against the background acute form therapeutic diseases, in orthopedic practice and general surgery, as well as during hemodialysis.

• Syringes 20 mg; 0.2 ml, 10 pcs. - 1680 rub., 0.4 ml each - 2830 rub.

3. Wessel Due F (Alfa Wassermann, Italy). Main component sulodexide. Natural preparation- produced from the intestinal lining of animals. The medication is prescribed for angiopathy with a predisposition to the formation of blood clots, damage to peripheral arteries due to atherosclerosis and diabetes, and cerebrovascular dysfunction.

• Cost of caps. 250 units 50 pieces - 2300 rubles. Also available in the form of a solution for injections.

Indirect anticoagulants

1. Warfarin (Grindeks, Russia). Active ingredient warfarin. Most popular in medical practice more cheap analogue xarelto. The action of the medication is associated with the process of slowing down blood clotting.

Indications for use include: prevention of pulmonary embolism, thrombosis in the inferior vena cava system, reducing the risk of blood clots after surgery, stroke and ischemic attacks.

• Price per pack of 2.5 mg tablets, 100 pcs. - 170 rub., 100 pieces 3 mg - 156 rub., 5 mg 100 pieces. - 200 rub.

2. Varfarex (Grindeks, Latvia). Active substance warfarin. Anticoagulant suitable for long term treatment. Prevents the possibility of blood clots and inhibits the growth of existing ones. The drug is indicated for thrombosis, as well as heart diseases - heart attack, ischemic stroke, during operations related to the replacement of heart valves.

• Pack price tab. 5 mg, 100 pieces - 200 rubles, 3 mg - 150 rubles.

3. Fenilin (Health of Russia). Active ingredient phenindione has an anticoagulant effect. Area of ​​application - preventive measures and prevention of embolism, reducing the risk of blood clots after surgery.

• Cost of tab. 30 mg, 20 pcs. - 185 rub.

P.S. The drugs included in the list of cheap analogues of Xarelto have a list of serious contraindications and side effects. Replacement with more inexpensive analogue determined by the doctor.

Despite the similarity of drugs in their mechanism of action, each of them has individual characteristics. The correct choice is determined by a specialist depending on the current disease and the overall clinical picture.

In modern orthopedics, the drug Xarelto is widely used - instructions for use; patients and doctors indicate its anticoagulant effectiveness in bone fractures and extensive surgical interventions. The drug helps eliminate and prevent complications manifested by vascular thrombosis, pulmonary and systemic thromboembolism.

Xarelto tablets

A medicine intended for the treatment and prevention of thrombosis, thromboembolism, myocardial infarction. The medicine is produced by the German pharmaceutical company Bayer. Tablets are prescribed by a doctor after necessary tests, excluding the presence of contraindications. If the instructions for use are not followed, the medicine may be harmful to health.

Composition and release form of the drug

Xarelto is sold in pharmacies in tablet form. The pills have a round, biconvex shape, covered with a film coating. The tablets are colored red-brown, their surface is engraved with the manufacturer's company and dosage. According to the instructions, the pills have the composition indicated in the table:

Pharmacological properties

According to the instructions, the drug is a direct-acting anticoagulant. The medicine helps suppress platelet activation. This pharmacological action helps in the treatment and prevention of thrombosis. The product is highly bioavailable, has a rapid effect and a predictable dose-dependent response. The substances included in the composition are excreted by the liver.

Indications for use of Xarelto

The drug is prescribed by doctors after the patient has completed the necessary diagnostic studies. Instructions for use include the following readings:

• prevention of myocardial infarction, stroke and thromboembolism in patients with non-valvular atrial fibrillation;
• treatment of deep vein thrombosis, pulmonary embolism;
• prevention of thrombosis;
• the need for preventive measures to prevent venous thromboembolism in patients undergoing operations on lower limbs.

Directions for use and dosage

The instructions prescribe taking the product orally, 1 tablet twice a day. The course of treatment is 1 year. If necessary, therapy can be extended for another 12 months. If for some reason a dose was missed, the instructions recommend that you immediately take the tablet, then continue using it as usual. You can swallow the pills regardless of meals.

special instructions

Caution should be exercised when prescribing the drug when the patient is being treated with drugs that affect hemostasis (platelet aggregation inhibitors, other antithrombotic drugs). Patients who have had acute coronary syndrome taking Xarelto with acetylsalicylic acid, can take non-steroidal anti-inflammatory drugs if their use justifies the risk of bleeding.

Patients with the possibility of ulcerative lesions of the gastrointestinal tract are allowed to use appropriate preventive measures. If there is a decrease in performance blood pressure or there is a drop in hemoglobin levels in laboratory analysis blood, specialists must detect the source of bleeding.

When performing spinal or epidural anesthesia or spinal puncture in patients receiving platelet aggregation inhibitors for the prevention of thromboembolism, there is a risk of hematoma. This phenomenon can cause paralysis. The possibility of complications increases when using a permanent epidural catheter and therapy with drugs that affect hemostasis. To reduce the risk of bleeding, it is better to perform a puncture when rivaroxaban has weak anticoagulant activity.

Xarelto should be stopped 12 hours before surgery or an invasive procedure. There have been cases of fainting and severe dizziness against the background of medication use. This factor can significantly affect the ability to control transport and work with complex mechanisms. If such reactions were noted, patients are prohibited from driving or manipulating devices that require increased attention.

During pregnancy

Studies related to the safety and effectiveness of Xarelto during pregnancy were conducted in animals. As a result, the toxic effects of rivaroxaban on the body of the expectant mother and child were revealed. The medicine is contraindicated during pregnancy due to the high risk of penetration of the active substance through the placenta and the possibility of bleeding. Women who are in childbearing age The medication is allowed only when using contraception.

The results of animal studies of the possibility of taking Xarelto during breastfeeding showed that the active substance is excreted in milk. Experiments have proven that during feeding, toxic substances can enter the child’s body. It is allowed to start taking Xarelto only after the end of the lactation period.

For impaired renal and liver function

The instructions for use of Xarelto say that taking the drug is contraindicated for people suffering from severe renal failure with creatine clearance less than 15 ml/min. There are no clinical studies. The medicine is prescribed with caution to patients with a severe form of the disease with a CC of 30-15 ml/min. Under the supervision of a physician, the drug is used in the treatment of patients with moderate severity kidney failure, who simultaneously take medications that increase the concentration of rivaroxaban in the blood plasma.

The use of Xarelto is contraindicated in patients with liver disease that occurs with coagulopathy. Prescription may lead to bleeding. The pharmacological activity of the drug may increase in people suffering from moderate organ dysfunction. The presence of other liver diseases in patients taking Xarelto does not require adjustment of the required dose.

Drug interactions

The active substance Xarelto is not an inhibitor and does not induce isoenzymes related to the main isoforms of cytochrome. The drug is not recommended for use simultaneously with systemic therapy with drugs from the azole group. Such medications are powerful inhibitors of the CYP3A4 isoenzyme and P-glycoprotein. They can multiply pharmacological effects Xarelto. Concomitant use with rifampicin, carbamazepine, phenobarbital reduces the effectiveness of rivaroxaban.

Caution should be exercised when using the drug with parenteral anticoagulants, as such interaction may cause bleeding. A similar effect is observed when the drug is combined with non-steroidal anti-inflammatory drugs. The combined use of tablets with 500 mg of acetylsalicylic acid did not reveal a clinically significant interaction. There are no data on combination with dronedarone.

Xarelto and alcohol

Clinical studies have been conducted on the compatibility of Xarelto and alcohol. As a result, it turned out that using the drug together with alcoholic beverages can lead to a number of undesirable consequences, provoke side effects and bleeding. The instructions for use of Xarelto say that this drug should not be taken with alcohol.

Side effects

The pharmacological action of Xarelto may increase the risk of bleeding. The likelihood of occurrence is especially high in patients suffering from severe arterial hypertension or being treated with drugs that affect hemostasis. The source of bleeding can be any organs and tissues. The consequences of this negative reaction of the body are the formation of anemia.

Complications of a hemorrhagic nature can manifest as weakness, swelling unknown etiology, pallor skin, dizziness, headache, shock of unknown origin, shortness of breath. Due to anemia, pain may occur in the chest, angina pectoris, which are signs of myocardial ischemia. Against the background of bleeding, cases of renal failure and interfascial space syndrome were recorded.

There are others side effects from taking the drug Xarelto - instructions for use indicate the following consequences:

• From the cardiovascular and hematopoietic systems, hematomas, thrombocythemia, anemia, tachycardia, and a pronounced decrease in blood pressure may occur.
• The skin reacts with the appearance of a rash, itching, urticaria, hemorrhages, and ecchymosis.
• The effect on the immune system manifests itself in the form of allergic dermatitis and other reactions.
• Adverse reactions of the digestive system: bleeding gums, pain in the gastrointestinal tract, feeling of dryness in the oral cavity, diarrhea, constipation, nausea and vomiting, dyspeptic symptoms.
• From the outside respiratory system Maybe nose bleed, hemoptysis.
• The reaction of the organs of vision manifests itself in the form of hemorrhage in the eye.
• Jaundice may develop and liver failure may occur.
• From the musculoskeletal system: pain in the limbs, hemorrhage in the muscles, deterioration of their tone, hemarthrosis.

Overdose

Uncontrolled use of Xarelto may cause bleeding. To cope with the consequences of an overdose and reduce the absorption of rivaroxaban, you need to drink Activated carbon. To establish control of bleeding, surgical hemostasis, mechanical compression, infusion therapy are performed, red blood cells, fresh frozen plasma, and platelet preparations are used.

There are no studies regarding the effectiveness of aminocaproic acid. If treatment does not produce results, specific procoagulant agents are used. There is limited experience with the use of tranexamic acid in overdose with Xarelto. There are no studies regarding the advisability of using Desmopressin.

Contraindications

The drug can provoke negative changes in the body. Some categories of patients are prohibited from using the medicine Xarelto - the attached instructions for use provide the following contraindications:

• allergic reactions to rivaroxaban or auxiliary components of the medication;
• the presence of active bleeding of clinical significance (intracranial, gastrointestinal);
• liver diseases that occur with coagulopathy (cirrhosis, functional disorders organ);
• therapy with other drugs that have an anticoagulant effect (Warfarin, Enoxaparin, Apixaban);
• severe renal failure;
• treatment of patients who have suffered a transient ischemic attack or stroke with antiplatelet agents;
• pregnancy and lactation;
• age under 18 years;
• lactose intolerance, congenital lactase deficiency.

There are several conditions under which the drug is prescribed under the supervision of a specialist. Xarelto should be taken with caution if the following factors are present:

• increased risk of bleeding;
• severe injuries ah, wounds;
• medium degree renal failure;
• treatment with drugs that affect hemostasis;
• systemic antifungal therapy with agents belonging to the azoles group;
• treatment with HIV protease inhibitors.

Terms of sale and storage

You can buy Xarelto only with a doctor's prescription. The shelf life of the drug is 3 years. So that the medicine retains its therapeutic properties, it must be stored at a temperature not exceeding 30 degrees. The medication should be kept out of the reach of children.

Analogue of Xarelto

The drug has several analogues that are similar in pharmacological action. Before changing your medication, consult your doctor. Popular analogues of Xarelto are:

• Clexane is a direct anticoagulant, low molecular weight heparin. Dispensed in the form of a solution for injection. The drug is intended for the treatment and prevention of thrombosis, thromboembolism, and myocardial infarction. Prescribed with caution if available open wounds and severe injuries.
• Pradaxa is a drug that has anticoagulant and antithrombic effects. Used in orthopedics during recovery after surgery, if there were no extensive injuries with a risk of bleeding. Available in capsule form.

Xarelto price

You can purchase the medicine in pharmacies or order it from online stores. The cost of medicine at different retail outlets can be compared using the table:

Video

Xarelto is an effective drug that belongs to the category of anticoagulants. It is used to prevent the formation of blood clots and prevent thromboembolic complications. The medicine helps reduce the incidence of deaths from blood vessel blockages and strokes. Despite the high effectiveness of the product, sometimes it is necessary to choose cheaper analogues of Xarelto.

Description of the drug

Xarelto is produced in the form of film-coated tablets. Each of them contains an active component - micronized rivaroxaban. The medicine also includes additional components.

The substance belongs to the category of anticoagulants. The active component affects blood clotting. During the period of therapy, it is possible to reduce the activity of thrombin and reduce the risk of recurrent blood clots. The product also restores blood fluidity. The medicine is prescribed to prevent thrombosis of the veins of the legs.

The substance has a fairly high cost. So, 100 tablets with a dosage of 20 mg will cost approximately 8,900 rubles. Therefore, many people have a fair question about what to replace Xarelto with.

Review of cheap analogues of Xarelto

There are quite a few drugs that have similar properties, but are much cheaper:

Warfarin or Xarelto – which is better?

Warfarin is produced in tablet form. The active component of the substance is warfarin sodium. This drug belongs to the category of anticoagulants. It is actively prescribed for thrombosis of veins and arteries, myocardial infarction, pulmonary thromboembolism.

The medicine must be taken orally once a day. This should be done at the same time. Side effects of the substance include hives, risk of bleeding, and abdominal pain.

Limitations include bleeding or a tendency to occur, severe forms kidney and liver failure, diabetes. Relapse should also be considered prohibited. peptic ulcer, chronic form alcoholism, pregnancy, hypertension, stroke.

Xarelto or Eliquis – which is better?

Eliquis has the same indications, contraindications and side effects as Xarelto. However, it is characterized by a lower cost. Thus, a package of Eliquis with a dosage of 5 mg, including 60 tablets, will cost 2,550 rubles. The recommended volume for thrombosis is 10 mg. IN for preventive purposes Eliquis 5 mg is prescribed.

The dose can be adjusted by the doctor. This is done depending on the weight, age category and gender. The concentration of the substance in the blood of elderly patients is 30% higher. The same figure is 18% higher in women. For people who weigh more than 120 kg, the volume of medication needs to be increased.

Which is better Pradaxa or Xarelto?

The medicine Pradaxa is considered an excellent substitute xarelto. This substance is a thrombin inhibitor and is prescribed to people as a direct anticoagulant. The substance contains dabigatran etexilate. It provides thrombin inhibition and prevents thrombosis.

Pradaxa is used to prevent thromboembolism and strokes. The substance is a cheaper alternative to Xarelto. However, it can be prescribed exclusively to adult patients. However, only a doctor can prescribe a substitute. He also determines the treatment regimen. The drug can be taken regardless of food.

Like other analogues of Xarelto, Pradaxa can provoke the following adverse reactions:

This medicine should not be prescribed to older people. It is also not prescribed to patients who are underweight. Pradaxa should not be used if liver or kidney function is impaired. Limitations also include a tendency to hemorrhagic diathesis. For fresh injuries, the medicine is prescribed with great caution. It is prohibited from being prescribed to patients under 18 years of age.

Xarelto or Agrenox

Agrenox is produced in the form of capsules. Its active components are dipyridamole and acetylsalicylic acid. The substance belongs to the category of antiplatelet agents and is actively used to combat pathologies that are accompanied by increased formation of blood clots.

The medicine is prescribed orally, 1 capsule. The product should be taken 2 times a day and washed down with water. It is worth considering that the substance can lead to the appearance side effects. These include a decrease in the content of red blood cells and platelets in the blood, decreased blood pressure and bleeding.

This medicine may not always be taken. Key contraindications include ulcerative lesions of the stomach and duodenum, the formation of nasal polyps, and hemophilia. Also, the drug is not prescribed in the presence of kidney or heart failure at the stage of decompensation.

Xarelto or phenyline

With the help of phenyline, it is possible to suppress the rate of prothrombin biosynthesis. Thanks to the use of the substance, blood clotting is reduced after 8 hours. Maximum action comes in a day. It is worth considering that the medicine has fewer side effects. However, sometimes it causes diarrhea, anemia, fever, and headaches.

Bleeding as a result of using the drug occurs very rarely. The anticoagulant should be taken according to the schedule. The dosage should be selected by a specialist. During therapy, it is necessary to conduct studies of the prothrombin index.

For prevention, 0.03 g of phenyline is prescribed 1-2 times a day. For 20 tablets you will have to pay approximately 175 rubles. Thus, phenyline is a more affordable alternative to Xarelto if a long-term reduction in hemocoagulation is required.

Xarelto or ticlopidine

Thanks to the use of ticlopidine, it is possible to reduce the volume of factor IV and achieve inhibition of platelet aggregation. The result is achieved 2 days after the start of use.

The medicine can be used for cerebral circulatory disorders and atherosclerosis. It can also be used for preventive purposes when there is a threat of thrombosis and stroke. To achieve the desired results and avoid side effects, it is imperative to monitor the coagulation state.

Ticlopidine may cause minor adverse reactions. They manifest themselves in the form of bloating, dizziness and nausea.

The product should not be used in case of bleeding, presence hemorrhagic diathesis, ulcerative lesions of the digestive organs. Contraindications also include pregnancy and lactation.

Xarelto or Syncumar

Sinkumar is actively used for the prevention and treatment of thrombosis, thrombophlebitis, and embolic lesions. The dosage is selected depending on the indications. The prothrombin index parameter is also important. The effect is achieved 2-4 days after the start of therapy.

Treatment should be carried out under the control of the prothrombin index and urine tests for hematuria. The drug has the same contraindications and indications as warfarin. Many patients note that the drug is well tolerated and causes almost no side effects.

Xarelto or heparin

Heparin is produced in the form of a solution for injection. Its active ingredient is sodium heparin. The drug belongs to the category of anticoagulants and is actively used for thrombosis. It is also used for pulmonary thromboembolism and unstable angina.

The drug reduces the risk of developing acute thrombosis and heart attack. For this purpose, it is administered intravenously or intramuscularly. TO adverse reactions include reversible alopecia, relapse of asthma, osteoporosis, bleeding. They usually occur with prolonged use of the product.

The drug should not be used for bleeding, hemophilia, ulcers, cirrhosis, tuberculosis. Limitations also include hemorrhagic stroke, pregnancy and lactation.

Xarelto or cardiomagnyl

Cardiomagnyl belongs to the category of antiplatelet agents and is included in the group of non-steroidal anti-inflammatory drugs. The main component of the substance is acetylsalicylic acid. It copes with pain, reduces temperature indicators and prevents platelet aggregation.

Cardiomagnyl forte additionally contains magnesium hydroxide, which protects the mucous membranes of the digestive organs from the influence of the active substance. This xarelto substitute can be used to prevent pathologies of the heart and blood vessels in people who have hypertension, diabetes, excess weight.

The drug is also used to prevent vascular thrombosis and recurrent heart attacks. The list of indications includes unstable angina and thromboembolism after vascular surgery.

Restrictions include ulcerative lesions of the digestive system, a tendency to bleeding, complex kidney disorders, and bronchial asthma.

Xarelto belongs to the category effective drugs, which prevent the formation of blood clots and serve as a reliable prevention of strokes and heart attacks.

To achieve good results, you must strictly adhere to the doctor’s prescriptions. At the same time, the medicine has a fairly high cost. Therefore, quite often there is a need to choose more affordable analogues.

Attention, TODAY only!

In the article we will look at cheaper analogues of Xarelto.

The main purpose of the medication is to prevent the formation of blood clots that can trigger myocardial infarction. Most often, the drug is prescribed as a prophylactic agent in the period after surgery on the lower extremities. As a rule, this applies to operations on the hip and knee joints.

Xarelto is an expensive drug, so the issue of finding cheaper substitutes and analogues is very relevant. The pharmaceutical market is ready to offer a number of worthy analogues of Xarelto, some of which we will discuss below. However, the choice should be left to the attending physician, taking into account all the characteristics of the individual patient.

Composition of "Xarelto"

The drug tablet contains micronized rivaroxaban in an amount of 10, 15 or 20 mg and auxiliary components: microcrystalline cellulose, croscarmellose sodium, hypromellose 5cP, lactose monohydrate, magnesium stearate and sodium lauryl sulfate.

The film coating of the tablet shell consists of: red iron oxide dye, hypromellose 15cP, titanium dioxide and macrogol 3350.

General characteristics of the drug

Xarelto is an anticoagulant that has an inhibitory effect on platelet activity. The drug is often prescribed to patients who have suffered from multiple fractures or have undergone surgery.

Another indication for the use of Xarelto is the treatment of thrombosis, including for preventive purposes. The drug has a number of serious contraindications, so using it on its own is not recommended.

Adverse reactions

Taking Xarelto may cause such adverse reactions, How allergic dermatitis, bleeding in the eyes, soreness in the limbs and jaundice. In addition, the product can lead to a number of problems with digestive organs, namely diarrhea, vomiting, constipation, etc. Allergic reaction on the drug may be accompanied by itching, hives and skin rash.

Overdose

When using the drug, you should strictly follow the instructions of the instructions and the attending physician, since an overdose of Xarelto poses a danger to human health. In addition, it is important to follow the duration of taking the drug as prescribed by your doctor and not to prolong the course of treatment without consulting a specialist. Otherwise, numerous adverse reactions may develop.

Below we will look at analogues of Xarelto.

Russian-made analogues of the drug

Xarelto is produced in Germany, which explains its high cost. If the patient expresses a desire to purchase similar drug at a lower price, it makes sense to pay attention to the products of Russian pharmaceutical companies.

On average, the cost of one package is about 4,000 rubles, which makes the drug accessible not to everyone. Let's look at popular, cheaper Russian-made analogues of Xarelto:

1. "Vasotic." Has an antimicrobial effect. Prescribed to restore blood circulation in the brain, as well as for stroke. On average, the drug costs about 400 rubles.
2. "Gemaza". This drug is considered the best among Russian analogues of Xarelto. It is prescribed for the treatment of diseases associated with thrombosis. The price of the drug is approximately 2000 rubles.
3. "Warfarin". The most inexpensive Russian analogue original drug. It can be purchased at a pharmacy at a price of 200 rubles per package. The drug prevents the occurrence of blood clots and is prescribed for prophylactic purposes in cases of various diseases veins
4. "Fibrinolysin". This is an antithrombin drug. Its release form is a powder for preparing a special solution. The cost of the drug is approximately 600 rubles.

Thus, we can conclude that domestic pharmaceutical companies produce many worthy and affordable analogues of Xarelto. In addition to them, you can consider drugs that are produced in other countries.

Analogs from Ukraine

Ukrainian pharmaceutical companies also produce several drugs that are effective substitutes for Xarelto. The main indication for their use is venous thrombosis. It is important to carefully read the instructions before you start taking the medications listed below, as they all have a number of limitations and possible adverse reactions.

Ukraine is ready to offer the following drugs:

1. "Axparin". Anthrombic drug is produced in the form of a solution for injection. The cost is approximately 200 rubles.
2. "Dipyridamole." The most inexpensive substitute for the original drug. After transferred operations on the legs is often prescribed to prevent thrombosis. average cost tablets is 220 rubles per package.
3. "Ticlopidine." Produced in a convenient tablet form. The drug is suitable for the prevention of thrombosis of various origins. Pharmacies offer it at a price of approximately 150 rubles.
4. "Aklotin". It is the closest substitute for Xarelto. The drug is used for injection. Its cost is slightly higher than that of other Ukrainian analogues, averaging 320 rubles.

Cheap drugs, unfortunately, do not have such a pronounced therapeutic effect, as high-quality foreign funds. Therefore, when choosing the right medication, you should opt for formulations in the middle price range.

Belarusian generics

Analogues of "Xarelto" in Belarusian pharmaceutical market not so much. However, if the options described above are not suitable for one reason or another, you can pay attention to drugs such as Aspicard, produced in Belarus. The unit cost is approximately 400 rubles.

The medicinal composition has positive action on the human circulatory system and is used to prevent thrombosis. It should not be taken while pregnant, breastfeeding, or for peptic ulcers and hemorrhagic syndrome in the gastrointestinal tract.

Heparin is also inexpensive substitute"Xarelto." It helps well with diseases caused by the formation of blood clots. Its cost is approximately 100 rubles.

According to patient reviews, Venorelax is the cheapest drug - an analogue of the German medicine. It will cost only 80 rubles. It is produced in the form of a tincture and consists of natural ingredients. It cannot be used by persons under the age of 18.

"Pradaxa"

Choosing an analogue can be quite difficult, especially if there are a large number of options. Many people ask about which is better - Xarelto or Pradaxa.

Let's look at the similarities and differences between these drugs:

1. Pradaxa is a popular anticoagulant made from the active substance etexilate. This component affects thrombin, being its direct inhibitor. Xarelto is produced on the basis of rivaroxaban, which affects clotting factor Xa.
2. Pradaxa is prescribed for prophylactic purposes to prevent problems with veins that may arise after surgery on the legs. The drug can also be used for systemic embolisms and strokes.
3. Pradaxa is used several times a day, while Xarelto is used only once.
4. The dosage regimen should be determined by a doctor. Adverse reactions to taking both drugs are approximately the same, as well as contraindications.
5. The effectiveness of both drugs is also identical.

So you will have to decide for yourself which is better - Xarelto or Pradaxa.

Eliquis

You should take a responsible approach to choosing an analogue of a particular drug, since the effectiveness of the therapy will depend on this. A fairly popular analogue and substitute for Xarelto is Eliquis. Both drugs belong to the group of direct-acting anticoagulants and affect coagulation factor Xa.

The active ingredients, however, are different for the drugs. If Xarelto is produced on the basis of rivaroxaban, then the main component of Eliquis is apixaban.

But what to choose - Eliquis or Xarelto?

The main difference between the drugs is the frequency of administration of the analogue, which is prescribed to be taken twice a day. If it is more convenient for the patient to take the drug once a day, then it is better to give preference to Xarelto. Analogues and substitutes do not end there.

"Warfarin" and "Cardiomagnyl"

This drug is very often prescribed to patients in our countries as an anticoagulant. It is prescribed for thrombosis of the venous system, including for prevention purposes. In addition, the drug is used for acute infarction of the heart muscle and for heart valve replacement.

The main advantage of Warfarin is its very low cost and availability. Disadvantages include the need to adhere to special food while taking this medication.

"Cardiomagnyl" refers to non-steroidal anti-inflammatory drugs. It is based on acetylsalicylic acid. According to patient reviews, the drug copes well with pain and is also able to reduce body temperature.

Cardiomagnyl prevents platelet aggregation, so it is used during the rehabilitation period after operations, as well as to prevent myocardial infarction and thrombosis.

The average cost of Cardiomagnyl reaches a thousand rubles. This makes it an inexpensive replacement for Xarelto. However, the drug has quite a few contraindications and possible side effects, so most patients still prefer the foreign “Xarelto”.

Any drug, and Xarelto is no exception, must be prescribed in consultation with the attending physician based on an examination of the patient. This is especially true for anticoagulants, since they have an impressive list of contraindications and many restrictions when taking them. It is important to carefully read the instructions for use and reviews of Xarelto before you start taking the drug.

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 - official instructions for use

Registration number : LP-001457

Trade name

International nonproprietary name: rivaroxaban

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

Dosage form: film-coated tablets

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. Type of tablet on the break: homogeneous mass white, 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 pulmonary embolism (PE), the 5/95th percentile for prothrombin time (Neoplastin ®) 2 to 4 hours after tablet dosing (i.e., at maximum effect) ranged from 17 to 32 seconds in patients taking 15 mg twice daily and from 15 to 30 seconds in patients taking 20 mg once daily.
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 taking the whole tablet. The results demonstrated a predictable dose-dependent pharmacokinetic profile for rivaroxaban, with bioavailability at the above dosing levels consistent with those at doses above low doses 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 that 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 randomized according to the Child-Pugh classification (according to standard procedures in clinical studies). The Child-Pugh classification allows you to assess the prognosis of chronic liver diseases, 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 clinical significant risk 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 drug clearance, indicating 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);
• damage or condition associated with increased risk major bleeding, for example, an existing or recently suffered 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 breastfeeding;
• children's and adolescence up to 18 years (efficacy and safety in patients of this age group not installed);
• 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 tendency to bleeding, uncontrolled severe arterial hypertension, gastric and duodenal ulcers in the acute stage, recent gastric and duodenal ulcers, vascular history of retinopathy, bronchiectasis or 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 failure (creatinine clearance 29-15 ml/min) or increased risk of bleeding and patients receiving concomitant systemic treatment Azole antifungals or HIV protease inhibitors should be closely monitored after initiation of treatment to ensure timely detection of complications in the form of bleeding.

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 possible risk development of bleeding and the 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 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 a dose is missed, the patient should immediately take Xarelto ® and continue the next day regular intake drug 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 during 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.
Individual groups patients
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”).
The limited clinical data available in patients with moderate hepatic impairment (Child-Pugh class B) indicate a significant increase in pharmacological activity 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.
At treatment of DVT and PE and prevention of recurrent 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 appointment. parenteral administration drug (eg, low molecular weight heparin) or when continuous parenteral administration of the drug is stopped (eg, 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 lower extremity orthopedic surgery ( total endoprosthetics knee or hip joint) and 3997 patients hospitalized for medical indications treated with Xarelto ® 10 mg for up to 39 days, as well as in three phase III studies for the treatment of venous thromboembolism, including 4556 patients who received either 15 mg Xarelto ® twice daily for 3 weeks, followed by a dose of 20 mg once once a day, or 20 mg once a day for up to 21 months.
In addition, two phase III studies, including 7750 patients, provided data on the safety of the drug in patients with non-valvular atrial fibrillation treated with at least one dose of Xarelto ® for up to 41 months, and 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 acetylsalicylic acid therapy 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 hypertension and/or 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 may manifest as weakness, pallor, dizziness, headache, shortness of breath, as well as an increase in the volume 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, unwanted effects presented in decreasing order of 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 ® .
Drug interactions 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 additional information and complaints, please contact:
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