How long to take Xarelto. When is it better to take Xarelto in the morning or evening When is it better to take Xarelto in the morning or evening

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.

Xarelto and any alcohol are not compatible. What happens if you break the drinking ban? Each of us sometimes requires anticoagulants for prevention or even treatment. One of the most effective drugs in this area is Xarelto. It is aimed at treating thromboembolism and is used as a prophylactic agent to prevent stroke and heart attack. Usually, one of the most common questions among patients is “is it possible to mix the drug and alcohol?” Undoubtedly, this is a common situation when at the end of the working day you want to relax with a glass of wine, but irreversible consequences can occur if compatibility is not taken into account. Therefore, in this article we will look at what the drug is, what indications and contraindications it has, what its interaction with alcohol is, and consider several reviews about the drug itself.

Essence of Xarelto

It is a high quality selective direct inhibitor targeting:

• Stroke prevention;
• Prevention of heart attack;
• Prevention of thrombosis and embolism;
• It is a prophylactic for atrial fibrillation.

The drug is produced in the form of coated tablets of 2.5, 10, 15, 20 mg. , 10 mg, 15 mg and 20 mg. Well-known doctors recommend a 10 gram dosage, but once every 24 hours.

Basically, the appointment is made after surgery on the legs. Treatment is prescribed based on the complexity of the operation performed and the dynamics of recovery. A 35-day course is prescribed for extensive surgery in the hip joint, 14 days - if the operation was performed on the knee joint.

In a situation where the patient forgot to take the drug, doubling the dose the next day cannot be done. If he does not remember whether he took the medicine, it is better to skip the dose rather than repeat it. Reviews from many patients confirm this fact.

Main contraindications for use:

1. If there is an individual intolerance to one of the components of the drug or hypersensitivity.
2. The possibility of intracranial and other bleeding was recorded.
3. If a person is already using anticoagulants, compatibility with them is negative.
4. During pregnancy and breastfeeding, a woman is prohibited from using Xarelto.
5. For liver pathologies that are combined with poor blood clotting.
6. Until reaching adulthood, taking the drug is prohibited.
7. In the presence of mild renal failure.
8. If a person does not tolerate lactose and galactose.

It is important to monitor the patient’s condition while using the drug in the presence of the following pathologies:

1. There may be a risk of bleeding.
2. In the presence of moderate to severe renal failure, since there is a risk of bleeding.
3. It is also not recommended for use in the treatment of fungal diseases.
4. In combination with drugs that affect hemostasis.
5. Persons who are predisposed to ulcers in the stomach or duodenum should be under close medical supervision.

Main side effects

Like any other drug, Xarelto has its possible consequences:

1. Anemia (anemia);
2. Increased production of platelets in human bone marrow (thrombocythemia);
3. Heavy bleeding from an open wound;
4. Cardiopalmus;
5. A sharp decrease in blood pressure;
6. Hemorrhages leading to the formation of bruises and hematomas;
7. Possible bleeding in the stomach (hemorrhages);
8. Bleeding gums;
9. Blood from the nose and genitals;
10. Vomiting;
11. Painful vomiting, possibly with blood cells;
12. Pain on palpation of the abdominal area;
13. Swelling and discomfort in the abdominal cavity;
14. Painful digestion;
15. Dryness of mucous membranes, especially the oral cavity;
16. Weakness throughout the body, increased fatigue;
17. Fever, headaches and dizziness;
18. Allergic reactions, possible urticaria, itching or various rashes;
19. Kidney failure;
20. Increased fermentation rates in tests.

An extensive list and reviews from many patients indicate that Xarelto tablets are a chemical that can cause a lot of inconvenience to a person. The strongest effect is on the liver, because it will need to process the incoming toxin in the form of a medicine.

There have been cases of overdose, but then the listed side effects were not observed. In this case, there is no universal method of normalizing the condition or so-called antidote. You can use a unique cleaning agent - activated carbon.

Alcohol compatibility

This is the most common question among patients who are prescribed a course of this drug. In general, no drug can be combined with alcohol, but some have this option, and then the most serious consequence can only be neutralization of the effect of the tablets.

Xarelto is not classified as a drug compatible with ethanol. Their interaction cannot be called fatal, but taking two substances together is not recommended. Alcohol can drown out all the actions of the anticoagulant and the effect of the impact; this aspect can affect the person’s recovery process, and possibly aggravate his illness.

Alcohol affects the rhythm of the heart muscle, absolutely negatively, and the situation that occurs when mixed with the drug can lead to a heart attack, which the drug is aimed at preventing. We can say that these two substances are aimed at completely opposite actions.

Reviews from many researchers indicate that alcohol causes sudden surges in blood pressure as blood vessels dilate. As soon as ethanol leaves the blood, it immediately rises. This unstable situation will negatively affect the effect of Xarelto, and its side effects include the presence of low blood pressure.

If a person has a pathology associated with cardiac dysfunction, then in fact he is prohibited from taking the drug, even in the smallest quantities. The interaction of a drug, alcohol and a weakened body can lead to a heart attack or stroke, and Xarelto is aimed at treating these diseases. Even if a person is not affected by this disease, then heart failure is only guaranteed.

No drug will have excellent compatibility with alcohol; you should not combine them. It doesn’t even matter what drink was consumed: whiskey, vodka or ordinary medicinal tincture. If it contains at least one percent ethanol, you should stop taking it.

It is impossible to describe the entire list of possible consequences; they depend on the individual susceptibility of the human body. In addition, it is important to consider what the alcoholic drink is made from. Perhaps the drug will react negatively not to ethyl alcohol itself, but to some additional ingredient. Therefore, it is impossible to predict how the body will behave.

As already mentioned, compatibility is not fatal, but this does not give the patient the opportunity to drink continuously. An acceptable dose (but not recommended) is 1 glass of dry red wine. It will speed up blood circulation without aggravating the person’s situation.

When treating any disease, it is important to stop drinking any alcoholic beverages, since they provoke the development of a particular disease.

It is important to remember the effects of both drugs and alcohol on the liver. By taking a certain drug, no matter for what purpose, you will cause some minor damage to the liver. When drinking alcohol, hepatocytes die, connective tissue is formed, and if abused, the organ can simply fail. It turns out that as soon as the tablet entered the body, the liver began to work on breaking it down, then ethanol enters, which also requires digestion. The organ begins to work to the limit of its capabilities, thereby causing various negative consequences for the person.

They have been living with paroxysmal atrial fibrillation for 7 years, which is accompanied by frequent attacks. At first I took aspirin, but three years ago I was prescribed Xarelto 20 mg. I noticed that the attacks became much weaker, it became a little easier. But I noticed a lot of side effects:

1. The drug removes calcium, which is necessary at my age, so now I live with osteoporosis and a vertebral fracture.
2. I have not been able to cure herragic cystitis for several years now.
3. The mouth is constantly dry, sometimes there is blood
4. Bruises and bruises appear.

Almost everyone advises switching to Warfarin, but even it has the same side effects, although the price is lower. By the way, another significant disadvantage of the drug is the prohibitive price for a person who lives on one pension.

Valentina. My husband is 33 years old, a former athlete.

As a result of a fracture of the knee joint, thrombosis of a vein in his leg occurred, almost from the toes of his right foot to the groin area (soon it reached the abdominal cavity. Due to the deep conviction that “everything will go away on its own,” he suffered from unpleasant sensations for a week. I forced him to go to clinic, where the only answer was “this case is hopeless, you can rely on the effect of Claresto." We drank a month course, 10 ml twice a day, the test showed that there was a positive trend. Of course, the merit of the drug is there, but we also resorted to the help of alternative medicine. I gave my husband Iodinol to drink, made compresses from oak leaves. You cannot give up even in the most hopeless situations!

Marina 59 years old

I've been taking Xarelto for about 11 months. My diagnosis: thrombosis of the veins of the legs, I underwent two surgical interventions. They prescribed me Xarelto for life, sometimes I check for hemostasis. Although they said that you will need treatment for the rest of your life, I read that you can only drink it for a year. Doubts crept in, but apart from the high price, I didn’t notice any shortcomings.

Vladislav 58 years old

I was admitted with a diagnosis of pulmonary edema and was diagnosed with arrhythmia. I was prescribed a course of Xarelto. I did not experience a heart attack or stroke, and also did not notice any side effects. The only thing that is a little confusing is the price of the drug.

Valeria 64 years old

A fracture of the femoral neck was diagnosed and there were numerous burns. There were complications in the form of thrombosis, and then I was prescribed Xarelto. I drank it for about 60 days, the swelling subsided greatly, the doctor said that improvement was expected, because... there is a positive trend. The only thing is that it is rare to find dosages of 10 ml, and besides, the price is high.

alcoholism.com

Xarelto

Xarelto is a direct-acting anticoagulant, a selective factor Xa inhibitor.

Release form and composition

The dosage form of Xarelto is film-coated tablets: round, biconvex, on one side the Bayer logo in the form of a cross is applied by extrusion, on the other there is a triangle with the dosage designation (“2.5”, “10”, “15” or “20” ), in cross section the kernel is white:

• 2.5 mg: 10 pcs. blisters, 10 blisters in a cardboard pack; 14 pcs. in blisters, in a cardboard pack of 1, 2, 4, 7, 12 or 14 blisters;
• 10 mg: 5 pcs. in blisters, in a cardboard box 1 blister; 10 pcs. in blisters, in a cardboard pack 1, 3 or 10 blisters;
• 15 mg: 10 pcs. blisters, 10 blisters in a cardboard pack; 14 pcs. in blisters, in a cardboard pack 1, 2 or 3 blisters;
• 20 mg: 10 pcs. blisters, 10 blisters in a cardboard pack; 14 pcs. in blisters, in a cardboard pack 1 or 2 blisters.

The active ingredient of the drug is rivaroxaban (micronized). Its content in tablets depending on the color of the shell:

• Light yellow – 2.5 mg;
• Pink – 10 mg;
• Pink-brown – 15 mg;
• Red-brown – 20 mg.

Auxiliary components: sodium lauryl sulfate, croscarmellose sodium, microcrystalline cellulose, magnesium stearate, lactose monohydrate, hypromellose 5cP.

Shell composition: hypromellose 15cP, macrogol 3350, titanium dioxide and dye (in tablets 2.5 mg - yellow iron oxide, in the rest - red iron oxide).

Indications for use

For 2.5 mg tablets (in combination with acetylsalicylic acid (ASA) or ASA and thienopyridines - ticlopidine or clopidogrel):

• Prevention of mortality due to cardiovascular complications and myocardial infarction in patients after acute coronary syndrome (ACS), accompanied by an increase in cardiac-specific biomarkers.

For 10 mg tablets:

• Prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery of the lower extremities.

For 15 and 20 mg tablets:

• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), prevention of their relapses;
• Prevention of systemic thromboembolism and stroke in patients with non-valvular atrial fibrillation.

Contraindications

All dosage forms of Xarelto are contraindicated in the following cases:

• Clinically significant active bleeding (eg, gastrointestinal or intracranial);
• Severe renal failure (with creatinine clearance (CC) less than 15 ml/minute);
• Liver diseases accompanied by coagulopathy, which increases the risk of developing clinically significant bleeding, incl. functional liver disorders class B and C in accordance with the Child-Pugh classification, liver cirrhosis;
• Glucose-galactose malabsorption, congenital lactase deficiency or lactose intolerance;
• The need for therapy with other anticoagulants, such as heparin derivatives (including fondaparinux), oral anticoagulants (including apixaban, warfarin, dabigatran), low molecular weight heparins (including dalteparin and enoxaparin) and unfractionated heparin, with the exception of cases of transfer of the patient from/to rivaroxaban or use of unfractionated heparin in doses necessary to ensure the functioning of the central arterial or venous catheter;
• Age up to 18 years;
• Pregnancy;
• Lactation;
• Hypersensitivity to the components of the drug.

Additional contraindications depending on the dose of Xarelto:

• 2.5 mg tablets: treatment of ACS with antiplatelet agents in patients who have suffered a stroke or transient ischemic attack;
• 15 and 20 mg tablets: conditions or injuries associated with a high risk of major bleeding, such as recent brain or spinal cord injury, recent or existing gastrointestinal ulcer, diagnosed or suspected esophageal varices, intracranial hemorrhage, high-risk malignancy bleeding, surgery on the eyes, spinal cord or brain, vascular aneurysms or vascular pathologies of the brain/spinal cord, arteriovenous malformations.

Xarelto is used with extreme caution in the following cases:

• Increased risk of bleeding: vascular retinopathy, exacerbation or recent acute peptic ulcer of the stomach and duodenum, bronchiectasis or history of pulmonary hemorrhage, uncontrolled severe arterial hypertension, congenital or acquired tendency to bleeding, vascular pathologies of the brain or spinal cord, recent intracranial or intracerebral hemorrhage, recent surgery on the eyes, spinal cord or brain;
• Moderate renal failure (creatinine clearance 30-49 ml/minute) in patients receiving drugs that increase the concentration of rivaroxaban in the blood plasma;
• Severe renal failure (creatinine clearance from 15 to 29 ml/minute);
• Concomitant use of drugs that affect hemostasis (for example, antiplatelet agents or other antithrombotic agents, nonsteroidal anti-inflammatory drugs);
• Concomitant use of systemic azole antifungals (for example, ketoconazole) or human immunodeficiency virus protease inhibitors.

Directions for use and dosage

Xarelto 2.5 mg is taken 1 tablet 2 times a day, regardless of meals.

The drug is prescribed as soon as possible after stabilization of the patient's condition with OSK (including the revascularization procedure), no earlier than 24 hours after hospitalization, after the end of parenteral administration of anticoagulants.

Patients are also prescribed acetylsalicylic acid (ASA) at a daily dose of 75-100 mg or ASA at 75-100 mg/day in combination with clopidogrel at a dose of 75 mg/day or ticlopidine at a standard daily dose.

The duration of therapy is 12 months, for some patients it can be extended to 24 months. The risk ratio of ischemic events and bleeding should be regularly assessed throughout the treatment period.

If you miss the next dose, you should not double the dose; you must take the next dose at the scheduled time.

Xarelto 10 mg is taken 1 tablet 1 time per day, regardless of meals. Provided hemostasis has been achieved, the first tablet should be taken 6-10 hours after surgery.

Duration of treatment:

• After major knee surgery – 2 weeks;
• After major hip surgery – 5 weeks.

If you miss the next dose, you must take the pill immediately and continue treatment the next day as before.

Xarelto 15 and 20 mg is taken with food.

For the prevention of systemic thromboembolism and stroke in patients with non-valvular atrial fibrillation, the drug is prescribed 20 mg once a day, in case of renal failure - 15-20 mg once a day.

When treating DVT and PE and preventing their relapses, 15 mg 2 times a day is prescribed during the first 3 weeks, then the dose is increased to 20 mg 1 time a day.

Maximum permissible daily doses: during treatment - 30 mg (during the first 3 weeks), for further prevention - 20 mg.

The duration of treatment in each case is determined individually, after a careful assessment of the balance between the benefits of therapy and the possible risks of bleeding. The minimum course is 3 months and is based on an assessment of reversible factors, such as trauma, previous surgery, and a period of immobilization. The doctor may decide to extend the duration of treatment in the event of the development of idiopathic pulmonary embolism or deep venous thromboembolism or after identifying persistent risk factors.

If the next dose is missed by a patient taking Xarelto at a dose of 15 mg 2 times a day, it is necessary to take the missed dose as quickly as possible in order to achieve the daily dose of 30 mg, i.e. both tablets can be taken at one time. The next day you need to continue regular use in accordance with the recommended regimen.

If the next dose is missed by a patient taking Xarelto at a dose of 20 mg 1 time per day, he should take the drug immediately, and the next day continue regular use in accordance with the prescribed regimen.

For any patients who have difficulty swallowing whole tablets, they can be crushed or mixed with water/liquid food (eg, applesauce) immediately before administration.

If necessary, a crushed tablet with a small amount of water can be administered through a gastric tube (the position of which must be agreed with the doctor), after which a little water should be introduced to wash off the remaining drug from the walls of the tube. After taking Xarelto at a dose of 15 or 20 mg, you should immediately receive enteral nutrition.

Side effects

• Hematopoietic system: often – anemia, infrequently – thrombocythemia (including increased platelet count)*;
• Cardiovascular system: often – hematoma, arterial hypotension; infrequently - tachycardia;
• Digestive system: often – pain in the gastrointestinal tract, dyspepsia, gastrointestinal bleeding (including rectal), nausea, bleeding gums, diarrhea, vomiting*, constipation*; uncommon – dry mouth;
• Nervous system: often – dizziness and headache; infrequently – short-term fainting, intracerebral and intracranial hemorrhage;
• Organ of vision: often – hemorrhage in the eye (including in the conjunctiva);
• Liver: uncommon – functional liver disorder; rarely – jaundice;
• Genitourinary system: renal failure (including increased concentrations of creatinine and urea)*, bleeding from the urogenital tract (including menorrhagia and hematuria**);
• Immune system: uncommon – allergic dermatitis, allergic reactions;
• Respiratory system: often – hemoptysis, nosebleeds;
• Musculoskeletal system: often – pain in the limbs*; infrequently - hemarthrosis; rarely - hemorrhage into the muscles;
• Skin and subcutaneous tissues: often - skin and subcutaneous hemorrhages, rash, ecchymosis, itching; uncommon – generalized itching, urticaria;
• From the body as a whole: deterioration in general health (including weakness and asthenia), peripheral edema, fever*; infrequently – malaise and anxiety; rarely – local swelling*;
• Laboratory indicators: often - increased transaminase levels; uncommon – increased activity of alkaline phosphatase, lipase, amylase, gamma-glutamyltransferase and lactate dehydrogenase*, increased bilirubin concentration; rarely - an increase in the concentration of conjugated bilirubin (including with a concomitant increase in alanine aminotransferase activity);
• Other: often - excessive hematoma due to a bruise, hemorrhages after procedures (including bleeding from a wound and postoperative anemia); uncommon – discharge from the wound*; rarely – vascular pseudoaneurysm***.

* – these side effects were recorded after major orthopedic surgeries.

** - these adverse reactions were recorded during the treatment of VTE as very common in women under 55 years of age.

*** – these events were recorded as infrequent in the prevention of myocardial infarction and sudden death in patients after acute coronary syndrome (after percutaneous interventions).

special instructions

When performing spinal/epidural anesthesia or lumbar puncture in patients taking platelet aggregation inhibitors to prevent thromboembolic complications, there is a risk of developing a spinal or epidural hematoma, which can lead to long-term paralysis. This risk subsequently increases with concomitant therapy with drugs that affect hemostasis and with the use of a permanent epidural catheter. Traumatic spinal or epidural puncture may also increase the risk. For timely diagnosis of symptoms of neurological disorders (for example, bladder or bowel dysfunction, numbness or weakness of the legs), patients should be under constant medical supervision. The epidural catheter should be removed no earlier than 18 hours after the last dose of Xarelto. The drug is prescribed no earlier than 6 hours after removing the catheter. In case of a traumatic puncture, the use of rivaroxaban should be postponed for 24 hours.

If an invasive procedure or surgery is necessary, Xarelto should be discontinued at least 24 hours in advance. If the procedure/surgery cannot be postponed, the increased risk of bleeding should be weighed against the need for urgent intervention. After the procedure, you can resume taking the drug only if there is adequate hemostasis and the presence of clinical indicators.

Patients at risk of developing gastric and/or duodenal ulcers can be prescribed appropriate preventive therapy.

Xarelto is not recommended for use as an alternative to unfractionated heparin in unstable PE, or when thrombolysis or thrombectomy is required, since the efficacy and safety of rivaroxaban in these clinical situations have not been established.

Fainting and dizziness may occur when taking Xarelto. Patients who experience these reactions should refrain from driving or performing potentially hazardous activities.

Drug interactions

With the simultaneous use of strong inhibitors of the CYP3A4 isoenzyme and P-glycoprotein, a decrease in hepatic and renal clearance and an increase in systemic exposure are observed, so they must be used with caution.

Ketoconazole enhances the pharmacodynamic effect of Xarelto, while rifampicin reduces it.

The simultaneous use of the drug with dronedarone should be avoided, because Clinical data on this combination are limited.

Ritonavir increases the maximum concentration of rivaroxaban by 1.6 times, which is accompanied by a significant increase in its pharmacodynamic effect, and therefore this combination is not recommended.

With simultaneous use of rivaroxaban with enoxaparin sodium (in a single dose of 40 mg), a summative effect was noted regarding the activity of anti-Xa factor.

Any other anticoagulants should be used with extreme caution, because high risk of bleeding.

When Xarelto 15 mg was taken in combination with clopidogrel (at a loading dose of 300 mg followed by a maintenance dose of 75 mg), no pharmacokinetic interaction was observed, but in a subgroup of patients a significant increase in bleeding time was detected, which was not correlated with P-selectin or GPIIb/IIIa receptor and the degree of platelet aggregation.

In some cases, with simultaneous administration of naproxen at a dose of 500 mg, a pronounced pharmacodynamic response is possible.

Platelet aggregation inhibitors and non-steroidal anti-inflammatory drugs (including acetylsalicylic acid) increase the risk of bleeding.

When transferring a patient from warfarin to rivaroxaban and vice versa, the prothrombin time increases.

If possible, it is recommended to avoid transferring patients from phenindione to rivaroxaban and vice versa, because Experience with this application is very limited. If such a need is justified, then the pharmacodynamic effect of the drugs (prothrombin time, MHO) should be monitored daily immediately before taking the next dose of Xarelto.

Terms and conditions of storage

Store at temperatures up to 30 ºС out of the reach of children.

Shelf life – 3 years.

spravka03.net

Xarelto - instructions for use, analogues, reviews

Xarelto is a direct acting anticoagulant. Available in the form of film-coated tablets containing 10, 15 and 20 milligrams of the active substance. The active substance is micronized rivaroxaban.

Pharmacological action and pharmacodynamics

According to the instructions, Xarelto inhibits factor Xa and also has an anticoagulant effect.

The mechanism of action of Xarelto according to the instructions is direct inhibition of factor Xa. Rivaroxaban is highly selective and has high bioavailability (80-100 percent) when administered orally. Activation through the extrinsic and intrinsic coagulation pathways of factor X to form factor Xa plays the most important role in the coagulation cascade.

Pharmacokinetics

Rivaroxaban is rapidly absorbed - the maximum concentration in the blood is reached within two to four hours after taking the tablet. Once ingested, most rivaroxaban (92 to 95 percent) is bound to plasma proteins, the main binding component being serum albumin.

When administered orally, approximately two-thirds of a dose of rivaroxaban is metabolized and subsequently excreted in equal parts in feces and urine. The remaining third is excreted unchanged by direct renal excretion, primarily due to active renal secretion.

Indications for use of Xarelto

According to the instructions, Xarelto in the form of 10-milligram tablets is indicated for the prevention of venous thromboembolism in people who have undergone major orthopedic surgery on the lower extremities.

Xarelto tablets of 15 and 20 milligrams are indicated for the prevention of systemic thromboembolism and stroke in people with non-valvular atrial fibrillation, as well as for the treatment of pulmonary embolism and deep vein thrombosis, for the prevention of recurrent PE and DVT.

Contraindications to the use of Xarelto

According to the instructions, Xarelto is contraindicated in:

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

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. Factor Xa is a component of the developing prothrombinase complex, the action of which leads to the conversion of prothrombin into thrombin. As a result, these reactions lead to the formation of a fibrin thrombus and activation of platelets by thrombin. One molecule of factor Xa catalyzes the formation of more than 1000 molecules of thrombin, which is called the “thrombin burst”. The reaction rate of factor Xa bound in prothrombinase is increased 300,000 times compared to that of free factor Xa, which provides a sharp jump in thrombin levels. Selective factor Xa inhibitors can stop the thrombin burst. Therefore, rivaroxaban may interfere with the results of some specific or general laboratory tests used to evaluate coagulation systems. In humans, dose-dependent inhibition of factor Xa activity is observed.

Pharmacodynamic effects

In humans, dose-dependent inhibition of factor Xa was observed. Rivaroxaban has a dose-dependent effect on changes in prothrombin time, which closely correlates with rivaroxaban plasma concentrations (correlation coefficient 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 MHO is calibrated and certified only for coumarin derivatives and cannot be used for other anticoagulants.

In patients undergoing major orthopedic surgery, the 5/95th percentile for prothrombin time (Neoplastin®) 2-4 hours after taking the tablet (i.e., at maximum effect) ranges from 13 to 25 seconds.

Also, rivaroxaban dose-dependently increases APTT and HepTest ® result; however, these parameters are not recommended for assessing the pharmacodynamic effects of rivaroxaban. Rivaroxaban also affects anti-factor Xa activity, but there are no standards for calibration.

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 QT interval on the ECG under the influence of rivaroxaban was not observed.

Pharmacokinetics

Suction

After oral administration, rivaroxaban is rapidly absorbed; Cmax is achieved 2-4 hours after taking the tablet.

After oral administration, rivaroxaban is absorbed quickly and almost completely. Cmax is achieved 2-4 hours after taking the tablet. The bioavailability of rivaroxaban when taking 2.5 mg and 10 mg tablets is high (80-100%), regardless of food intake. Food intake does not affect AUC and C max when taking the drug at a dose of 10 mg. Xarelto ® 2.5 mg and 10 mg tablets can be taken with food or on an empty stomach.

The pharmacokinetics of rivaroxaban is characterized by moderate interindividual variability, the coefficient of variability Cv% ranges from 30% to 40%.

Distribution

Rivaroxaban has a high degree of binding to plasma proteins - approximately 92-95%, mainly rivaroxaban binds to serum albumin. The drug has an average Vd of approximately 50 l.

Metabolism and excretion

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 in vitro data, 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 plasma; 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.

Removal

When rivaroxaban is eliminated from plasma, the final T1/2 ranges from 5 to 9 hours in young patients and from 11 to 13 hours in elderly patients.

Pharmacokinetics in special clinical situations

Age. In elderly patients over 65 years of age, plasma concentrations of rivaroxaban are higher than in younger patients, with a mean AUC value approximately 1.5 times higher than in younger patients, mainly due to an apparent decrease in total and renal clearance.

Floor. No clinically significant differences in pharmacokinetics were found in men and women.

Body mass. Too little or too much body weight (less than 50 kg and more than 120 kg) has only a small effect on the plasma concentration of rivaroxaban (the difference is less than 25%).

Childhood. Data on pharmacokinetics in children are not available.

Interethnic differences. Clinically significant differences in pharmacokinetics and pharmacodynamics were not observed in patients of Caucasian, Negroid, Asian, or Hispanic, Japanese or Chinese ethnicity.

Liver dysfunction. The effect of hepatic impairment on the pharmacokinetics of rivaroxaban was studied in patients classified according to the Child-Pugh classification (according to standard procedures in clinical trials). The Child-Pugh classification allows you to assess the prognosis of chronic liver diseases, mainly cirrhosis. In patients undergoing anticoagulant therapy, a particularly important critical point in liver dysfunction is the decrease in the synthesis of coagulation factors in the liver. Because 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 cirrhosis of the liver with mild liver failure (class A according to the Child-Pugh classification), the pharmacokinetics of rivaroxaban differed only slightly from the corresponding indicators in the control group of healthy volunteers (on average, there was an increase in AUC of rivaroxaban by 1.2 times). There were no significant differences in pharmacodynamic properties between groups.

In patients with cirrhosis and moderate hepatic impairment (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 liver disease. 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 on the use of the drug in patients with class C hepatic impairment according to the Child-Pugh classification. Therefore, in patients with liver cirrhosis and impaired liver function B and C according to the Child-Pugh classification, rivaroxaban is contraindicated.

Renal dysfunction. In patients with renal failure, an increase in rivaroxaban exposure was observed, inversely proportional to the degree of decrease in renal function, which was assessed by CC.

In patients with renal failure of mild (creatinine clearance 50-80 ml/min), moderate (creatinine clearance 30-49 ml/min) or severe (creatinine clearance 15-29 ml/min) severity, a 1.4-, 1.5- and 1.6-fold increase was observed rivaroxaban plasma concentrations (AUC), respectively, compared with healthy volunteers. The corresponding increase in pharmacodynamic effects was more pronounced.

In patients with mild, moderate and severe renal failure, the overall suppression of factor Xa activity increased by 1.5, 1.9 and 2 times compared with healthy 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 CC 15-29 ml/min are limited, and therefore caution should be exercised when using the drug in this category of patients. Data on the use of rivaroxaban in patients with CC<15 мл/мин отсутствуют, в связи с чем не рекомендуется применять препарат у данной категории пациентов.

Release form

Light yellow, film-coated tablets, round, biconvex; on one side, a triangle with the dosage designation “2.5” is applied by extrusion; on the other side, the Bayer logo in the form of a cross; On a cross section, the core is white.

Excipients: microcrystalline cellulose - 40 mg, croscarmellose sodium - 3 mg, hypromellose 5cP - 3 mg, lactose monohydrate - 35.7 mg, magnesium stearate - 0.6 mg, sodium lauryl sulfate - 0.2 mg.

Film shell composition: yellow iron oxide dye - 0.015 mg, hypromellose 15cP - 1.5 mg, macrogol 3350 - 0.5 mg, titanium dioxide - 0.485 mg.

10 pieces. - blisters (10) - cardboard packs.
14 pcs. - blisters (1) - cardboard packs.
14 pcs. - blisters (2) - cardboard packs.
14 pcs. - blisters (4) - cardboard packs.
14 pcs. - blisters (7) - cardboard packs.
14 pcs. - blisters (12) - cardboard packs.
14 pcs. - blisters (14) - cardboard packs.

Dosage

Take 2.5 mg orally (1 tablet) 2 times a day, regardless of meals.

After acute coronary syndrome, the recommended dose of Xarelto ® is 2.5 mg (1 tablet) 2 times a day. Patients also need to take acetylsalicylic acid at a dose of 75-100 mg/day or acetylsalicylic acid at a dose of 75-100 mg/day in combination with clopidogrel at a dose of 75 mg/day or ticlopidine at a standard daily dose.

Treatment should be regularly assessed to ensure the balance between the risk of ischemic events and the risk of bleeding. The duration of treatment is 12 months. Treatment may be extended to 24 months for selected patients, as data on treatment for this duration are limited.

Treatment with Xarelto ® at a dose of 2.5 mg should be started as soon as possible after the patient's condition has stabilized during the current ACS (including revascularization procedures). Treatment with Xarelto ® should begin at least 24 hours after hospitalization. Xarelto ® 2.5 mg should be started when parenteral anticoagulants are usually stopped.

If a dose is missed, you should continue taking the drug at a dose of 2.5 mg at the next scheduled dose.

If the patient is unable to swallow the tablet whole, the Xarelto ® tablet may be crushed or mixed with water or a liquid food such as applesauce immediately before administration. A crushed Xarelto ® tablet can be given through a gastric tube. The position of the probe in the gastrointestinal tract must be additionally 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.

Limited clinical data obtained in patients with moderate hepatic impairment (Child-Pugh class B) indicate a significant increase in pharmacological activity. For patients with severe hepatic impairment (Child-Pugh class C), no clinical data are available.

< 15 мл/мин.

Switching from Vitamin K Antagonists (VKAs) to Xarelto ® : When patients switching from VKAs to Xarelto ® , MHO values ​​will be erroneously elevated after taking Xarelto ® . MHO is not suitable for determining the anticoagulant activity of Xarelto ® , so this indicator is not used for this purpose.

Switching from therapy with Xarelto ® to therapy with vitamin K antagonists: there is a possibility of insufficient anticoagulant effect when switching from therapy with Xarelto ® to VKA therapy. 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 during the transition from therapy with Xarelto ® to VKA therapy, Xarelto ® may help increase MHO.

In patients switching from Xarelto therapy to VKA therapy, the latter should be taken continuously until the MHO value is ≥2.0. In the first 2 days of the transition period, VKA should be used in standard doses, subsequently adapting the dose of VKA in accordance with the MHO value. Because During this period, patients receive both Xarelto ® and VKA simultaneously; MHO should be assessed no earlier than 24 hours later (after the first dose, but before the next dose of Xarelto ®). Therefore, after stopping use of Xarelto ® , MHO can be used as a reliable assessment of the therapeutic effect of VKA no earlier than 24 hours after the last dose of Xarelto ® .

Switching from parenteral anticoagulant therapy to therapy with Xarelto ® : For 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 anticoagulant therapy: Discontinue Xarelto ® and administer the first dose of parenteral anticoagulant at the time the next dose of Xarelto ® is due.

The safety and effectiveness of the drug in children and adolescents under 18 years of age have not been established.

In elderly patients, no dose adjustment is required.

No dose adjustment of Xarelto is required depending on gender, body weight, or ethnicity.

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, plateau concentrations are expected without a further increase in mean plasma concentrations of rivaroxaban when administered in excessive doses of 50 mg or higher.

Treatment: A specific antidote for rivaroxaban is unknown. In case of Xarelto ® overdose, activated charcoal can be used to reduce the absorption of rivaroxaban. Due to the significant binding of rivaroxaban to plasma proteins, rivaroxaban is not expected to be eliminated by hemodialysis.

If a complication occurs in the form of bleeding, the next dose of the drug should be postponed or treatment with the drug should be discontinued altogether. T1/2 of rivaroxaban lasts approximately 5-13 hours. Treatment should be selected individually, depending on the severity and location of bleeding.

If necessary, appropriate symptomatic treatment can be carried out, such as mechanical compression (for example, for severe nosebleeds), surgical hemostasis with evaluation of its effectiveness (bleeding control), fluid therapy and hemodynamic support, the use of blood products (packed red blood cells or fresh frozen plasma, depending on whether anemia or coagulopathy occurred) or platelets.

If the above measures do not eliminate bleeding, specific reverse-acting procoagulant agents such as prothrombin complex concentrate, activated prothrombin complex concentrate, or recombinant factor VIIa can be used. 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 no experience with the use of antifibrinolytic drugs (tranexamic acid, aminocaproic acid) in patients receiving Xarelto ® . There is no scientific basis for or experience with the use of systemic hemostatic drugs desmopressin and aprotinin in patients receiving Xarelto ® .

Interaction

Pharmacokinetic interaction

Elimination of rivaroxaban occurs primarily through hepatic metabolism mediated by CYP3A4 and CYP2J2 isoenzymes, as well as renal excretion of unchanged drug via P-glycoprotein/Bcrp.

Rivaroxaban does not inhibit or induce CYP3A4 or any other major isoenzymes of the cytochrome P450 system.

Concomitant use of Xarelto and potent inhibitors of CYP3A4 and P-glycoprotein may result in decreased renal and hepatic clearance and thus significantly increase systemic exposure.

The simultaneous use of the drug Xarelto ® and the azole antifungal drug ketoconazole (400 mg 1 time / day), a powerful 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 Cmax of rivaroxaban by 1.7 times, which was accompanied by a significant enhancing the pharmacodynamic effects of Xarelto ® .

The simultaneous use of Xarelto ® with the HIV protease inhibitor ritonavir (600 mg 2 times / day), which is a strong 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 effects of the drug.

Other active substances that inhibit at least one of the elimination pathways of rivaroxaban, mediated by either CYP3A4 or P-gp, are likely to increase rivaroxaban plasma concentrations to a lesser extent.

Clarithromycin (500 mg 2 times/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 of the order of normal variability in AUC and Cmax and is considered clinically insignificant.

Erythromycin (500 mg 3 times/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 of the order of normal variability in AUC and Cmax and is considered clinically insignificant.

Fluconazole (400 mg 1 time / day), a moderate inhibitor of the CYP3A4 isoenzyme, caused an increase in the average AUC of rivaroxaban by 1.4 times and an increase in the average Cmax by 1.3 times. This increase is of the order of normal variability in AUC and Cmax and is considered clinically insignificant.

The simultaneous use of Xarelto ® and rifampicin, which is a strong inducer of CYP3A4 and P-glycoprotein, led to a decrease in the average AUC of rivaroxaban by approximately 50% and a parallel decrease in its pharmacodynamic effects. Concomitant use of Xarelto with other strong CYP3A4 inducers (for example, phenytoin, carbamazepine, phenobarbital or St. John's wort) may also result in decreased plasma concentrations of rivaroxaban.

Potent CYP3A4 inducers should be used with caution in patients after ACS receiving Xarelto ® 2.5 mg 2 times a day.

Pharmacodynamic interaction

After simultaneous use of enoxaparin sodium (40 mg once) and the drug Xarelto ® (10 mg once), a summative effect of suppressing the activity of anti-factor Xa was observed without any additional effect on coagulation parameters (prothrombin time, aPTT). Enoxaparin does not affect the pharmacokinetics of rivaroxaban.

There was no pharmacokinetic interaction between clopidogrel (loading dose of 300 mg followed by a maintenance dose of 75 mg) with Xarelto ® (at a dose of 15 mg), however, a significant increase in bleeding time was recorded in a subgroup of patients, which did not correlate with the degree of platelet aggregation, the number of receptors to P-selectin or GPIIb/IIIa.

After simultaneous use of Xarelto ® (15 mg) and naproxen (500 mg), no clinically significant prolongation of bleeding time was observed. However, a more pronounced pharmacodynamic response is possible in some patients.

Caution should be exercised when rivaroxaban is used concomitantly with dronedarone due to limited clinical data on coadministration.

Due to the increased risk of bleeding, caution is required when used together with any other anticoagulants.

Use Xarelto ® with caution in combination with NSAIDs (including acetylsalicylic acid) and antiplatelet agents, since the use of these drugs usually increases the risk of bleeding.

Switching patients from warfarin (IHO 2 to 3) to Xarelto ® (20 mg) or from Xarelto ® (20 mg) to warfarin (MHO 2 to 3) increased prothrombin time/INR (Neoplastin) more than with simple summation effects (individual INR values ​​can reach 12), while the effects of changes in aPTT, suppression of factor Xa activity and endogenous thrombin potential (EPT) were additive.

If it is necessary to study the pharmacodynamic effects of Xarelto ® during the transition period, anti-factor Xa activity, prothrombinase-induced clotting time and Hep Test ® can be used as necessary tests that are not affected by warfarin. Starting from the 4th day after discontinuation of warfarin, all tests (including prothrombin time, aPTT, suppression of factor Xa activity and EPT (endogenous thrombin potential)) reflect only the effect of the drug Xarelto ® .

To assess the pharmacodynamic effects of warfarin during the transition period, the MHO measured at the time the rivaroxaban Cmax is reached (24 hours after dosing with rivaroxaban) can be used, since at this point in time rivaroxaban has virtually no effect on this indicator.

No pharmacokinetic interaction has been reported between warfarin and Xarelto ® .

No interaction

There is no pharmacokinetic interaction between rivaroxaban and midazolam (CYP3A4 substrate), digoxin (P-glycoprotein substrate) or atorvastatin (CYP3A4 and P-glycoprotein substrate).

Concomitant use of the proton pump inhibitor omeprazole, the histamine H2 receptor blocker ranitidine, the antacid aluminum hydroxide/magnesium hydroxide, naproxen, clopidogrel or enoxaparin does not affect the bioavailability and pharmacokinetics of rivaroxaban.

No clinically significant pharmacokinetic and pharmacodynamic interactions were identified when taking Xarelto ® and acetylsalicylic acid at a dose of 500 mg in combination.

Effect on laboratory parameters

Xarelto ® affects blood clotting parameters (prothrombin time, APTT, Hep Test ®) due to its mechanism of action.

Side effects

The safety of Xarelto ® was assessed in four phase III studies involving 6097 patients undergoing major lower extremity orthopedic surgery (total hip replacement or total knee replacement) and 3997 patients hospitalized for medical reasons treated with Xarelto ® 10 mg for up to 39 days. days, as well as in 2 phase III studies for the treatment of venous thromboembolism, including 2194 patients who received Xarelto ® either 15 mg 2 times / day for 3 weeks, followed by a dose of 20 mg 1 time / day, or 20 mg 1 time /day with a treatment duration of 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 ® , as well as 10,225 patients with ACS who received, at least one dose of Xarelto ® 2.5 mg (2 times/day) or 5 mg (2 times/day) of Xarelto ® in combination with either acetylsalicylic acid or acetylsalicylic acid with clopidogrel or ticlopidine.

Due to the pharmacological 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 severe uncontrolled arterial hypertension and/or when used together with drugs that affect hemostasis.

Signs, symptoms, and severity (including possible death) vary depending on the location, intensity, or duration of bleeding and/or anemia.

Hemorrhagic complications may include weakness, pallor, dizziness, headache, unexplained swelling, shortness of breath, or shock that cannot be explained by other causes. 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 Xarelto. Therefore, the possibility of bleeding should be considered when assessing the condition of a patient receiving anticoagulants.

A summary of the incidence of adverse reactions reported for Xarelto ® is given below. In groups divided by frequency, undesirable effects are presented in order of decreasing severity, as follows: very often (≥1/10); often (≥1/100 -<1/10); нечасто (≥1/1000 - <1/100); редко (≥1/10 000 - <1/1000).

Table. All treatment-emergent adverse drug reactions recorded in patients in phase III clinical trials (cumulative data RECORD 1-4, EINSTEIN-DVT (deep vein thrombosis), ROCKET AF, J-ROCKET AF, MAGELLAN, ATLAS and EINSTEIN (DVT/ PE/Extension)

A - observed mainly after major orthopedic surgeries

B - observed in the treatment of VTE as very common in older women<55 лет

C - observed as infrequent as part of the prevention of complications in ACS (after percutaneous interventions)

The most common adverse reactions in patients receiving the drug were bleeding. The most common bleeding events (≥4%) were epistaxis (5.9%) and gastrointestinal bleeding (4.2%).

Overall, 67% of patients who received at least one dose of rivaroxaban experienced an adverse reaction requiring therapy. In approximately 22% of patients, according to the researchers, adverse reactions were related to the use of the drug. When using Xarelto ® 10 mg in patients undergoing knee or hip replacement, as well as in patients with prolonged immobilization during hospitalization, bleeding was observed in approximately 6.8% and 12.6% of patients, respectively, and anemia in approximately 5.9% and 2.1 % of patients respectively. In patients taking Xarelto ® 15 mg twice daily and subsequently switching to 20 mg once daily for the treatment of DVT or PE, or 20 mg for the prevention of recurrent DVT or PE, bleeding was observed in approximately 22.7% of patients, anemia occurred in approximately 2.2% of patients. In patients taking the drug for the prevention of stroke and systemic thromboembolism, the incidence of bleeding of varying severity was 28 per 100 person-years, and anemia - 2.5 per 100 person-years. In patients taking the drug to prevent death due to cardiovascular causes of myocardial infarction in patients after ACS, the incidence of bleeding of varying severity was 22 per 100 person-years, anemia occurred in 1.4 per 100 person-years.

As part of post-marketing surveillance programs, cases of angioedema and allergic edema, the development of which had a temporary relationship with Xarelto, have been reported. It is not possible to estimate the frequency of occurrence of such an undesirable effect within the framework of an observational program. In a randomized phase III clinical trial, such adverse effects were considered infrequent (≥1/1000-≤1/100).

Indications

• prevention of death due to cardiovascular causes and myocardial infarction in patients after acute coronary syndrome (ACS), which occurred with an increase in cardiac-specific biomarkers, in combination therapy with acetylsalicylic acid or with acetylsalicylic acid and thienopyridines - clopidogrel or ticlopidine.

Contraindications

• hypersensitivity to the components of the drug;
• clinically significant active bleeding (eg, intracranial hemorrhage, gastrointestinal bleeding);
• liver diseases occurring with coagulopathy, which causes a clinically significant risk of bleeding, incl. liver cirrhosis and liver dysfunction class B and C according to the Child-Pugh classification;
• pregnancy;
• lactation period (breastfeeding);
• children and adolescents under 18 years of age (efficacy and safety for patients in this age group have not been established);
• clinical data on the use of rivaroxaban in patients with severe renal failure (SC<15 мл/мин) отсутствуют, поэтому применение ривароксабана у данной категории пациентов противопоказано;
• treatment of ACS with antiplatelet agents in patients who have suffered a stroke or transient ischemic attack;
• concomitant therapy with any other anticoagulants, for example, unfractionated heparin, low molecular weight heparins (including enoxaparin, dalteparin), heparin derivatives (including fondaparinux), oral anticoagulants (including warfarin, apixaban, dabigatran ), except when switching from or to rivaroxaban or when using unfractionated heparin in doses necessary to ensure the functioning of a central venous or arterial catheter;
• congenital lactase deficiency, lactose intolerance, glucose-galactose malabsorption (due to the presence of lactose in the drug).

The drug should be used with caution:

• in the treatment of patients with an increased risk of bleeding (including congenital or acquired tendency to bleeding, uncontrolled severe arterial hypertension, peptic ulcer of the stomach and duodenum in the acute phase, recent acute peptic ulcer of the stomach and duodenum, vascular retinopathy, recent history of intracranial or intracerebral hemorrhage, pathology of the spinal cord or brain vessels, after recent surgery on the brain, spinal cord or eyes, bronchiectasis or history of pulmonary hemorrhage);
• in the treatment of patients with moderate renal failure (creatinine clearance 30-49 ml/min) who are simultaneously receiving drugs that increase the concentration of rivaroxaban in the blood plasma;
• when treating patients with severe renal failure (creatinine clearance 15-29 ml/min), caution should be exercised, since the concentration of rivaroxaban in the blood plasma in such patients can increase significantly (on average 1.6 times) and as a result they have an 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 with azole antifungals (eg, ketoconazole) or HIV protease inhibitors (eg, ritonavir). These drugs are strong inhibitors of the CYP3A4 isoenzyme and P-glycoprotein. As a consequence, these drugs may increase plasma concentrations of rivaroxaban to clinically significant levels (average 2.6-fold), which increases the risk of bleeding. Fluconazole (an azole antifungal), a moderate inhibitor of CYP3A4, has a less pronounced effect on the elimination of rivaroxaban and can be used concomitantly with it;
• Patients with severe renal impairment 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 early detection of bleeding complications.

Features of application

Use during pregnancy and breastfeeding

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

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

Due to the possible risk of bleeding and the ability to penetrate the placental barrier, Xarelto ® is contraindicated during pregnancy.

In women of childbearing age, Xarelto should only be used if effective contraception is used.

The effectiveness and safety of Xarelto ® in women during lactation have not been established. Data obtained in experimental animals show that rivaroxaban is excreted in breast milk. Xarelto ® can only be used after breastfeeding has stopped.

Use for liver dysfunction

Use for renal impairment

In patients with mild (creatinine clearance 50-80 ml/min) or moderate (creatinine clearance 30-49 ml/min) renal impairment, no dose adjustment of Xarelto is required.

In patients with severe renal impairment (creatinine clearance 15-29 ml/min), Xarelto should be used with caution, because limited clinical data indicate that plasma concentrations of rivaroxaban are significantly elevated in this patient population. The use of Xarelto ® is contraindicated in patients with CC< 15 мл/мин.

Use in children

Use in elderly patients

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. Thus, these drugs may increase plasma concentrations of rivaroxaban to clinically significant levels (average 2.6-fold), which may lead to an increased risk of bleeding.

However, 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.

There was no effect of Xarelto ® on the duration of the QTc interval.

Kidney failure

Xarelto should be used with caution in patients with moderate renal impairment (creatinine clearance 30-49 ml/min) receiving concomitant medications that may lead to increased plasma concentrations of rivaroxaban.

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 ® следует с осторожностью применять у пациентов с КК 15-29 мл/мин.

Clinical data for patients with severe renal impairment (SKI)<15 мл/мин) не имеется. Поэтому у данной категории пациентов применение препарата Ксарелто ® противопоказано.

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. Monitoring can be carried out by conducting regular physical examinations of patients, carefully monitoring the state of postoperative wound drainage, and also by periodically determining hemoglobin.

Patients with a history of stroke or transient ischemic attack (TIA)

Taking Xarelto ® at a dose of 2.5 mg 2 times a day is contraindicated in patients with ACS who have a history of stroke or TIA. Only a few patients with ACS with a history of stroke or TIA have been studied, so data on the effectiveness of the drug in these patients are extremely limited.

Risk of bleeding

Xarelto ®, like other antithrombotic agents, should be used with caution in diseases and conditions associated with an increased risk of bleeding, such as:

• congenital or acquired coagulation disorders;
• uncontrolled severe arterial hypertension;
• active gastrointestinal pathology with ulceration;
• recent acute ulcer in the gastrointestinal tract;
• vascular retinopathy;
• recent intracranial or intracerebral hemorrhage;
• intraspinal or intracerebral vascular anomalies;
• recent brain, spinal cord, or ophthalmic surgery;
• history of bronchiectasis or episode of pulmonary hemorrhage.

Caution should be exercised if the patient is concomitantly receiving medications that affect hemostasis, such as NSAIDs, platelet aggregation inhibitors, or other antithrombotic drugs.

Patients after ACS receiving Xarelto ® in combination with acetylsalicylic acid or Xarelto ® in combination with acetylsalicylic acid and clopidogrel/ticlopidine should receive NSAIDs as long-term concomitant treatment only if the positive effects of treatment justify the existing risk of bleeding.

Appropriate prophylactic treatment can be used in patients at risk of developing gastrointestinal ulcers.

For any unexplained decrease in hemoglobin or blood pressure, the source of the bleeding must be determined.

The effectiveness and safety of Xarelto ® have been studied in combination with the antiplatelet agent acetylsalicylic acid and clopidogrel/ticlopidine. Use in combination therapy with other antiplatelet agents (for example, prasugrel or ticagrelor) has not been studied and is therefore not recommended for use.

Spinal anesthesia

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 or 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 planned to be prescribed anticoagulants for the purpose of preventing thrombosis. The epidural catheter should be removed no earlier than 18 hours after the last dose of rivaroxaban. Rivaroxaban should be prescribed no earlier than 6 hours after removal of the epidural catheter. In case of traumatic puncture, the administration of rivaroxaban should be postponed for 24 hours.

Surgical operations and interventions

If an invasive procedure or surgery is necessary, Xarelto 2.5 mg should be discontinued at least 24 hours before the procedure, if possible, and based on the clinical judgment of the physician.

If the antiplatelet effect is not required in a patient undergoing elective surgery, the use of platelet aggregation inhibitors should be discontinued as indicated in the manufacturer's prescribing information.

If the procedure cannot be delayed, a comparative assessment of the increased risk of bleeding should be made and the question of whether urgent intervention should be decided.

Xarelto should be restarted after an invasive procedure or surgery as soon as possible, provided clinical indications permit and adequate hemostasis is achieved.

Impact on the ability to drive vehicles and operate machinery

While taking the drug, fainting and dizziness have been reported, which may affect the ability to drive vehicles or use other machinery. Patients who experience such adverse reactions should not drive vehicles or operate machinery.

micronized 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.

Release form

Xarelto is available in film-coated tablets with varying levels of active ingredient. They have a round biconvex shape, pink or red-brown color, double-sided engraving - on one side there is a triangle and a dosage designation, and on the other there is a signature Bayer cross. Packages from 5 to 100 pieces are offered for sale.

pharmachologic effect

Drug that inhibits factor Xa , direct acting anticoagulant .

Pharmacodynamics and pharmacokinetics

For the active substance of this medicine - rivaroxaban , characterized by rapid action, predictable dose-dependent response and high bioavailability. In this case, monitoring of coagulation parameters is not required, and there is virtually no risk of incompatibility with other foods or medications.

The medicine is used as a prophylactic against patients suffering from it, showing good efficacy and tolerability. This anticoagulant can be taken once a day, following a fixed dose.

Rivaroxaban has a high absolute bioavailability of 80–100%. The main component is quickly absorbed with the onset of maximum concentration after 2-4 hours. Once in the body, there is a significant connection of the main part of rivaroxaban with blood plasma proteins, namely plasma albumin . The drug is eliminated mainly in the form of .

Indications for use of the drug Xarelto

The main indications are:

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

Contraindications for use

• active bleeding affecting especially important organs, for example, the gastrointestinal tract, intracranial area, etc.;
• liver diseases accompanied by coagulopathy , causing the risk of bleeding;
• , ;
• patient age less than 18 years;
• congenital lactase deficiency or intolerance, glucose-galactose malabsorption;
• high sensitivity to rivaroxaban and other excipients.

Side effects

Treatment with Xarelto can cause various adverse events affecting almost all organs and systems. However, they often manifest themselves to a moderate degree.

The most common side effects include:

• anemia;
• nausea ,transaminases ,increased GGT activity ;
• hemorrhages after procedures, including postoperative anemia And .

Slightly less common:

• thrombocythemia, increased platelet count;
• , arterial hypotension;
• , pain and discomfort in the abdominal area, dry mouth;
• , short-term loss of consciousness;
• , hematuria, hemorrhage from the genital tract;
• local swelling, deterioration in general health, and so on.

Instructions for Xarelto (Method and dosage)

According to the instructions for use of Xarelto, during the period of VTE prevention after major orthopedic operations, patients are prescribed a daily dose of 10 mg of the drug. The duration of therapy is 2-5 weeks, depending on the scale and complexity of the intervention.

This drug can be taken at any time, regardless of food intake. Treatment with Xarelto should be started 6-10 hours after surgery, if hemostasis. If you miss a dose, you should immediately take Xarelto, and the next day you should continue therapy as usual.

Overdose

In case of overdose rivaroxaban hemorrhagic complications associated with the pharmacodynamic properties of the drug usually develop. Currently rivaroxaban not developed.

To reduce absorption rivaroxaban It is recommended to take it within 8 hours .

Interaction

Simultaneous use of Xarelto with the strongest inhibitors of the isoenzyme CYP3A4 and P-gp can cause a decrease in renal and hepatic clearance, which leads to a significant increase in systemic exposure and pharmacodynamic action of the drug.

Determined that , and can lead to various changes in concentration rivaroxaban , but this is considered to be in the order of normal variability and clinically insignificant.

Concomitant use should be avoided rivaroxaban And dronedarone , since there are no clinical data on this combination.

Taking Xarelto and rifampicin , which refers to the strong CYP3A4 inducers 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.

Terms of sale

The medicine is sold only by prescription.

Storage conditions

The tablets should be stored in a place protected from children, at a temperature below 30 °C.

Best before date

If storage conditions are observed, the drug can be used for 3 years.

Analogues of the drug Xarelto

As is known, analogues of Xarelto are represented only by its active substance or INN Rivaroxaban - direct acting anticoagulant . Therefore, it is believed that this is its main substitute. At the same time, the price of the analog for a package of 14 pieces is 1956-2000 rubles.

Xarelto or Pradaxa- what's better?

This question is asked by many patients who are concerned about the problem of possible blood clots. As recent studies have shown, Xarelto and are almost equally effective in preventing blood clots and risk bleeding at atrial fibrillation . Taking each of these drugs does not require constant INR monitoring. At the same time, the cost of these drugs is quite high compared to other anticoagulants.

Alcohol and Xarelto

Clinical studies have shown that treatment with this drug is strictly incompatible with alcohol consumption, as this can lead to the development of undesirable consequences.

Reviews of Xarelto

Most reviews of Xarelto contain discussions of the risk of active or occult bleeding affecting any tissue or organ, which often leads to anemia of posthemorrhagic nature. At the same time, reviews of patients about Xarelto who took the drug contain information about frequent hemorrhagic complications in the form of: , pallor, swelling and so on.

Also, reviews on forums present vivid discussions about the high cost, which is not affordable for all patients.

Xarelto price, where to buy

This medicine is offered in film-coated tablets with different contents of the active substance. You can buy Xarelto in Moscow at any pharmacy with a doctor's prescription. At the same time, the price of Xarelto 10 mg for 10 pieces per package is from 1226 rubles, the cost of xarelto 20 mg for 14 pieces is from 1564 rubles, and the drug 15 mg for 28 pieces varies from 2857 to 3020 rubles.

If you need to buy these tablets in St. Petersburg, then it should be noted that the price of Xarelto 20 mg is significantly higher than the drug of a lower dosage. Pharmacies in Kyiv offer this medicine at a price of 188 UAH.

• Online pharmacies in Russia Russia
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Xarelto tablets p.p.o. 15 mg 14 pcs. Bayer AG

Xarelto tablets p.p.o. 10 mg 30 pcs. Bayer AG

Xarelto tablets p.p.o. 20 mg 100 pcs. Bayer AG

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Xarelto (tab.p.pl/vol. 15 mg No. 14) Bayer Pharma AG

Xarelto (tab.p.pl/vol.10mg No. 30) Bayer Pharma AG

Xarelto tablets 20 mg No. 28 Bayer Pharma AG

Xarelto (tab.p.pl/vol. 20 mg No. 100) Bayer Pharma AG

Xarelto (tab.p.pl/vol. 10mg No. 100) Bayer Pharma AG

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Xarelto 15 mg 100 tablets Bayer Pharma AG

Xarelto 10 mg 30 tablets Bayer Pharma AG

Xarelto 20 mg 28 tabletsBayer Schering Pharma AG

Xarelto 15 mg 28 tablets Bayer Pharma AG

Xarelto is a direct-acting anticoagulant.

This group of drugs helps suppress blood clotting activity and prevents thrombosis due to reduced fibrin formation.

They affect the biosynthesis of certain elements of the body, allowing changes in blood viscosity, which leads to inhibition of clotting processes. The anticoagulant Xarelto can be used for both therapeutic and prophylactic purposes.

Clinical and pharmacological group

Direct acting anticoagulant.

Conditions for dispensing from pharmacies

Dispensed with a doctor's prescription.

Prices

How much does Xarelto cost? The average price in pharmacies is 1,500 rubles.

Release form and composition

Xarelto is available in the form of tablets coated with a special soluble film coating with a pink-brown or red-brown coating. They are round and have biconvex sides with engraving. At their fracture, a homogeneous white mass is visible, which is surrounded by a colored soluble shell.

1. 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.
2. The film coating of the tablet shell consists of: red iron oxide dye, hypromellose 15cP, titanium dioxide and macrogol 3350.

Packages from 5 to 100 pieces are offered for sale.

Pharmacological effect

The active substance of this drug, rivaroxaban, is characterized by rapid action, a predictable dose-dependent response and high bioavailability. In this case, monitoring of coagulation parameters is not required, and there is virtually no risk of incompatibility with other foods or medications.

Xarelto is used as a preventative against stroke in patients suffering from atrial fibrillation, showing good efficacy and tolerability. This anticoagulant can be taken once a day, following a fixed dose.

Rivaroxaban has a high absolute bioavailability of 80–100%. The main component is quickly absorbed with the onset of maximum concentration after 2-4 hours. Once in the body, there is a significant connection of the main part of rivaroxaban with blood plasma proteins, namely plasma albumin. The drug is excreted primarily in the form of metabolites.

Indications for use

A prophylactic agent for venous thromboembolism in people who have undergone significant surgical interventions on the lower extremities. For orthopedic interventions, the use of 10 mg tablets is recommended.

• Xarelto 15 and 20 mg is used as a prophylactic agent for non-valvular atrial fibrillation. In this case, the drug helps prevent systemic thromboembolism and stroke.

The drug is used to treat deep vein thrombosis and pulmonary embolism and as a prophylactic agent to prevent recurrences of pulmonary embolism and deep venous thromboembolism.

Contraindications

General contraindications for Xarelto tablets:

• Children and adolescents up to 18 years of age;
• Pregnancy;
• Breastfeeding period;
• Hypersensitivity to the components of the drug;
• Liver diseases occurring with coagulopathy, causing a clinically significant risk of bleeding;
• Severe renal failure (creatinine clearance less than 15 ml/min);
• Clinically significant active bleeding (for example, intracranial and gastrointestinal);
• Congenital lactase deficiency, glucose-galactose malabsorption, lactose intolerance;
• Concomitant treatment with any other anticoagulants, for example, oral anticoagulants (dabigatran, warfarin, apixaban), low molecular weight heparins (dalteparin, enoxaparin), unfractionated heparin (UFH), heparin derivatives (fondaparinux); The exception is when a patient is transferred from or to Xarelto therapy, or when low-dose UFH is prescribed to maintain patency of a central venous or arterial catheter.

Contraindications to the use of tablets, depending on the amount of active substance they contain:

• “2.5”: treatment of acute coronary syndrome with antiplatelet agents in patients who have suffered a transient ischemic attack or stroke;
• "10", "15" and "20": injury or condition in which there is an increased risk of major bleeding (eg, aneurysms or vascular pathology of the spinal cord or brain, eye, brain or spinal cord surgery, arteriovenous malformations, recent brain injury or spinal cord, intracranial hemorrhage, suspected or diagnosed esophageal varices, presence of malignant tumors with a high risk of bleeding, recent or existing gastrointestinal ulcer);
• “10”: cases where surgical intervention for a femur fracture is indicated.

Conditions/diseases for which Xarelto tablets are prescribed with caution:

1. Simultaneous use with drugs that affect hemostasis;
2. Severe renal failure (creatinine clearance 15-29 ml/min), due to the possibility of increasing the concentration of rivaroxaban in the blood plasma;
3. Systemic therapy with azole group antifungals or human immunodeficiency virus protease inhibitors, with the exception of fluconazole;
4. Moderate renal failure (creatinine clearance 30-49 ml/min), in which patients receive medications that increase the concentration of rivaroxaban in the blood plasma;
5. Increased risk of bleeding: including bronchiectasis or history of pulmonary hemorrhage, congenital or acquired tendency to bleeding, peptic ulcer of the stomach and duodenum in the acute phase, recent acute peptic ulcer of the stomach and duodenum, vascular retinopathy, uncontrolled severe arterial hypertension, pathology vessels of the spinal cord or brain, recent intracerebral or intracranial hemorrhage, after recent surgery on the eyes, brain or spinal cord).

Use during pregnancy and lactation

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. For women of 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.

Dosage and method of administration

The instructions for use indicate: Xarelto tablets of 10 milligrams are taken regardless of meals, 15 and 20 milligrams are taken with meals.

After major operations on the knee joint, the duration of treatment is two weeks, after major operations on the hip joint - five weeks. The initial dose is taken six to ten hours after surgery if hemostasis is achieved. The therapeutic dose is one tablet per day.

If you miss a dose, take the Xarelto tablet immediately and continue taking the drug regularly the next day as directed. To compensate for a missed dose, doubling the dose taken is prohibited.

Side effects

During the course of drug therapy in patients with hypersensitivity to Rivaroxaban, the following side effects were observed:

1. Hematuria;
2. Hemoptysis, frequent nosebleeds;
3. Peripheral edema;
4. Fever;
5. General weakness, malaise;
6. Possible hemorrhages in the eyeball;
7. Impaired liver function, development of jaundice;
8. Increased level of liver transminase activity;
9. Increased bilirubin concentration;
10. Allergic skin reactions - itching, urticaria, rashes, hemorrhages under the skin;
11. From the hematopoietic system – development of iron deficiency anemia, thrombocytopenia;
12. Headaches, fainting, dizziness, hemorrhages in the brain;
13. From the heart and blood vessels - decreased blood pressure, formation of bruises and hematomas under the skin, in rare cases, tachycardia;
14. From the digestive tract - dyspepsia, flatulence, nausea, dry mouth, bleeding gums, exacerbation of chronic diseases of the digestive canal, risk of gastrointestinal bleeding.

Overdose

In case of an overdose of the drug, no bleeding or other adverse reactions were recorded. With excessive doses (50 mg and above), limited absorption of the drug is possible, leading to the formation of a concentration plateau without a further increase in the average concentration of rivaroxaban in plasma.

If bleeding occurs, it is necessary to postpone the next dose of the drug or cancel treatment for 5–13 hours. Treatment is selected individually, depending on the severity and location of the bleeding. If bleeding cannot be eliminated, specific reverse-acting procoagulant drugs (prothrombin complex concentrate, activated prothrombin complex concentrate, or recombinant factor VIIa) can be used.

special instructions

During the use of the drug, it is important to regularly monitor blood coagulation parameters.

In general, Xarelto does not affect driving ability. In extremely rare cases, undesirable reactions are observed in the form of impaired attention and general malaise, which requires caution.

In elderly patients, the likelihood of bleeding increases while using Xarelto. Therefore, careful dose selection is required.

Before performing surgical operations, it is important to discontinue the use of the drug at least one day before the start.

Drug interactions

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

It has been established that Clarithromycin, Erythromycin and Fluconazole 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 simultaneous use of Xarelto with the strongest inhibitors of the CYP3A4 isoenzyme and P-gp can cause a decrease in renal and hepatic clearance, which leads to a significant increase in systemic exposure and pharmacodynamic action of the drug.

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.