Arikstra - instructions for use, dose, side effects, contraindications

Active substanceFondaparinux sodiumFondaparinux sodium

Similar drugsTo uncover

solution in / in PC

Dosage form: & nbspsolution for intravenous and subcutaneous administration

Composition:

Name of substance	Number per syringe
Active substance:
Fondaparinux sodium	2.5 mg
Excipients:
Sodium chloride	4.2 mg
Sodium hydroxide	in the form of 0.005 M solution, is used if pH <6
Hydrochloric acid	in the form of a 0.01 M solution, is used if pH> 8
Water for injections	up to 0.5 ml

Description:

Transparent or almost transparent, colorless solution.

Pharmacotherapeutic group:Antithrombotic agent

ATX: & nbsp

B.01.A.X Other anticoagulants

B.01.A.X.05 Fondaparinux sodium

Pharmacodynamics:

Mechanism of action

Fondaparinux sodium is a synthetic and selective inhibitor of activated factor X (Xa). Antithrombotic activity of fondaparinux sodium is the result of selective inhibition of factor Xa, mediated by antithrombin III (AT III). Selectively communicating with AT III, fondaparinux sodium potentiates (approximately 300 times) the initial ability of AT III to neutralize factor X. The neutralization of factor Xa interrupts the coagulation cascade and inhibits both thrombin formation and thrombus formation. Fondaparinux sodium does not inactivate thrombin (activated factor Pa) and does not have an effect on platelets.

Anti-Xa activity. Pharmacodynamics / pharmacokinetics of fondaparinux sodium is determined by its plasma concentrations, expressed through anti-Xa factor activity. For the calibration estimate of anti-Xa activity, only fondaparinux sodium, for this international standard of heparin or low molecular weight heparins does not apply. The result of this calibration is the expression of the concentration of fondaparinux sodium in mg of the fondaparinux calibration / liter.

Pharmacodynamics

In a dose of 2.5 mg fondaparinux sodium does not affect the results of conventional coagulation tests, such as activated partial thromboplastin time (APTT), activated clotting time (ABC) or prothrombin time (PV) / international normalized ratio (INR) in blood plasma, for either bleeding time or fibrinolytic activity. However, spontaneous reports on the prolongation of APTT in the use of fondaparinux sodium in a dosage of 2.5 mg were obtained spontaneously.

Fondaparinux sodium does not cross-react with the serum of patients with heparin-induced thrombocytopenia of type II.

Pharmacokinetics:

Suction

After subcutaneous administration fondaparinux sodium completely and quickly absorbed (absolute bioavailability 100%). With a single subcutaneous injection of 2.5 mg fondaparinux sodium to young healthy volunteers the maximum concentration in blood plasma (mean C_max= 0.34 mg / L) was achieved 2 hours after the dose. Plasma concentrations of half the above maximum concentration were achieved 25 minutes after administration.

In healthy elderly patients, the pharmacokinetics of fondaparinux sodium is linear in the dose range of 2-8 mg subcutaneously. With a single administration per day, the equilibrium concentration in the blood plasma is achieved in 3-4 days with an increase in 1.3 times the values of C_maxand the area under the pharmacokinetic curve "concentration-time" (AUC).

The average pharmacokinetic parameters of sodium fondaparinux in a state of equilibrium in patients who underwent substitution surgery on the hip joint and who received the preparation "Arikstra" subcutaneously at a dose of 2.5 mg per day were: C_max - 0.39 mg / l (31%), t_max- 2.8 hours (18%) and C_max- 0.14 mg / l (56%).In elderly patients who underwent surgery for a hip fracture, the equilibrium concentrations of fondaparinux sodium were: C_max - 0.50 mg / l (32%), C_m_in- 0.19 mg / l (58%).

In patients with symptoms of deep vein thrombosis and pulmonary embolism who received fondaparinux sodium 5 mg (with a body weight of less than 50 kg), 7.5 mg (with a body weight of 50 to 100 kg) and 10 mg (with a body weight of more than 100 kg) subcutaneously once a day; the similar values of the maximum and minimum equilibrium concentrations in plasma were recorded in the selection of doses in accordance with body weight in all weight categories. The maximum equilibrium concentrations of the drug in the blood plasma ranged from 1.20 mg / l to 1.26 mg / l. The mean minimum equilibrium plasma concentrations in these patients ranged from 0.46 mg / L to 0.62 mg / L.

Distribution

In healthy volunteers fondaparinux sodium with intravenous or subcutaneous administration, is mainly distributed in the blood and only to a small extent in the intercellular fluid, since the apparent volume of distribution in a state of equilibrium and unstable state was 7-11 liters. In vitro fondaparinux sodium to a high degree (at least 94%) and specifically binds to antithrombin III (AT III).The binding of fondaparinux sodium to other plasma proteins, including platelet-derived factor IV, or red blood cells is negligible.

Metabolism

In vivo, the metabolism of fondaparinux sodium has not been studied, since most of the administered dose of the drug is excreted unchanged in the urine of patients with normal renal function.

Excretion

Fondaparinux sodium is excreted by the kidneys in an unchanged form. In healthy individuals, 64 to 77% of one dose of the drug administered subcutaneously or intravenously is excreted in the urine within 72 hours. Half-life (T_1/2) is about 17 hours in young healthy individuals, and about 21 hours - in elderly healthy individuals. In patients with normal renal function, the average clearance value of fondaparinux sodium is 7.82 ml / min.

Special groups of patients

Patients with impaired renal function

The induction of fondaparinux sodium is slower in patients with renal insufficiency, since it is mainly excreted by the kidneys unchanged. In patients receiving prophylactic treatment after surgery for a fracture of the hip joint or for hip replacement,the total clearance of fondaparinux sodium is 25% lower than in patients with mild renal insufficiency (creatinine clearance 50-80 ml / min), 40% lower in patients with moderate renal insufficiency (creatinine clearance 30-50 ml / min) and 55% lower in patients with severe renal failure (creatinine clearance less than 30 mL / min) compared with those in patients with normal renal function. The corresponding final half-lives are 29 hours with moderate and 72 hours with severe forms of kidney failure. A similar relationship between the clearance of fondaparinux sodium and the severity of renal failure was observed in the treatment of patients with deep vein thrombosis.

Prevention of venous thromboembolic complications

The pharmacokinetic model used data on patients with creatinine clearance less than 23.5 ml / min, who underwent operations on the lower extremities and received fondaparinux sodium. As a result of pharmacokinetic modeling, it was shown that the use of sodium fondaparinux in patients with creatinine clearance from 20 to 30 ml / min at a dosage of 1.5 mg per day or 2.5 mg every other daycorresponds to that in patients with mild and moderate severity of renal dysfunction (creatinine clearance 30-80 ml / min) receiving 2.5 mg per day.

Due to the limited available data to date, the drug "Arikstra" should not be used in patients with severe renal failure.

Patients with impaired hepatic function

It is believed that the concentration of free fondaparinux sodium in plasma does not change with mild and moderate degree of impaired hepatic function, therefore, based on pharmacokinetics, there is no need to adjust the dose. After a single subcutaneous injection of fondaparinux sodium in patients with impaired liver function of moderate severity (class B in the Child-Pugh classification), C_max and AUC decreased by 22-39% compared with patients with normal liver function. Reducing the concentration of fondaparinux sodium in the plasma is due to a decrease in binding to antithrombin III due to a reduced level of this enzyme in the plasma in patients with impaired liver function, which increases the excretion of fondaparinux sodium by the kidneys.The pharmacokinetics of sodium fondaparinux for severe hepatic insufficiency has not been studied.

Children:

The pharmacokinetic parameters of fondaparinux were characterized in a pharmacokinetic analysis based on blood sampling data from 24 children. The once-daily administration of 0.1 mg / kg subcutaneously in children is based on a similar fondaparinux exposure observed in adults with recommended doses for the treatment of deep vein thrombosis and pulmonary embolism.

Elderly patients

The withdrawal of fondaparinux sodium in patients over the age of 75 years slows down. In a 2.5 mg trial of fondaparinux sodium for prophylaxis after surgery for fracture of the hip joint or for hip replacement, the total clearance of fondaparinux sodium was approximately 25% less in patients over the age of 75 compared with patients at the age of less than 65 years. A similar relationship between the clearance of fondaparinux sodium and age was observed in the treatment of patients with deep vein thrombosis.

Floor

When adjusting the dose by body weight, no differences were found between the sexes.

Race

There were no planned studies of pharmacokinetic differences. However, tests conducted with the participation of healthy people of Asian origin (Japan) showed no differences in the pharmacokinetic profile compared with that of healthy Caucasians. Similarly, there were no differences in the clearance of fondaparinux sodium between patients of the European and Negroid race who underwent orthopedic surgery.

Body mass

In patients with a body weight of less than 50 kg, the total clearance of fondaparinux sodium is reduced by approximately 30%.

Indications:

Prophylaxis - venous thromboembolic complications in patients undergoing "large" orthopedic operations of the lower limbs, such as when:

- fracture of the bones of the hip joint, including long-term prevention in postoperative period;

- surgery for knee replacement the joint;

- surgery for the replacement of the hip the joint.

- Prevention of venous thromboembolic complications in patients undergoing surgery on the abdominal cavity, in the presence of risk factors for thromboembolic complications.

Prevention of venous thromboembolic complications in non-surgical patients in the presence of risk factors for such complications due to the limitation of mobility in the acute period of the disease.

Treatment of deep vein thrombosis.

Treatment of pulmonary embolism with the exception of hemodynamically unstable patients or patients who require thrombolytic therapy or embobectomy.

Treatment of acute coronary syndrome, expressed as: o Unstable angina or myocardial infarction without segment elevation ST in patients who do not have an emergency (within <120 minutes) invasive treatment (percutaneous coronary revascularization), with the goal of preventing cardiovascular death, myocardial infarction or refractory ischemia; o myocardial infarction with segment elevation ST with the aim of preventing death, repeated myocardial infarction in patients receiving thrombolytic therapy or patients who were not initially receiving reperfusion therapy.

- Treatment of acute symptomatic thrombosis of superficial veins of lower limbs without concomitant deep vein thrombosis.

Contraindications:

-Increased sensitivity to fondaparinux sodium or any other component of the drug.

Active clinically significant bleeding.

Acute bacterial endocarditis.

Severe renal insufficiency (creatinine clearance <20ml / min).

Carefully:

It is not recommended to use fondaparinux sodium immediately before and during the primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction.

Monotherapy with fondaparinux sodium is not recommended in patients with myocardial infarction without ST segment elevation and with ST segment elevation in non-primary PCI; should evaluate the possibility of combined appointment unfractionated heparins. The available clinical data on the combined use of fondaparinux sodium and unfractionated heparins in non-primary PCI are limited.

The drug "Arikstra", like other anticoagulants, should be used with caution in patients with an increased risk of bleeding, i.e. with such types of pathology as congenital or acquired disorders of the blood coagulation system in the form of bleeding,gastric ulcer and duodenal ulcer in the acute stage and recently suffered intracranial hemorrhages, severe violations of the liver function, and also soon after surgery on the brain or spinal cord or ophthalmic operations.

The groups of increased risk of bleeding when using anticoagulants include: patients older than 75 years, patients with a body weight of less than 50 kg, patients with moderate renal insufficiency (creatinine clearance less than 50 ml / min). In appointing the drug "Arikstra" patients are assigned to the risk groups, it is recommended to use caution.

In the treatment of unstable angina or myocardial infarction without ST-segment elevation and myocardial infarction with ST-segment elevation, caution should be exercised when combining sodium fondaparinux with other drugs that increase the risk of bleeding (eg GPIIb / IIIa inhibitors or thrombolytic agents).

Pregnancy and lactation:

Data accumulated to date on the use of the drug "Arikstra" in pregnant women are not enough, therefore, the drug "Arikstra" should not be prescribed to pregnant women, except when the expected benefit exceeds the potential risk to the fetus.

During the period of using the drug "Arikstra", breast-feeding is not recommended.

Dosing and Administration:

In places of subcutaneous injection, left and right anterolateral surfaces of the anterior abdominal wall alternate. To avoid loss of the drug should not be before the injection to remove air bubbles from the syringe. The needle should be inserted the entire length perpendicularly into the fold of the skin, sandwiched between the thumb and forefinger; the fold of the skin is not opened during the entire injection.

The drug Arikstra is intended for use only under the supervision of a physician. The patient is allowed to conduct subcutaneous injections himself only if the doctor deems it necessary, with mandatory follow-up by the doctor and only after the appropriate training in the technique of subcutaneous injection. Intravenous administration (first dose only in patients with myocardial infarction with ST segment elevation).

A drug Arikstra is administered directly to the catheter or using mini-containers with 0.9% sodium chloride solution (25 or 50 ml), in which the drug is previously diluted.When using Arikstra in syringes, do not remove air bubbles from the syringe before injecting to avoid loss of the drug. After injection, the catheter should be rinsed with a sufficient amount of 0.9% solution to ensure delivery of the full dose of the drug. When administered with the use of mini-containers, the infusion should be performed within 1-2 minutes.

Adults

Prevention venous thromboembolic complications

Orthopedic and cavitary surgery

The recommended dose of Arikstra is 2.5 mg subcutaneously once a day after surgery.

The initial dose is administered no earlier than 6 hours after the end of the operation, provided that the hemostasis is consistent.

The course of treatment should continue during a period of increased risk of venous thromboembolic complications, usually before transferring the patient to an outpatient schedule, for at least 5-9 days. Experience shows that for patients who have undergone surgical intervention for a fracture of the bones of the hip joint, the duration of the period of increased risk development of venous thromboembolic complications exceed 9 days after surgery.For such patients, a decision must be made to extend the prophylactic use of Arikstra to 24 days.

Non-surgical patients with factors risk of thromboembolic complications

The recommended dose of Arikstra is 2.5 mg subcutaneously once a day. The duration of treatment in this case is from 6 to 14 days.

Treatment of deep vein thrombosis and pulmonary embolism

The recommended dose of Arikstra in the form of a subcutaneous injection once a day is:

-5 mg for patients with body weight less than 50 kg;

-7.5 mg for patients with a body weight of 50-100 kg;

-10 mg for patients with a body weight of more than 100 kg.

Treatment should last at least 5 days and stop no earlier than a full transfer to adequate therapy with oral anticoagulants will be possible, i.e. when the values of the international of a normalized ratio (INR) of 2 to 3. To add vitamin K antagonists to therapy as soon as possible, as rule, no later than 72 hours. Usually drug course duration Arikstra is from 5 to 9 days.

Treatment of unstable angina or myocardial infarction without segment elevation ST

The recommended dose of Arikstra is 2.5 mg subcutaneously once a day. Treatment should be started as soon as possible faster after diagnosis and continue for 8 days or until patient discharge from the hospital, If she occurred earlier than in 8 days. If the patient is supposed to PCI on the background of drug treatment Arikstra, during PCI should be administered unfractionated heparin (UFH), according to standard practice adopted in the given medical institution; wherein it is necessary to take into account the risk of bleeding, which is available patient, and what is at the level of this risk influences, among other things, the time elapsed since the moment of the last dose preparation of Arikstra.

Time of resumption of drug administration Arikstra after removal of the catheter must determined on the basis of clinical patient's condition. In clinical drug treatment studies Arikstra was renewed no earlier than 2 hours after catheter removal.

Have patients, subject to coronary artery bypass grafting (CABG), if possible, Arikstra is not injected within 24 hours before surgery. The administration of Arikstra can be resumed 48 hours after CABG.

Treatment of myocardial infarction with ST segment elevation

The recommended dose of Arikstra is 2.5 mg once a day. The first dose of the drug is administered intravenously, subsequent doses are administered subcutaneously. Treatment should begin as soon as possible after diagnosis and continue for 8 days or until discharge from the hospital if it occurred earlier than 8 days later.

If the patient is expected to have a non-primary PCI on the background of treatment with Arikstra, PCI should be administered during the course of PCI, according to the standard practice adopted in this clinic; it is necessary to take into account the risk of bleeding that the patient has, and the fact that the level of this risk is affected, in part, by the time elapsed since the last dose of the drug was administered.

The time to resume administration of Arikstra after removal of the catheter should be determined based on the clinical condition of the patient. In clinical trials, treatment with Arikstra was resumed no earlier than 3 hours after removal of the catheter.

In patients undergoing CABG, if possible, Arikstra is not injected within 24 hours before surgery.The administration of the drug can be resumed 48 hours after CABG.

Treatment of venous thrombosis The recommended dose of Arikstra is 2.5 mg subcutaneously once a day. Indication for the use of the drug Arikstra in a dose of 2.5 mg is acute, symptomatic, isolated, spontaneous thrombosis of superficial veins of the lower extremities, at which extent of the affected section is not less than 5 cm, and the corresponding lesion was documented on the basis of the results of ultrasound or other objective methods. Treatment should be started as soon as possible faster after diagnosis and after exclusion of concomitant deep vein thrombosis or thrombosis superficial veins length of no more than 3 cm from the saphenofemoral anastomosis. Have patients with a high risk of thromboembolic complications duration of treatment must be at least 30 and not more than 45 days. The patient is allowed self-administered subcutaneous injections, only if the doctor deems it necessary, with mandatory follow-up care by the doctor and only after holding appropriate training in the technique of subcutaneous injection.

- Patients in need of surgery or other invasive procedures. Patients from thrombosis surface veins in need of surgery or other invasive procedures should not, if possible, receive fondaparinux for at least 24 hours before the surgical operation.

The use of fondaparinux can be resumed at least 6 hours after hemostasis is restored.

Special patient groups

Children

The use of Arikstra is not recommended in children younger than 17 years due to lack of data on efficacy and safety.

Patients elderly (over 75 years)

The drug Arikstra should be used with ankleiness in elderly patients, because with age, the kidney function decreases. In elderly patients undergoing surgery, It is necessary to strictly observe the time of administration of the first dose of Arikstra.

Patients with low body weight

Prophylaxis of venous thromboembolism and treatment of unstable angina or myocardial infarction without or with ST segment elevation

Patients weighing less than 50 kg have an increased risk of bleeding. The rate of withdrawal of fondaparinux decreases with decrease in body weight. The drug Arikstra should be used with the sensitivity of this group of patients.

Treatment of venous thrombosis

Efficiency and security The use of Arikstra in patients with a body weight of less than 50 kg has not been studied, and therefore its use in such patients is not recommended.

Patients with impaired renal function

Prevention of venous thromboembolism

Do not administer Arikstra to patients with creatinine clearance less than 20 mL / min. If the creatinine clearance is 20 to 50 ml / min, the dose should be reduced to 1.5 mg once daily. With mild renal impairment (creatinine clearance more than 50 ml / min), a dose reduction is not required.

Treatment of unstable angina or myocardial infarction without or with ST segment elevation

The use of Arikstra is not recommended for use in patients with creatinine clearance less than 20 ml / min. Dose adjustments are not required in patients with creatinine clearance greater than 20 mL / min.

Treatment of venous thrombosis

Do not administer Arikstra to patients with creatinine clearance less than 20 mL / min. If creatinine clearance is 20 to 50 ml / min, the dose should be reduced to 1.5 mg once daily. With mild renal impairment (creatinine clearance more than 50 ml / min), a dose reduction is not required. The safety and efficacy of this drug at a dose of 1.5 mg have not been studied.

Patients with impaired hepatic function

Prophylaxis of venous thromboembolism and treatment of unstable angina or myocardial infarction without or with ST segment elevation

For patients with a mild or moderate liver function disorder, correction of the dose of Arikstra is not required. Patients with severe hepatic insufficiency Arikstra should be administered with caution, since the use of this drug in this group of patients has not been studied.

Treatment of venous thrombosis

The effectiveness and safety of the use of Arikstra in patients with severe hepatic impairment have not been studied, therefore, the use of the drug in this group of patients is not recommended.

INSTRUCTION FOR USE

1. Needle guard.

2. Piston.

3.Holder.

4. Protective housing.

The technique of subcutaneous injection

1. The "sitting" or "lying" position should be adopted.

Choose a place in the lower abdomen, at least 5 cm below the navel.

Preferably, the drug is administered to the right and left sides of the anterior abdominal wall in turn (this will help reduce discomfort at the injection site). Admission to the hip is permissible.

2. Remove the protective cap by first scrolling and then pulling it in a straight line from the body of the syringe.

Note: do not touch the needle after removing the cap and do not allow the exposed needle to contact any surfaces. Air bubbles are allowed, do not remove them from the syringe before injection.

3. Hold the syringe tightly. The needle should be inserted perpendicularly, and not at an angle, for the entire length into the pinched skin fold, which must be held with the thumb and forefinger until the end of the solution. Then gently remove the needle. Do not rub the injection site after injection.

4. After the injection, the following protection system is installed on the used syringe:

holding the used syringe in one hand for the protective case,the other hand is pulled by the holder to release the latch and slide the body to protect the needle until an audible click indicates the fixation of the protective housing.

After that, the syringe can be disposed of in accordance with the usual procedure for the disposal of medical waste.

Side effects:

Unwanted reactions presented below are listed in accordance with damage to organs and systems of organs and frequency of occurrence. Frequency is determined by the following way: very often (≥1/10), often (≥ 1/100 and <1/10), infrequently (≥ 1/1 000 and <1/100), rarely (≥ 1/10 000 and <1/1 000), very rarely (< 1/10 000).

These undesirable effects follow treated in the surgical and therapeutic context in relation to from the testimony.

Infectious and parasitic diseases

Rarely: infection postoperative wound.

Violations from the blood and lymphatic system

Often: anemia, bleeding (different localization, including rare cases intracranial and / or intracerebral and retroperitoneal hemorrhages and / or bleeding), purpura.

Infrequently: thrombocytopenia, thrombocythemia, anomaly thrombocytes, disorders coagulability.

Violations from the immune systems

Rarely: allergic reactions (including very rare reports on angioedema, anaphylactoid and / or anaphylactic reactions).

Disorders from the metabolism and supply

Rarely: hypokalemia.

Disturbances from the nervous system

Infrequently: headache.

Rarely: anxiety, confusion consciousness, dizziness, spatial disorientation, drowsiness.

Vascular disorders

Rarely: arterial hypotension.

Violations from the respiratory system, chest organs and the mediastinum

Rarely: shortness of breath, cough.

Disorders from the gastro-intestinal tract

Infrequently: nausea, vomiting.

Rarely: abdominal pain, indigestion, gastritis, constipation, diarrhea.

Disorders from the liver and bile ducts

Infrequently: abnormal results hepatic enzyme concentrations liver in the blood.

Rarely: increase in concentration bilirubin in the blood.

Disturbances from the skin and subcutaneous tissue

Infrequently: rash, itching, discharge from the wound.

General disorders and disorders in place of introduction

Often: edema.

Infrequently: fever, peripheral edema.

Rarely: reactions at the injection site, pain in the chest, pain in the chest lower limbs, fatigue, hyperemia of the face (tides), syncopal conditions, swelling of the genitals.

Overdose:

Symptoms

Doses of "Arikstra", exceeding the recommended ones, can lead to an increased risk of bleeding.

Treatment

An overdose complicated by bleeding should lead to the cancellation of the drug "Arikstra" and to the search for a primary cause. To decide on the choice of method for starting the appropriate treatment, which may include surgical hemostasis, supplementation of blood loss, transfusion of fresh frozen plasma, plasmapheresis.

Interaction:

Fondaparinux sodium group does not inhibit isozymes of cytochrome P450 (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4) in vitro. Consequently, one should not expect drug interactions "Arikstra" in vivo with other drugs to suppress the level of metabolism mediated CYP system. Since the binding of fondaparinux sodium to plasma proteins, except ATSH slightly, one should not expect interactions with other drugs at the level of competitive binding to plasma proteins.

In clinical studies of fondaparinux sodium, it has been shown that its co-administration with oral anticoagulants (warfarin), antiaggregants (acetylsalicylic acid), nonsteroidal anti-inflammatory drugs (piroxicam) and cardiac glycosides (digoxin), does not affect the pharmacokinetics or pharmacodynamics of fondaparinux sodium. Fondaparinux sodium did not affect the activity of warfarin, nor during bleeding during treatment with acetylsalicylic acid or piroxicam, nor on the pharmacokinetics and pharmacodynamics of digoxin in the equilibrium state.

Due to the lack of compatibility data, the solution of the drug "Arikstra" should not be mixed with other drugs.

Special instructions:

The drug Arikstra is intended only for subcutaneous and intravenous administration. Do not use intramuscularly!

Bleeding

Fondaparinux should be used with caution in patients with an increased risk of bleeding due to hereditary or acquired coagulation disorders (eg, platelets less than 50,000 / mm³), diseases of the gastrointestinal tract with ulcers in the active phase, recent intracranial hemorrhage or surgery on the brain, spinal cord or vision organs, as well as in special groups of patients, as described below.

Do not use drugs with fondaparinux to prevent venous thromboembolic complications, which increase the risk of bleeding. These drugs include desandin, fibrinolytic agents, antagonists of glycoprotein IIb / IIIa receptors of platelets, heparin, heparinoids or low molecular weight heparin. If necessary, it is possible to conduct concomitant therapy with a vitamin K antagonist. Other antiplatelet drugs (acetylsalicylic acid, dipyridamole, sulfinpyrazone, ticlopidine or clopidogrel) and non-steroidal anti-inflammatory drugs should be used with caution. If absolutely necessary, the concomitant use of such drugs requires careful monitoring of the patient.

PCI and risk of thrombus formation in the conductor catheters Fondaparinux is not recommendedimmediately before and during primary PCI in patients with myocardial infarction with ST segment elevation. Similarly, in patients with unstable angina pectoris or myocardial infarction without ST segment elevation in life-threatening situations that necessitate an emergency revascularization, it is not recommended to apply fondaparinux before and during PCI. These are patients with refractory or recurrent angina associated with the dynamic deviation of the segment ST, heart failure, life-threatening arrhythmias or hemodynamic instability.

Monotherapy with fondaparinux is not recommended in patients with unstable angina or myocardial infarction without ST-segment elevation and with myocardial infarction with ST-segment elevation during non-primary PCI because of increased risk of blood clots in the conductor catheters. Therefore, according to the standard practice of treatment, the possibility of combined administration of UFH should be assessed.

Thrombosis of superficial veins

It should be excluded concomitant thrombosis of deep veins or thrombosis of superficial veins,at which the affected area is localized for no more than 3 cm from the saphenofemoral anastasia, as the use of the Arikstra preparation in a dose of 2.5 mg has not been studied in the presence of the above diagnoses.

The efficacy and safety of fondaparinux 2.5 mg has not been studied in the following patient groups: patients with surface vein thrombosis after sclerotherapy or complications in the intravenous bed, patients with a history of previous vein thrombosis in the previous 3 months, patients with previous history of thromboembolic complications 6 months or patients with an active malignant tumor.

Spinal / epidural anesthesia

With the use of the preparation of Arikstra, simultaneous with spinal / epidural anesthesia or lumbar puncture, the possibility of epidural or spinal hematomas, which can lead to prolonged or permanent paralysis, can not be ruled out during "large" orthopedic operations. The risk of these rare events may increase with postoperative use of permanent epidural catheters or simultaneous administration of other drugs that affect hemostasis.

Elderly patients

Older patients are more at risk of bleeding than the rest of the population. Since the kidney function usually decreases with age, the withdrawal of fondaparinux in older patients can be reduced, and thus the exposure is increased. Arikstra should be used with caution in elderly patients.

Low body weight

Prevention venous thromboembolic complications and treatment of unstable angina or myocardial infarction without or with ST segment elevation

Patients weighing less than 50 kg have an increased risk of bleeding. The rate of withdrawal of fondaparinux decreases with decreasing body weight. The drug Arikstra should be used with the sensitivity of this group of patients.

Treatment of venous thrombosis

There is insufficient clinical data on the use of fondaparinux in patients weighing less than 50 kg, so its use in such patients is not recommended.

Impaired renal function

Fondaparinux, in general, is excreted by the kidneys.

Prevention venous thromboembolic complications

In patients with creatinine clearance less than 50 ml / min, the risk of bleeding increases and venous thromboembolic complications, therefore fondaparinux should be used with caution. There is insufficient clinical data on the use of fondaparinux in patients with creatinine clearance less than 30 ml / min.

Treatment of unstable angina or myocardial infarction without or with ST segment elevation

There are limited clinical data on the use of fondaparinux in patients with unstable angina or myocardial infarction without ST-segment elevation, and in ST-elevation myocardial infarction and creatinine clearance in the range of 20-30 ml / min, therefore, the possibility of use in such patients is assessed with terms of the ratio of expected benefits to possible risks.

Treatment of venous thrombosis

Fondaparinux is not recommended for patients with creatinine clearance less than 20 mL / min. In patients with creatinine clearance in the range of 20-50 ml / min, the dose should be reduced to 1.5 mg once daily. The efficacy and safety of a dose of 1.5 mg have not been studied.

Severe hepatic impairment

Prevention venous thromboembolic complications and treatment of unstable angina or myocardial infarction without or with ST segment elevation

Correction of dose when used in this group of patients is not required. However, due to the deficiency of coagulation factors in patients with severe forms of liver damage, the risk of bleeding increases, so use Arikstra such patients should be treated with caution.

Treatment of thrombosis of superficial veins

There is insufficient data on the use of fondaparinux in this group patients. Therefore, its use in of this group of patients recommended.

Heparin-induced thrombocytopenia

Aricstra should be used with caution patients with heparin-induced thrombocytopenia in the anamnesis. Until now, not Special clinical studies were conducted on the study of efficacy and safety of Arikstra patients with heparin-induced thrombocytopenia type II. Were received rare reports of development heparin-induced thrombocytopenia in patients who received fondaparinux.Fondaparinux does not bind to the 4 th platelet factor and does not have cross-reactive serum reactions in patients with heparin-induced thrombocytopenia of type II A reliable relationship between drug use and the development of heparin-induced thrombocytopenia has not been established.

Allergy to latex

The base of the needle of the finished graduated syringe may contain dry natural latex, which can potentially cause an allergic reaction in persons with hypersensitivity to latex.

Effect on the ability to drive transp. cf. and fur:

Studies to study the effect of the drug on the ability to drive transport and work on machines were not conducted.

Form release / dosage:

Solution for subcutaneous and intravenous administration 2.5 mg / 0.5 ml.

Packaging:

For 0.5 ml of the preparation in a syringe of neutral glass type I with a capacity of 1 ml, connected to the needle and closed with a plug-in screw made of chlorobutyl elastomer, equipped with an automatic safety system.

5 syringes per plastic pallet. 2 pallets in a cardboard box together with instructions for medical use.

Storage conditions:

Store at a temperature not exceeding 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the product after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N 015462/01

Date of registration:15.12.2008 / 02.02.2015

Expiration Date:Unlimited

The owner of the registration certificate:Aspen Pharma Trading LimitedAspen Pharma Trading Limited