Arikstra

General characteristics. Structure:

Active ingredient: фондапаринукс sodium of 2.5 mg

Excipients: sodium chloride - 4.2 mg, sodium of hydroxide 0.005M of solution / Acidum hydrochloricum 0.01M solution (for maintenance рН 6.0-8.0), water for and - to 0.5 ml.

0.5 ml - syringes glass (5) - pallets plastic (2) - packs cardboard.

Pharmacological properties:

Antitrombotichesky drug. Synthetic selection inhibitor of the activated factor of X (Xa). Antitrombotichesky activity is result of the selection oppression of a factor of Xa mediated by antithrombin III. Selectively contacting antithrombin III, фондапаринукс sodium potentsiirut (approximately by 300 times) initial neutralization of a factor Ha antithrombin III. Neutralization of a factor Ha interrupts a chain of coagulation and inhibits both formation of thrombin, and formation of blood clots. Фондапаринукс sodium does not inactivate thrombin (the activated IIa factor) and does not influence thrombocytes.

At use in a dose of 2.5 mg of Arikstr does not influence results of usual coagulative tests, such as AChTV, the activated time of coagulation (ABC) or prothrombin time / MNO in a blood plasma, on a bleeding time or fibrinolitic activity. However rare messages on lengthening of AChTV at the use of a fondaparinuks in a dosage of 2.5 mg were received.

Фондапаринукс does not give cross-reactions with serum of patients about heparin - the induced thrombocytopenia of the II type.

The pharmacodynamics/pharmacokinetics of a fondaparinuks is defined by its concentration in plasma expressed through anti-Xa - factor activity. It is only possible to apply to calibration assessment of anti-Xa of activity фондапаринукс, the international standard of heparin or low-molecular heparins for this purpose does not approach. Expression of concentration of a fondaparinuks in mg calibration õ«¡ñá»áÓ¿¡Ò¬ßá/litre is result of such calibration.

Pharmacokinetics. Absorption

After п / to introduction фондапаринукс sodium it is completely and quickly absorbed from the place of an injection (absolute bioavailability of 100%). After a single p / to administration of drug in a dose of 2.5 mg to young healthy volunteers of Cmax in a blood plasma it was reached in 2 h after introduction and averaged 0.34 mg/l. The concentration in a blood plasma making a half of the above-stated Cmax were reached in 25 min. after introduction.

At healthy faces of advanced age the pharmacokinetics of a fondaparinuks of sodium is linear in the range of doses of 2-8 mg п / to. At introduction of 1 time / Css it is reached in 3-4 days, at the same time Cmax and AUC values increase by 1.3 times.

In equilibrium state the patients who underwent substitutsionny operations on a hip joint and getting Arikstra п / to in a dose of 2.5 mg/, had average pharmacokinetic parameters of a fondaparinuks of sodium: Cmax - 0.39 mg/l (31%), Tmax - 2.8 h (18%) and Cmin - 0.14 mg/l (56%).

At the patients of advanced age who underwent operations for a change of a hip joint and getting Arikstra in a dose of 2.5 mg/, concentration of a fondaparinuks of sodium in an equilibrium state made: Cssmax - 0.50 mg/l (32%), Cssmin - 0.19 mg/l (58%).

At patients with symptoms is a deep vein thrombosis and the embolism of a pulmonary artery receiving фондапаринукс sodium of 5 mg (at body weight less than 50 kg), 7.5 mg (at body weight from 50 to 100 kg) and 10 mg (at body weight more than 100 kg) п / to 1 time/, were registered similar Cssmax and Cssmin values in plasma at selection of doses according to body weight in all weight categories. Cssmax of drug in a blood plasma varied from 1.2 mg/l to 1:26 mg/l. Average Cssmin in plasma at these patients varied from 0:46 mg/l to 0.62 mg/l.

Distribution

At healthy volunteers фондапаринукс sodium at in/in or п / to introduction, it is generally distributed in blood and only in insignificant degree in intercellular liquid as the seeming Vd in equilibrium state and an unstable state made 7-11 l. In vitro фондапаринукс sodium highly (not less than 94%) specifically contacts ATIII. Linkng of a fondaparinuks of sodium with other proteins of plasma (including with a platelet factor of IV) or erythrocytes slightly.

Metabolism

In vivo metabolism of a fondaparinuks of sodium was not studied since at patients with normal function of kidneys the most part of the entered dose is removed in not changed view with urine.

Removal

Фондапаринукс sodium it is removed by kidneys in not changed look. Healthy people have 64-77% of one dose entered п / to or in/in, is removed with urine during the 72nd p. T1/2 makes about 17 h at young healthy faces and about 21 h - at elderly healthy faces. At patients with normal function of kidneys the average clearance of a fondaparinuks of sodium makes 7.82 ml/min.

Pharmacokinetics in special clinical cases

Patients with a renal failure

At patients removal of a fondaparinuks of sodium happens to a renal failure more slowly since he is generally brought by kidneys in not changed look. At the patients receiving preventive treatment after operations for a fracture of bones of a hip joint or on substitution of a hip joint, the general clearance of a fondaparinuks of sodium is 25% lower at a renal failure of easy degree (KK of 50-80 ml/min.), is 40% lower at a renal failure of moderate degree (KK of 30-50 ml/min.) and 55% below at a renal failure of heavy degree (KK less than 30 ml/min.), in comparison with indicators at patients with normal function of kidneys. Values of final T1/2 made at a renal failure of moderate degree of 29 h, at heavy degree - 72 h. The similar interrelation between clearance of a fondaparinuks of sodium and severity of a renal failure was observed at treatment of patients with a deep vein thrombosis.

Prevention of venous tromboembolic episodes

In pharmacokinetic model data on patients with KK less than 23.5 ml/min. which underwent the lower extremity operations and receiving фондапаринукс sodium were used. As a result of pharmacokinetic modeling it was shown that use of a fondaparinuks of sodium at patients with KK from 20 to 30 ml/min. in a dose of 1.5 mg a day or 2.5 mg every other day corresponds to that at patients with easy and moderate severity of a renal failure (KK of 30-80 ml/min.) receiving drug in a dose of 2.5 mg /

Owing to limitation of the data which are available so far, Arikstra should not be applied at patients with a renal failure of heavy degree.

Patients with an abnormal liver function

It is considered that concentration of a free fondaparinuks of sodium in plasma does not change at easy and average degree of an abnormal liver function therefore on the basis of pharmacokinetics in correction of a dose such patients have no need. After a single p / to introduction of a fondaparinuks of sodium to patients with an abnormal liver function of moderate severity (a functional class B on classification of Chayld-Pyyu), Cmax and AUC decreased by 22-39% in comparison with patients with normal function of a liver. Decrease in concentration of a fondaparinuks of sodium in plasma has a talk reduction of linkng with antithrombin III because of the reduced level of this enzyme in plasma at patients with an abnormal liver function therefore removal of a fondaparinuks of sodium kidneys increases. The pharmacokinetics of a fondaparinuks of sodium at heavy degree of a liver failure was not studied.

Children

Researches on use фондапаринукс sodium at children and teenagers aged up to 17 years were not conducted.

Patients of advanced age

At patients 75 years are aged more senior removal of a fondaparinuks of sodium is slowed down. At introduction of a fondaparinuks of sodium in a dose of 2.5 mg with the preventive purpose after operations for a fracture of bones of a hip joint or on substitution of a hip joint the general clearance of a fondaparinuks of sodium was about 25% less at patients aged 75 years in comparison with patients aged more young are more senior than 65 years. The similar interrelation between clearance of a fondaparinuks of sodium and age was observed at patients with a deep vein thrombosis.

Floor

At dose adjustment according to body weight distinctions in pharmacokinetics depending on a floor were not revealed.

Race

The planned researches of pharmacokinetic distinctions at persons of various race were not conducted. However the tests which were carried out with participation of healthy faces of an Asian origin (Japan) did not reveal distinctions in a pharmacokinetic profile in comparison with that at healthy faces of white race. Distinctions in clearance of drug between the patients of Caucasian and negroid race who underwent orthopedic operations are noted.

Body weight

At patients with body weight less than 50 kg the general clearance of a fondaparinuks of sodium is reduced approximately by 30%.

Indications to use:

— prevention of venous tromboembolic episodes at the patients who are exposed to "big" orthopedic lower extremity operations (a fracture of bones of a hip joint, including long prevention in the postoperative period; operations on substitution of a knee joint; operations on substitution of a hip joint);

— prevention of venous tromboembolic episodes at the patients who are exposed to an abdominal cavity operations and having risks of tromboembolic episodes;

— prevention of venous tromboembolic episodes at patients of a nonsurgical profile with risk factors of such complications in connection with restriction of mobility in the acute period of a disease;

— treatment of an acute deep vein thrombosis;

— treatment of a thromboembolism of a pulmonary artery;

— treatment of an acute coronary syndrome which manifestation is unstable stenocardia or a myocardial infarction without raising of a segment of ST, for the purpose of prevention of cardiovascular death, a myocardial infarction or refractory ischemia;

— treatment of an acute coronary syndrome which manifestation is the myocardial infarction with raising of a segment of ST for the purpose of prevention of death, a repeated myocardial infarction at the patients receiving thrombolytic therapy or the patients who were originally not receiving reperfusion therapy;

— treatment of acute symptomatic thrombosis of superficial veins of the lower extremities without the accompanying deep vein thrombosis.

Route of administration and doses:

Introductions alternately left and right perednebokovy surfaces of a front abdominal wall have to be places п / to. In order to avoid loss of drug it is not necessary to delete vials of air from the syringe. The needle should be entered at all length perpendicularly pleated skin clamped between big and index fingers; the fold of skin is not unclenched during all introduction.

Arikstr's drug is intended for use only under control of the doctor. The patient is allowed to conduct independently п / to an injection only if the doctor considers it necessary, with obligatory subsequent observation at the doctor and only after carrying out the corresponding training in technology of carrying out п / to an injection.

At in introduction (the first dose only at patients at a myocardial infarction with raising of a segment of ST) the drug is administered directly in a catheter or with use of mini-containers from 0.9% chloride sodium solution (25 or 50 ml) in which drug gets divorced previously. In order to avoid loss of drug it is not necessary to delete before an injection vials of air from the syringe. After an injection to wash out a catheter enough normal saline solution, for ensuring delivery of a full dose of drug. At introduction with use of mini-containers infusion has to be carried out by 1-2 min.

Adults

Prevention of venous tromboembolic episodes

Orthopedic and band surgery: the recommended dose of drug of Arikstr makes 2.5 mg п / to 1 time / after operation.

The initial dose is entered not earlier than in 6 h after completion of operation on condition of a well-founded hemostasis.

The course of treatment proceeds during the period of the increased risk of development of venous tromboembolic episodes, usually before transfer of the patient into the out-patient mode, not less than 5-9 days.

Experience shows that for the patients who underwent surgical intervention concerning a fracture of bones of a hip joint, duration of the period of the increased risk of development of venous tromboembolic episodes exceeds 9 days. For such patients it is necessary to make the decision on extension of preventive use of drug of Arikstr up to 24 days.

Patients of a nonsurgical profile with existence of risk factors of tromboembolic episodes: the recommended dose of drug of Arikstr makes 2.5 mg п / to 1 time/Duration of treatment in this case makes from 6 to 14 days.

Treatment of a deep vein thrombosis and thromboembolism of a pulmonary artery

The recommended dose of drug of Arikstr for п / to introduction of 1 times / makes for patients with body weight less than 50 kg - 5 mg; for patients with the body weight of 50-100 kg – 7.5 mg; for patients with body weight more than 100 kg - 10 mg.

Treatment has to continue not less than 5 days and stop not earlier, than full translation on adequate therapy by peroral anticoagulants will be possible, i.e. at achievement of MHO values from 2 to 3. It is necessary to add to treatment antagonists of vitamin K, as a rule, also as soon as possible no later than 72 h. Usually duration of a rate of drug of Arikstr makes from 5 to 9 days.

Treatment of unstable stenocardia / myocardial infarction without raising of a segment of ST

The recommended dose makes 2.5 mg п / to 1 time / Treatment it is necessary to begin as soon as possible after establishment of the diagnosis and to continue within 8 days or to the patient's extract if it occurred earlier, than in 8 days.

If to the patient carrying out ChKV against the background of treatment fondaparinuksy sodium is supposed, during ChKV it is necessary to enter unfractionated heparin (NFG), according to the standard practice accepted in this medical institution; at the same time it is necessary to consider risk of hemorrhagic complications which is available for the patient, and the fact that the level of this risk is influenced including also by time which passed from the moment of introduction of the last dose of a fondaparinuks of sodium.

Time of resuming of administration of drug of Arikstr after removal of a catheter should be defined on the basis of a clinical condition of the patient. In clinical trials treatment fondaparinuksy was resumed not earlier than in 2 h after removal of a catheter.

At the patients who are exposed to aortocoronary shunting (AKSh) at an opportunity фондапаринукс sodium is not entered during 24 h before operation; it is necessary to resume introduction of a fondaparinuks in 48 h after AKSh.

Treatment of a myocardial infarction with raising of a segment of ST

The recommended dose makes 2.5 mg of 1 times / the First dose enter in/in, all the subsequent – п / to. Treatment should be begun as soon as possible after establishment of the diagnosis and to continue within 8 days or to the patient's extract if it occurred earlier, than in 8 days.

If to the patient carrying out not primary ChKV against the background of treatment fondaparinuksy sodium is supposed, during ChKV it is necessary to enter NFG, according to the standard practice accepted in this medical institution; at the same time it is necessary to consider risk of hemorrhagic complications which is available for the patient, and the fact that the level of this risk is influenced including also by time which passed from the moment of introduction of the last dose of a fondaparinuks of sodium.

Time of resuming of administration of drug of Arikstr after removal of a catheter should be defined on the basis of a clinical condition of the patient. In clinical trials treatment fondaparinuksy was resumed not earlier than in 3 h after removal of a catheter.

At the patients who are exposed to AKSh at an opportunity фондапаринукс sodium is not entered during 24 h before operation; it is necessary to resume introduction of a fondaparinuks in 48 h after AKSh.

Treatment of thrombosis of superficial veins

The recommended dose of drug of Arikstr makes 2.5 mg п / to 1 time / Treatment it is necessary to begin as soon as possible after establishment of the diagnosis (without the accompanying deep vein thrombosis) and to continue within 45 days.

Special groups of patients

Children

Pharmacokinetic parameters of a fondaparinuks were characterized in the pharmacokinetic analysis on the basis of data of blood sampling at 24 children. Purpose of 0.1 mg/kg/body weight п / to 1 time / at children is based on the similar exposure of a fondaparinuks observed at adults at introduction of the recommended doses for treatment of a deep vein thrombosis and a thromboembolism of a pulmonary artery.

Patients of advanced age (75 years are more senior)

Arikstr's drug should be used with care at elderly patients since with age depression of function of kidneys is possible. At the elderly patients who underwent surgical intervention it is necessary to observe strictly time of introduction of the first dose of drug of Arikstr.

Patients with body weight less than 50 kg

With body weight less than 50 kg are available for patients risk of development of bleeding. At such patients who underwent surgical intervention it is necessary to observe strictly time of introduction of the first dose of drug of Arikstr.

Patients with a renal failure

Prevention of a venous thromboembolism

For patients with KK more than 30 ml/min. dose adjustment is not required.

Patients with KK have from 20 to 30 ml/min., and also at those patients for whom the advantage of use of a fondaparinuks of sodium exceeds risk of its use, the recommended dosage of drug makes 1.5 mg of 1 times / or on 2.5 mg every other day (i.e. approximately at an interval of 48 h).

At the patients who underwent surgical intervention it is necessary to observe strictly time of introduction of the first dose of drug of Arikstr.

Treatment of a deep vein thrombosis and thromboembolism of a pulmonary artery

For patients with KK of 30 ml/min. and more dose adjustment of drug of Arikstr is not required.

Patients with KK less than 30 ml/min. should not appoint фондапаринукс sodium.

Treatment of unstable stenocardia and myocardial infarction without/with raising of a segment of ST

Use of drug of Arikstr is not recommended for use for patients with KK less than 20 ml/min. Dose adjustment is not required from patients with KK of 20 ml/min. and more.

Treatment of thrombosis of superficial veins

For patients with KK more than 30 ml/min. dose adjustment is not required.

At patients with KK from 30 to 50 ml/min. it is possible to use Arikstr's drug with care.

Patients with KK less than 30 ml/min. should not appoint фондапаринукс sodium.

Patients with an abnormal liver function

For patients with an abnormal liver function easy and moderate severity of correction of doses of drug of Arikstr is not required. Patients with a heavy liver failure should appoint Arikstr's drug with care.

Instruction for drug use

The equipment п / to introduction

1. It is necessary to adopt the provision "sitting" or "lying". To Vyberat the place in the lower part of a stomach, at least 5 cm are lower than a navel.

It is preferable to administer the drug in the right and left parties of a front abdominal wall serially (it will help to reduce discomfort in the place of an injection). Introduction to a hip is allowed.

2. To remove a protective cap, at first having scrolled, and then having pulled it in a straight line from a syringe body. Note: not to touch a needle after removal of a cap and not to allow contact of an open needle with any surfaces. Emergence of vials of air is allowed, it is not necessary to delete them from the syringe before an injection.

3. To hold the syringe strong. The needle should be entered perpendicularly, but not at an angle, at all length the jammed fold of skin who needs to be kept big and index fingers before the end of administration of solution. Then accurately delete a needle. It is not necessary to pound a drug injection site after an injection.

4. After performance of an injection on the used syringe the system of protection is installed: holding the used syringe in one hand for the protective case, other hand to pull for the holder for release of a latch and moving of the case for protection of a needle before the heard click designating a fiuchation of the protective case.

After that the syringe can be subjected to utilization according to an ordinary procedure of removal of medical waste.

Features of use:

Drug Arikstra is intended only for п / to and in/in (a starting dose at patients at a myocardial infarction with raising of a segment of ST) uses. Not to apply in oil!

ChKV and risk of a thrombogenesis in conduction catheters

Use of a fondaparinuks of sodium just before carrying out is not recommended and during primary ChKV at patients at a myocardial infarction with raising of a segment of ST.

Monotherapy fondaparinuksy sodium is not recommended at patients at unstable stenocardia and a myocardial infarction without raising of a segment of ST, at a myocardial infarction with raising of a segment of ST during not primary ChKV; it is necessary to estimate a possibility of the combined purpose of unfractionated heparins.

In clinical trial two modes of dosing of unfractionated heparins are compared during not primary ChKV at unstable stenocardia and a myocardial infarction without raising of a segment of ST at the patients accepting фондапаринукс:

— purpose of a standard dose of unfractionated heparin (average dose of 85 Ekg);

— purpose of a low dose of unfractionated heparin (average dose of 50 Ekg).

Cases of heavy bleedings when carrying out ChKV made 1.2% at purpose of a standard dose of unfractionated heparin and 1.4% at purpose of a low dose of unfractionated heparin.

In controlled researches the risk of catheter thromboses when carrying out ChKV at monotherapy was noted low, but raised in comparison with active control, fondaparinuksy sodium. Frequency of formation of blood clots in conduction catheters at not primary ChKV at patients with unstable stenocardia and a myocardial infarction without raising of a segment of ST made 1% against 0.3% (фондапаринукс sodium in comparison with enoksapariny) and at primary ChKV at patients at a myocardial infarction with raising of a segment of ST - 1.2% against 0% (фондапаринукс sodium in comparison with control).

Cases of formation of blood clots in conduction catheters at not primary ChKV at patients with unstable stenocardia and a myocardial infarction without raising of a segment of ST made 0.1% at purpose of a standard dose of unfractionated heparin and 0.5% at purpose of a low dose of unfractionated heparin.

Prevention venous thromboembolic complication and treatment of venous thromboses and thromboembolism of a pulmonary artery

The drugs increasing risk of development of bleeding should not be appointed together with Arikstr's drug, except for the antagonists of vitamin K used at treatment of venous thromboses and a thromboembolism of a pulmonary artery. In need of use of the combined therapy it should be seen off under strict control.

Prevention of venous tromboembolic episodes after surgical interventions (a starting dose of a fondaparinuks of sodium)

It is necessary to observe strictly time of introduction of the first dose of drug of Arikstr. It has to be entered not earlier than in 6 h after completion of operation, only after a final hemostasis. Purpose of drug of Arikstr earlier, than in 6 h, can be connected with increase in risk of development of heavy bleeding. Patients treat groups of the increased risk 75 years, patients with body weight less than 50 kg, patients with a moderate renal failure are more senior (KK less than 50 ml/min.).

Spinal/epidural anesthesia or lumbar puncture

At use of drug of Arikstr along with carrying out spinal/epidural anesthesia or a lumbar puncture it is impossible to exclude a possibility of emergence of epidural or spinal hematomas which hmonut to lead to long or constant paralysis. The risk of these unusual occurrences can increase at postoperative use of constant epidural catheters or simultaneous administration of other medicines influencing a hemostasis.

Elderly patients

Elderly patients are more subject to risk of bleeding, than other population. As function of kidneys usually decreases with age, at elderly patients removal of a fondaparinuks of sodium can be reduced, and, thus, exposure is increased. Arikstr's drug at elderly patients should be used with care.

Low body weight

Patients with body weight lower than 50 kg are more subject to danger of bleeding. Removal of a fondaparinuks of sodium decreases with decrease in body weight. At such patients Arikstr's drug should be used with care.

Renal failure

About 70% of a fondaparinuks of sodium are removed in not changed look by kidneys. Time of removal of a fondaparinuks of sodium increases with increase in weight of a renal failure and can increase risk of development of bleedings. At patients with a renal failure, especially at KK less than 30 ml/min., the risk of both massive bleedings, and venous tromboembolic episodes increases.

Prevention of venous tromboembolic episodes: clinical data on use of a fondaparinuks of sodium at patients with KK less than 20 ml/min. are insufficient therefore use of a fondaparinuks of sodium for prevention of venous tromboembolic episodes at such patients is not recommended.

Treatment of venous thromboses and thromboembolism of a pulmonary artery: clinical data on use of a fondaparinuks of sodium at patients with KK less than 30 ml/min. are insufficient therefore use of drug of Arikstr for treatment of venous thromboses and a thrombembolia of a pulmonary artery at such patients is not recommended.

Treatment of unstable stenocardia and myocardial infarction without/with raising of a segment of ST: there are limited clinical data on use of a fondaparinuks of sodium for patients at unstable stenocardia and a myocardial infarction without raising of a segment of ST, and at a myocardial infarction with raising of a segment of ST, and KK in the range of 20-30 ml/min. therefore the possibility of use for such patients is estimated from the point of view of a ratio advantage/risk. Фондапаринукс sodium is not recommended to patients with KK less than 20 ml/min.

Heavy abnormal liver functions

Due to the deficit of factors of coagulant system of blood at patients with severe forms of damage of a liver, the risk of bleeding therefore it is necessary to use Arikstr's drug with care increases.

The heparin-induced thrombocytopenia

Effects of a fondaparinuks of sodium are not connected with a platelet factor 4 and do not mention orrhoreactions at patients about heparin - the induced thrombocytopenia of the II type. Arikstr's drug should be used with care at patients about heparin - the induced thrombocytopenia in the anamnesis. So far special clinical trials on studying of efficiency and safety of drug of Arikstr at patients about heparin - the induced thrombocytopenia of the II type were not conducted. Rare messages on development heparin - the induced thrombocytopenia at the patients receiving фондапаринукс sodium were received. To reliable communication between the use of drug and development heparin - the induced thrombocytopenia it is not established.

Allergy to latex

The basis of a needle of the ready graduated syringe may contain dry natural latex which can potentially cause allergic reaction in persons with hypersensitivity to latex.

Influence on ability to driving of motor transport and to control of mechanisms

Researches on studying of influence of drug on ability to drive transport and to work at machines were not conducted.

Side effects:

Frequency of side reactions is presented according to the following gradation: very often (> 1/10), it is frequent (> 1/100, <1/10); sometimes (> 1/1000, <1/100); seldom (> 1/10 000, <1/1000); very seldom (<1/10 000).

These undesirable reactions should be considered in a surgical and therapeutic context depending on indications.

From system of a hemopoiesis: often - anemia, bleeding (various localization, including exceptional cases of intracranial/intracerebral and retroperitoneal bleedings), a purpura; sometimes - thrombocytopenia, a trombotsitemiya, anomaly of thrombocytes, coagulability disturbances.

From a metabolism: seldom - a hypopotassemia.

From a nervous system: sometimes - a headache; seldom - alarm, confusion of consciousness, dizziness, drowsiness, a loss of consciousness.

From cardiovascular system: seldom - arterial hypotension.

From respiratory system: seldom - short wind, cough.

From the alimentary system: sometimes - nausea, vomiting; seldom - abdominal pains, dyspepsia, gastritis, a lock, diarrhea.

From a liver and biliary tract: sometimes - abnormal results of hepatic tests, increase in concentration of enzymes of a liver in blood; seldom - increase in concentration of bilirubin in blood.

From skin and a hypodermic fatty tissue: sometimes - rash, an itch, allocations from a wound.

Others: often - hypostases; sometimes - fever; seldom - infection of a postoperative wound, thorax pain, the lower extremity pain, fatigue, a hyperemia of the person (inflows), syncopal states, allergic reactions, reactions in an injection site.

Interaction with other medicines:

Фондапаринукс sodium does not inhibit isoenzymes of system of P450 cytochrome (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4) of in vitro. Therefore it is not necessary to expect interaction of drug of Arikstr of in vivo with other medicines at the level of suppression of the metabolism mediated by these isoenzymes.

As linkng of a fondaparinuks of sodium with proteins of plasma, except for antithrombin III, slightly, it is not necessary to expect interaction with other medicinal substances at the level of binding sites with proteins of a blood plasma.

In clinical trials of a fondaparinuks of sodium, it was shown that its joint appointment with peroral to anticoagulants and (warfarin), antiagregant (acetylsalicylic acid), NPVS (piroxicam) and cardiac glycosides (digoxin), does not influence pharmacokinetics or a pharmacodynamics of a fondaparinuks of sodium. Фондапаринукс sodium did not influence neither activity of warfarin, nor a bleeding time during treatment by acetylsalicylic acid or piroxicam, pharmacokinetics and a pharmacodynamics of digoxin in an equilibrium state.

Due to the lack of data on compatibility solution of drug of Arikstr should not be mixed with other medicines.

Contraindications:

— active, clinically significant bleeding;

— acute bacterial endocarditis;

— renal failure of heavy degree (KK <20 ml/min.);

— hypersensitivity to a fondaparinuks of sodium or any other component of drug.

It is not recommended to apply фондапаринукс sodium just before and during primary transdermal coronary intervention (ChKV) at patients with a myocardial infarction with raising of a segment of ST.

Monotherapy fondaparinuksy sodium is not recommended at patients with a myocardial infarction without raising of a segment of ST and with raising of a segment of ST at nonprime ChKV. In such cases it is necessary to estimate a possibility of the combined purpose of unfractionated heparins.

The available clinical data on the combined use of a fondaparinuks and unfractionated heparins are limited at nonprime ChKV.

Arikstr's drug, as well as other anticoagulants, it is necessary to apply with care at patients with the increased risk of bleeding, i.e. at such types of pathology as the inborn or acquired disturbances of system of a blood coagulation in the form of bleeding, a peptic ulcer of a stomach and duodenum in stages of an aggravation and recently postponed intracraneal hemorrhages, heavy abnormal liver functions, and also soon after surgical intervention on a head or spinal cord or ophthalmologic operations.

Against the background of use of anticoagulants treat groups of the increased risk of development of bleedings: patients are more senior than 75 years, patients with body weight less than 50 kg, patients with a moderate renal failure (KK less than 50 ml/min.). At Arikstra's appointment care is recommended to the patients carried to risk groups.

At treatment of unstable stenocardia or myocardial infarction without raising of a segment of ST and a myocardial infarction with raising of a segment of ST it is necessary to be careful at the combined use of a fondaparinuks of sodium with other medicines increasing risk of bleeding (for example, GPIIb/IIIa inhibitors or trombolitika).

 

Use of drug ARIKSTRA at pregnancy and feeding by a breast

The data on use of drug of Arikstr for pregnant women which are saved up so far are insufficient therefore it is not necessary to appoint Arikstr's drug pregnant, except for cases when the expected advantage exceeds potential risk for a fruit.

During use of drug of Arikstr feeding the breast does not recommend.

 

Use at abnormal liver functions

Dlyapatsiyentov with an abnormal liver function easy and moderate severity of correction of doses of drug of Arikstr is not required. Patients with a heavy liver failure should appoint Arikstr's drug with care.

 

Use at renal failures

Patients with a renal failure

Prevention of a venous thromboembolism

For patients with KK more than 30 ml/min. dose adjustment is not required.

Patients with KK have from 20 to 30 ml/min., and also at those patients for whom the advantage of use of a fondaparinuks of sodium exceeds risk of its use, the recommended dosage of drug makes 1.5 mg of 1 times / or on 2.5 mg every other day (i.e. approximately at an interval of 48 h).

At the patients who underwent surgical intervention it is necessary to observe strictly time of introduction of the first dose of drug of Arikstr.

Treatment of a deep vein thrombosis and thromboembolism of a pulmonary artery

For patients with KK of 30 ml/min. and more dose adjustment of drug of Arikstr is not required.

Patients with KK less than 30 ml/min. should not appoint фондапаринукс sodium.

Treatment of unstable stenocardia and myocardial infarction without/with raising of a segment of ST

Use of drug of Arikstr is not recommended for use for patients with KK less than 20 ml/min. Dose adjustment is not required from patients with KK of 20 ml/min. and more.

Treatment of thrombosis of superficial veins

For patients with KK more than 30 ml/min. dose adjustment is not required.

At patients with KK from 30 to 50 ml/min. it is possible to use Arikstr's drug with care.

Patients with KK less than 30 ml/min. should not appoint фондапаринукс sodium.

 

Use for elderly patients

Arikstr's drug should be used with care at elderly patients since with age depression of function of kidneys is possible. At the elderly patients who underwent surgical intervention it is necessary to observe strictly time of introduction of the first dose of drug of Arikstr.

 

Use for children

Pharmacokinetic parameters of a fondaparinuks were characterized in the pharmacokinetic analysis on the basis of data of blood sampling at 24 children. Purpose of 0.1 mg/kg/body weight п / to 1 time / at children is based on the similar exposure of a fondaparinuks observed at adults at introduction of the recommended doses for treatment of a deep vein thrombosis and a thromboembolism of a pulmonary artery.

Overdose:

Symptoms: the doses of drug of Arikstr exceeding recommended can lead to increase in risk of bleeding.

Treatment: the overdose complicated by bleeding has to lead to drug withdrawal of Arikstr and to search of primary reason. It is necessary to make the decision on the choice of a method to start the corresponding treatment which can include a surgical hemostasis, completion of blood loss, transfusion of freshly frozen plasma, a plasma exchange.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature not above 25 °C; not to freeze. A period of validity – 3 years.

Issue conditions:

According to the recipe

Packaging:

• solution for in/in and п / to introduction of 2.5 mg / 0.5 ml: syringes 10 - P N015462/01, 18.05.12. Validity period рег. уд. it is not limited.