Флюксум®

General characteristics. Structure:

Active ingredient: 3200/4250/6400 Anti-ha ME of a parnaparin of sodium.

Excipients: water for injections.

Pharmacological properties:

Pharmacodynamics. Флюксум® contains active ingredient парнапарин sodium, low-molecular гликозаминогликан with a molecular weight from 4000 to 6000 Da (average molecular weight about 5000 Yes) which is received in the course of a depolymerization of the heparin emitted from a mucous membrane of a small intestine of a pig.

Parnaparin of sodium possesses antitrombotichesky action. In vitro and in vivo it suppresses substantially a factor Ha, exerts small impact on a factor of II and and on the partial activated tromboplastinovy time (AChTV). Antitrombotichesky activity (Anti-ha) of drug exceeds anti-coagulative (Anti-Pa). So, the relation Anti-ha / анти-Па activities from 1,5 to 3 (in comparison with heparin for which this ratio is equal to 1). Parnaparin of sodium does not possess proagregantny platelet action.

Pharmacokinetics. Pharmacokinetics of a parnaparin of sodium linear in the range of doses from 3200 Anti-ha ME to 12800 Anti-ha ME. After hypodermic (п / to) introductions of a single dose the maximum antikha activity in plasma is created in 2 - 3 hours. Then decrease of the activity which, however, in 12 hours after introduction of a dose still is defined is observed. Elimination half-life about 6 hours. At repeated dosing the steady condition of pharmacokinetics is observed for the 3rd day at use of drug in a dose 3200 Anti-ha of ME 2 times a day and for the 4th day at use in a dose 6400 Anti-ha of ME once a day.

Bioavailability of a parnaparin of sodium which is estimated on Anti-ha activity is close to 100%. The area under a curve "concentration - time" (AUC) has linear dependence on a dose. At a hypodermic way of introduction the pharmacokinetic profile a-Ha activities is more favorable in comparison with a profile at intravenous administration as it is characterized by smoother curve with existence of smaller number of peaks and slower decrease of the activity. Parnaparin of sodium is distributed in a liver and kidneys. In a liver it is metabolized before inactive connections and brought out of an organism through kidneys.

Indications to use:

Prevention of the deep vein thrombosis (DVT):
• at all-surgical and orthopedic operations
• patients with high risk have development of a deep vein thrombosis.

Treatment of a deep vein thrombosis, posttromboflebitichesky syndrome, chronic venous insufficiency, acute thrombophlebitis of superficial veins, varicophlebitis

Route of administration and doses:

Флюксум® enter into hypodermic cellulose of a stomach, into thickness of a skin fold. The needle is located perpendicular to a fold, between big and index fingers. The skin fold keeps until the end of an injection. The place of an injection needs to be changed.

Prevention of TGV in the general and orthopedic surgery and at patients with the increased risk of TGV

General surgery. 0,3 ml (3200 anti-Ha ME) in 2 hours prior to operation. Then 1 times/days within not less than 7 days.

Orthopedic surgery and at patients with the increased risk of TGV. 0,4 ml (4250 anti-Ha ME) in 12 hours prior to operation, then 1 time/day during the postoperative period, not less than 10 days.

Treatment. TGV. 0,6 ml (6400 Anti-ha ME) 2 times a day within not less than 7-10 days. If necessary treatment it is possible to begin with slow infusional introduction 1,2 ml (12800 Anti-ha of ME) within 3-5 days. After stopping of an acute phase of a disease it is recommended to continue п / to administration of drug in a dose of 0,6 ml (6400 Anti-ha of ME) or 0,4 ml (4250 Anti-ha of ME) within 10-20 days.

Posttromboflebitichesky syndrome and chronic venous insufficiency. On 0,6 ml (6400 Anti-ha ME) or 0,4 ml (4250 Anti-ha ME) or 0,3 ml (3200 Anti-ha ME) depending on disease severity once a day within not less than 30 days.

Acute thrombophlebitis of superficial veins, varicophlebitis. On 0,6 ml (6400 Anti-ha ME) or 0,4 ml (4250 Anti-ha ME) or 0,3 ml (3200 Anti-ha ME) depending on disease severity once a day within not less than 20 days.

Features of use:

Use at pregnancy and a lactation. The conducted researches on animals did not show teratogenic and embriotoksichesky action of a parnaparin of sodium. There are no convincing data on penetration through a placental barrier and about excretion in breast milk.

However, as completely it is impossible to exclude risk of toxic influence of a parnaparin of sodium on a fruit, at pregnancy drug should be accepted only in urgent cases and under direct observation of the doctor. In need of use of drug in the period of a lactation, breastfeeding should be stopped.

Флюксум® it is impossible to enter intramusculary.

The thrombocytopenia induced by heparin. It is known that Flyuksum® as heparin and other low-molecular heparins, can cause thrombocytopenia. Geparinindutsirovanny thrombocytopenia usually develops in 4-10 days from an initiation of treatment or earlier at repeated cases. Early slight thrombocytopenia (thrombocytes> 100000/mkl) which can remain or regress at treatment continuation occurs at 10-20% of patients. As a result of antibody formation to a complex heparin / the platelet factor 4 in certain cases can develop more severe immune form, geparinindutsirovanny thrombocytopenia of the II type, with the subsequent thrombogenesis and a thromboembolism in arteries of a brain, lungs, the lower extremities, etc. is frequent with a lethal outcome. During treatment of patients by Flyuksum it is necessary to observe carefully.

At prolonged treatment the number of thrombocytes should be defined before therapy by Flyuksum and 2 times a week within the first month, and then monitoring of number of thrombocytes can be more rare. With extra care it is necessary to appoint Flyuksum® to patients in whose anamnesis there are data on the thrombocytopenia caused by heparin or other low-molecular heparin, calculation of number of thrombocytes at them needs to be made every day. If thrombocytopenia arises during treatment by heparin, then therapy by low-molecular heparins can be an alternative method of treatment. At the same time the number of thrombocytes should be defined daily and if thrombocytopenia remains, then low-molecular heparin needs to be cancelled as soon as possible.

At thrombocytopenia less 100000/mkl, at emergence and progressing of thrombosis Flyuksum® it is necessary to cancel and transfer the patient to other anticoagulating therapy. Switching to therapy by peroral anticoagulants in these cases is not recommended as it is known of progressing of thrombosis.

At suspicion of geparinindutsirovanny thrombocytopenia tests for aggregation of thrombocytes of in vitro have no great diagnostic value, consultation of specialists is necessary.

Spinal/epidural anesthesia. Carrying out spinal or epidural anesthesia, a spinal and epidural analgesia or lumbar puncture against the background of preventive use of Flyuksum, as well as other low-molecular heparins, can be complicated by a spinal or epidural hematoma with development of persistent or irreversible paralysis. The risk of these complications increases when using epidural catheters, at reception of the accompanying NPVP. antiagregantny medicines or anticoagulants, at an injury or repeated spinal punctures, existence of initial disturbances of a hemostasis or at patients of advanced age. In need of carrying out an anesthesia/analgesia of this kind against the background of preventive use of Flyuksum it is necessary to check carefully existence of the specified risk factors before these interventions.

Usually spinal catheters establish not earlier than 8-12 hours after the last introduction of a preventive dose of low-molecular heparin. It is impossible to enter Flyuksum® in 2 - 4 hours prior to establishment/removal of a catheter. The injection has to be detained or cancelled if blood from the spinal channel when carrying out spinal or epidural anesthesia is aspirated. The catheter should be removed as it is possible later after (in 8-12 hours) the last preventive introduction of Flyuksum.

It is necessary to pay special attention to patients who received Flyuksum® to or after epidural or spinal anesthesia, checking existence of neurologic symptoms, such as a back pain, sensitive and motive frustration (numbness or weakness in the lower extremities), dysfunction of intestines or bladder. Patients should be informed on need of the immediate address to the doctor at emergence of the specified symptoms. At suspicion of an epidural or spinal hematoma immediate diagnosis and treatment, including a decompression of a spinal cord is required.

Low-molecular heparins differ from each other on the molecular weight and specific activity, doses therefore it is not recommended to alternate Flyuksum's use to other low-molecular heparins in the course of treatment.

At emergence of a necrosis of skin treatment by Flyuksum needs to be interrupted.

Influence on ability to manage motor transport. Флюксум® does not exert impact on ability to manage motor transport and to be engaged in the types of activity requiring special attention and speed of psychomotor reactions.

Side effects:

Thrombocytopenia cases, allergic reactions, hematoma and necrosis of skin in the place of an injection are sometimes observed.

The purpura or the erythematic painful centers with or without the general symptoms can precede a necrosis of skin. Increase in activity of "hepatic" transaminases can be observed.

In isolated cases the spinal or epidural hematoma connected with preventive use of drug during a spinal, epidural and lumbar puncture meets.

The hematoma causes varying severity neurologic disturbances, including persistent or irreversible paralysis.

Interaction with other medicines:

Medicinal combinations which are not recommended:

Acetylsalicylic acid, other salicylates, NPVP: the risk of bleeding because of antithrombocytic effect and the damaging influence on a mucous membrane of digestive tract of these drugs is increased.

Tiklopidin: the risk of bleeding because of antithrombocytic action is increased.
Combined use with high therapeutic doses of a parnaparin of sodium is not recommended. At use together with low preventive doses of a parnaparin of sodium, careful clinical observation and control of coagulation indicators is necessary.

Other antiagregantny medicines (for example, klopidogret, Dipiridamolum): the risk of bleeding is increased.

Sulfinpyrazonum: the risk of bleeding is increased.

Medicinal combinations which can be applied with care:

Peroral anticoagulants: strengthening of anti-coagulative action. When replacing a parnaparin of sodium with peroral anticoagulants careful observation of the patient is necessary. To estimate influence of these drugs on a hemostasis, blood tests should be taken before purpose of a parnaparin of sodium.

System GKS: the risk of bleeding at reception of GKS in high doses is increased more than 10 days because of injury of a mucous membrane of a gastro intestinal path and direct impact on a wall of vessels.

Use of a parnaparin of sodium together with GKS it is necessary to prove and carry out this therapy under observation of the doctor.

Dextran (for parenteral use): the risk of bleeding because of antithrombocytic action is increased. At combined use dose adjustment of a parnaparin of sodium that decrease in indicators of a blood coagulation was no more, than by 1,5 times is necessary.

The effect of a parnaparin of sodium decreases at combined use with ascorbic acid, antihistaminic drugs, cardiac glycosides, penicillin (intravenous administration), tetracycline, derivatives of a fenotiazin.

Incompatibility. Флюксум® - acid polysaccharide which forms insoluble complexes with the bases. For this reason, Flyuksum's solution is incompatible with solutions of vitamin K, vitamins of group B, a hydrocortisone, hyaluronidase, calcium of a gluconate, the quarternary ammonium bases, chloramphenicol, tetracycline and aminoglycosides.

Contraindications:

• Hypersensitivity to a parnaparin or other components of drug, to heparin and products from pork.
• Carrying out regional anesthesia at the patients receiving Flyuksum® with the medical purpose.
• The states or diseases complicated by bleeding and also with the increased risk of bleeding or predisposition to bleedings: disturbances of a hemostasis (except for the consumption coagulopathy which is not caused by heparin), a peptic ulcer of a stomach and 12 - a perstny gut and digestive tract erosive cankers in the period of an aggravation, angiodysplasias, a horioretinopatiya, a hemorrhagic stroke.
• The thrombocytopenia induced parnapariny sodium including in the anamnesis.
• An acute bacterial endocarditis (except for a prosthesis endocarditis).
• Heavy uncontrollable arterial hypertension: the arterial pressure (AP) is 180/100 mm Hg.
• A severe craniocereberal injury in the postoperative period.
• Simultaneous use with salicylates and other non-steroidal anti-inflammatory drugs, antiagregantny medicines (klopidogret, Dipiridamolum, и.т.д), Sulfinpyrazonum and a combination of high doses of a parnaparin of sodium with tiklopidiny.
• Children's age up to 18 years (efficiency and safety are not established).

With care: a renal and liver failure, slight and moderate arterial hypertension, a peptic ulcer of a stomach and a 12-perstny gut and erozivnoyazvenny gastrointestinal tract diseases in the anamnesis or other diseases / states in the anamnesis which can be complicated by bleeding, the geparinindutsirovanny thrombocytopenia and thrombocytopenia caused by other low-molecular heparins including in the anamnesis, a horioretinopatiya in the anamnesis, diseases of a head and spinal cord in the postoperative period, simultaneous use with indirect anticoagulants, system glucocorticosteroids (GKS), a dextran (for parenteral use), a combination of low doses of a parnaparin of sodium with tiklopidiny.

Overdose:

At accidental overdose bleeding which is not observed at use of drug in therapeutic doses can develop.

For neutralization of effect of drug it is necessary to appoint protamin sulfate intravenously at the rate of 0,6 ml of protamin of sulfate to 0,1 ml of Flyuksum.

Storage conditions:

To store at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 3 years. Not to use after the term specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Флюксум® solution for hypodermic introduction 3200 Anti-ha ml ME/0,3, 4250 Anti-ha ml ME/0,4, 6400 Anti-ha ml ME/0,6. On 0,3, 0,4 or 0,6 ml of drug in the syringe from neutral glass like I (Evr. T), completed with a needle in a case; on 2 syringes in the blister. On 3 blisters together with the application instruction in a cardboard pack