Fluxum solution 4250ME, 0.4ml No. 6

Prevention of deep vein thrombosis (DVT)

In general surgical and orthopedic operations

In patients with a high risk of deep vein thrombosis.

Treatment of deep vein thrombosis, post-thrombophlebitic syndrome, chronic venous insufficiency, acute superficial vein thrombophlebitis, varicophlebitis

FluxumЃ is injected into the subcutaneous tissue of the abdomen, into the thickness of the skin fold. The needle is positioned perpendicular to the crease, between the thumb and forefinger. The skin fold is held until the end of the injection. The injection site must be changed.

Prevention of DVT in general and orthopedic surgery and in patients at increased risk of DVT

general surgery

0.3 ml (3200 anti-Xa IU) 2 hours before surgery. Then 1 time / day for at least 7 days.

Orthopedic surgery and in patients at increased risk of DVT

0.4 ml (4250 anti-Xa IU) 12 hours before and after surgery, then 1 time / day during the postoperative period, not less than 10 days.

Treatment

DVT

0.6 ml (6400 anti-Ha IU) 2 times a day for at least 7-10 days. If necessary, treatment can be started with a slow infusion of 1.2 ml (12800 anti-Xa IU) over 3-5 days. After stopping the acute phase of the disease, it is recommended to continue subcutaneous administration of the drug in a dose of 0.6 ml (6400 anti-Ha ME) or 0.4 ml (4250 anti-Ha ME) for 10-20 days.

Postthrombophlebitis syndrome and chronic venous insufficiency

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 the severity of the disease, once a day for at least 30 days.

Acute thrombophlebitis of superficial veins, varicophlebitis

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 the severity of the disease, once a day for at least 20 days.

Composition for 1 syringe:

Active Ingredient:

parnaparin sodium 3200/4250/6400 anti-Ha IU

Excipients : water for injection up to 0.3 / 0.4 / 0.6 ml

Hypersensitivity to parnaparin or other components of the drug, to heparin and pork products.

Ј Conducting regional anesthesia in patients receiving FluxumЃ for therapeutic purposes.

Conditions or diseases complicated by bleeding, as well as with an increased risk of bleeding or a predisposition to bleeding: disorders of hemostasis (except for coagulopathy of consumption not caused by heparin), gastric ulcer and 12 duodenal ulcer and erosive and ulcerative lesions of the gastrointestinal tract in period of exacerbation, angiodysplasia, chorioretinopathy, hemorrhagic stroke.

Ј Thrombocytopenia induced by sodium parnaparin, including a history.

Ј Acute bacterial endocarditis (except for endocarditis of the prosthesis).

Severe uncontrolled arterial hypertension: blood pressure (BP)

? 180/100 mm Hg

Ј Severe traumatic brain injury in the postoperative period.

Ј Simultaneous use with salicylates and other non-steroidal anti-inflammatory drugs, antiplatelet drugs (clopidogrel, dipyridamole, etc.), sulfinpyrazone and a combination of high doses of sodium parnaparin with ticlopidine.

Children under 18 years of age (efficacy and safety have not been established)

With caution : renal and hepatic failure, mild and moderate arterial hypertension, peptic ulcer and 12 duodenal ulcer and erosive and ulcerative lesions of the gastrointestinal tract in history or other diseases / conditions in history that may be complicated by bleeding, heparin-induced thrombocytopenia and thrombocytopenia caused by other low-molecular-weight heparins, including a history of chorioretinopathy in history, diseases of the brain and spinal cord in the postoperative period, simultaneous use with indirect anticoagulants, systemic glucocorticosteroids (GCS), dextran (for parenteral dose administration), combination of low sodium ticlopidine.

Pharmacotherapeutic group: direct-acting anticoagulant

Pharmacodynamics

FluxumЃ contains the active ingredient parnaparin sodium, a low molecular weight glycosaminoglycan with a molecular weight of 4000 to 6000 Da (average molecular weight about 5000 Da), which is obtained in the process of depolymerization of heparin isolated from the mucous membrane of the small intestine of a pig.

Parnaparin sodium has an antithrombotic effect. In vitro and in vivo, it suppresses factor Xa to a large extent, has little effect on factor II a and on partial activated thromboplastin time (APTT). The antithrombotic activity (anti-Xa) of the drug is superior to the anticoagulant (anti-IIa). Thus, the ratio of anti-Xa / anti-IIa activity is from 1.5 to 3 (in comparison with heparin, for which this ratio is equal to 1). Parnaparin sodium does not have a proaggregant platelet effect.

Pharmacokinetics

The pharmacokinetics of parnaparin sodium is linear in the dose range from 3200 anti-Xa IU to 12800 anti-Xa IU. After subcutaneous (s / c) administration of a single dose, the maximum anti-Xa activity in plasma is created in 2 to 3 hours. A decrease in activity is then observed, which, however, is still detectable 12 hours after dosing. The half-life is about 6 hours. With repeated dosing, a steady state of pharmacokinetics is observed on day 3 with the use of the drug at a dose of 3200 anti-Xa IU 2 times a day and on day 4 with a dose of 6400 anti-Xa IU once a day.

The bioavailability of parnaparin sodium, which is assessed by its anti-Xa activity, is close to 100%. The area under the concentration-time curve (AUC) is linear with dose. With the subcutaneous route of administration, the pharmacokinetic profile of a-Xa activity is more favorable compared to the profile with intravenous administration, since it is characterized by a smoother curve with fewer peaks and a slower decrease in activity. Parnaparin sodium is distributed to the liver and kidneys. In the liver, it is metabolized to inactive compounds and excreted from the body through the kidneys.

Indications for use

Prevention of deep vein thrombosis (DVT)

In general surgical and orthopedic operations

In patients with a high risk of deep vein thrombosis .

Treatment of deep vein thrombosis, post-thrombophlebitic syndrome, chronic venous insufficiency, acute superficial vein thrombophlebitis, varicophlebitis

Contraindications

Ј Hypersensitivity to parnaparin or other components of the drug, to heparin and pork products.

Ј Conducting regional anesthesia in patients receiving FluxumЃ for therapeutic purposes.

Conditions or diseases complicated by bleeding, as well as with an increased risk of bleeding or a predisposition to bleeding: disorders of hemostasis (except for coagulopathy of consumption not caused by heparin), gastric ulcer and 12 duodenal ulcer and erosive and ulcerative lesions of the gastrointestinal tract in period of exacerbation, angiodysplasia, chorioretinopathy, hemorrhagic stroke.

Ј Thrombocytopenia induced by sodium parnaparin, including a history.

Ј Acute bacterial endocarditis (except for endocarditis of the prosthesis).

Severe uncontrolled arterial hypertension: blood pressure (BP)

? 180/100 mm Hg

Ј Severe traumatic brain injury in the postoperative period.

Ј Simultaneous use with salicylates and other non-steroidal anti-inflammatory drugs, antiplatelet drugs (clopidogrel, dipyridamole, etc.), sulfinpyrazone and a combination of high doses of sodium parnaparin with ticlopidine.

Children under 18 years of age (efficacy and safety have not been established)

With caution : renal and hepatic failure, mild and moderate arterial hypertension, peptic ulcer and 12 duodenal ulcer and erosive and ulcerative lesions of the gastrointestinal tract in history or other diseases / conditions in history that may be complicated by bleeding, heparin-induced thrombocytopenia and thrombocytopenia caused by other low-molecular-weight heparins, including a history of chorioretinopathy in history, diseases of the brain and spinal cord in the postoperative period, simultaneous use with indirect anticoagulants, systemic glucocorticosteroids (GCS), dextran (for parenteral dose administration), combination of low sodium ticlopidine.

Application during pregnancy and lactation

Animal studies have not shown the teratogenic and embryotoxic effects of sodium parnaparin.

There are no convincing data on penetration through the placental barrier and on excretion into breast milk.

However, since the risk of the toxic effect of sodium parnaparin on the fetus cannot be completely excluded, during pregnancy the drug should be taken only if absolutely necessary and under the direct supervision of a physician. If necessary, the use of the drug during lactation, breastfeeding should be discontinued.

Method of administration and dosage

FluxumЃ is injected into the subcutaneous tissue of the abdomen, into the thickness of the skin fold. The needle is positioned perpendicular to the crease, between the thumb and forefinger. The skin fold is held until the end of the injection. The injection site must be changed.

Prevention of DVT in general and orthopedic surgery and in patients at increased risk of DVT

general surgery

0.3 ml (3200 anti-Xa IU) 2 hours before surgery. Then 1 time / day for at least 7 days.

Orthopedic surgery and in patients at increased risk of DVT

0.4 ml (4250 anti-Xa IU) 12 hours before and after surgery, then 1 time / day during the postoperative period, not less than 10 days.

Treatment

DVT

0.6 ml (6400 anti-Ha IU) 2 times a day for at least 7-10 days. If necessary, treatment can be started with a slow infusion of 1.2 ml (12800 anti-Xa IU) over 3-5 days. After stopping the acute phase of the disease, it is recommended to continue subcutaneous administration of the drug in a dose of 0.6 ml (6400 anti-Ha ME) or 0.4 ml (4250 anti-Ha ME) for 10-20 days.

Postthrombophlebitis syndrome and chronic venous insufficiency

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 the severity of the disease, once a day for at least 30 days.

Acute thrombophlebitis of superficial veins, varicophlebitis

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 the severity of the disease, once a day for at least 20 days.

Side effect

Sometimes there are cases of thrombocytopenia, allergic reactions, hematoma and skin necrosis at the injection site. Skin necrosis may be preceded by purpura or erythematous lesions with or without general symptoms. There may be an increase in activity

'Hepatic' transaminases. In isolated cases, there is a spinal or epidural hematoma associated with the prophylactic use of the drug during spinal, epidural and lumbar puncture. Hematoma causes neurological damage of varying severity, including permanent or irreversible paralysis.

Overdose

In case of an accidental overdose, bleeding may develop, which is not observed when using the drug in therapeutic doses. To neutralize the effect of the drug, it is necessary to prescribe protamine sulfate intravenously at the rate of 0.6 ml of protamine sulfate per 0.1 ml of Fluxum.

Interaction with other medicinal products

Drug combinations that are not recommended:

Acetylsalicylic acid, other salicylates, NSAIDs : the risk of bleeding is increased due to the antiplatelet effect and the damaging effect on the mucous membrane of the gastrointestinal tract of these drugs.

Ticlopidine : increased risk of bleeding due to antiplatelet action. Joint use with high therapeutic doses of parnaparin sodium is not recommended. When used together with low prophylactic doses of parnaparin sodium, careful clinical observation and monitoring of clotting parameters is necessary.

Other antiplatelet drugs (eg, clopidogrel, dipyridamole): increased risk of bleeding.

Sulfinpyrazone : increased risk of bleeding.

Medicinal combinations that can be used with caution: Oral anticoagulants : increased anticoagulant action. Careful monitoring of the patient is necessary when replacing parnaparin sodium with oral anticoagulants. To

to assess the effect of these drugs on hemostasis, blood tests should be taken before prescribing

parnaparine sodium.

Systemic corticosteroids: increased risk of bleeding when taking corticosteroids in high doses for more than 10 days due to damage to the mucous membrane of the gastrointestinal tract and direct exposure to the walls of blood vessels. The use of parnaparin sodium in conjunction with corticosteroids must be justified and this therapy should be carried out under the supervision of a physician.

Dextran (for parenteral use) : increased risk of bleeding due to antiplatelet action. When used together, it is necessary to adjust the dose of sodium parnaparin so that the decrease in blood coagulation parameters is no more than 1.5 times.

The effect of parnaparin sodium decreases when combined with ascorbic acid, antihistamines, cardiac glycosides, penicillin (intravenous administration), tetracycline, phenothiazine derivatives.

Incompatibility

FluxumЃ is an acidic polysaccharide that forms insoluble complexes with bases. For this reason, Fluxum solution is incompatible with solutions of vitamin K, B vitamins, hydrocortisone, hyaluronidase, calcium gluconate, quaternary ammonium bases, chloramphenicol, tetracycline and aminoglycosides.

special instructions

FluxumЃ cannot be administered intramuscularly. Heparin-induced thrombocytopenia

It is known that FluxumЃ, like heparin itself and other low molecular weight heparins, can cause thrombocytopenia. Heparin-induced thrombocytopenia usually develops within 4-10 days from the start of treatment or earlier in case of repeated cases. In 10-20% of patients, early mild thrombocytopenia (platelets> 100,000 / ?L) occurs, which may persist or regress with continued treatment. As a result of the formation of antibodies to the heparin / platelet factor 4 complex, in some cases, a more severe immune form, heparin-induced thrombocytopenia of type II, may develop, followed by thrombosis and thromboembolism in the arteries of the brain, lungs, lower extremities, etc., often with a fatal outcome. During the period of treatment with Fluxum, patients must be carefully observed.With long-term treatment, the platelet count should be determined before starting therapy with Fluxum and 2 times a week during the first month, and then monitoring the platelet count may be more rare. With extreme caution, FluxumЃ should be prescribed to patients with a history of thrombocytopenia caused by heparin or other low molecular weight heparin, counting

they need to produce platelet counts every day. If thrombocytopenia occurs during treatment with heparin, an alternative treatment may be

therapy with low molecular weight heparins. In this case, the number of platelets should be determined daily and, if thrombocytopenia persists, then low molecular weight heparin should be canceled as soon as possible. If thrombocytopenia is less than 100,000 / ?l, if thrombosis occurs and progresses, FluxumЃ should be canceled and the patient should be transferred to another anticoagulant therapy. Switching to therapy with oral anticoagulants in these cases is not recommended, as the progression of thrombosis is known.

If heparin-induced thrombocytopenia is suspected, in vitro platelet aggregation tests are not of great diagnostic value, and specialist advice is required.

Spinal / epidural anesthesia

Spinal or epidural anesthesia, spinal epidural analgesia or lumbar puncture against the background of prophylactic use of Fluxum, like other low molecular weight heparins, can be complicated by spinal or epidural hematoma with the development of persistent or irreversible paralysis. The risk of these complications increases with the use of epidural catheters, with the use of concomitant NSAIDs, antiplatelet drugs or anticoagulants, with trauma or repeated spinal punctures, the presence of underlying hemostasis disorders, or in elderly patients. If it is necessary to carry out anesthesia / analgesia of this type against the background of prophylactic use of Fluxum, the presence of these risk factors should be carefully checked before these interventions.

Usually, spinal catheters are inserted no earlier than 8-12 hours after the last prophylactic dose of low molecular weight heparin. Do not administer FluxumЃ 2-4 hours before and after insertion / removal of the catheter. Injection should be delayed or canceled if blood is aspirated from the spinal canal during spinal or epidural anesthesia. The catheter should be removed as late as possible after (8-12 hours) the last prophylactic injection of Fluxum.

—ледует удел¤ть особое внимание пациентам, которые получали ‘люксумЃ до или после эпидуральной или спинальной анестезии, прове𤤠наличие неврологических симптомов, таких как боль в по¤снице, чувствительные и двигательные расстройства (онемение или слабость в нижних конечност¤х), нарушение функции кишечника или мочевого пузыр¤. ѕациентов следует информировать о необходимости немедленного обращени¤ к врачу при по¤влении указанных симптомов. ѕри подозрении на эпидуральную или спинальную

гематому требуетс¤ немедленна¤ диагностика и лечение, включа¤ декомпрессию спинного мозга.

Ќизкомолекул¤рные гепарины отличаютс¤ друг от друга по молекул¤рной массе и

специфической активности, дозам, поэтому не рекомендуетс¤ чередовать применение ‘люксума с другими низкомолекул¤рными гепаринами в процессе лечени¤.

If skin necrosis occurs, treatment with Fluxum must be interrupted.

Impact on the ability to drive vehicles

FluxumЃ does not affect the ability to drive vehicles and engage in activities that require increased attention and speed of psychomotor reactions.