Active substanceParnaparin sodiumParnaparin sodium
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  • Fluxum®
    solution PC 
  • Dosage form: & nbsphypodermic solution
    Composition:

    Composition per 1 syringe:

    Active Ingredient:

    parnaparin sodium 3200/4250/6400 anti-ha ME
    Excipients: water for injection up to 0.3 / 0.4 / 0.6 ml

    Description:Transparent liquid from colorless to light yellow color.
    Pharmacotherapeutic group:anticoagulant
    ATX: & nbsp

    B.01.A.B   Heparin and its derivatives

    Pharmacodynamics:

    Fluxum® contains active ingredient parnaparin sodium, a low molecular weight glycosaminoglycan with a molecular weight of 4000 to 6000 Da (average molecular weight of about 5000 Da), which is obtained during the depolymerization of heparin isolated from the porcine small intestine mucosa.

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

    Pharmacokinetics:

    The pharmacokinetics of sodium paraparin is linear in the dose range from 3200 anti-Xa ME up to 12800 anti-Ha ME . After subcutaneous (sc) injection of a single dose, the maximum anti-Ha activity in plasma is created after 2-3 hours. Then there is a decrease in activity, which, however, after 12 hours after the dose is still determined. The half-life is about 6 hours. With repeated dosing, the steady state of pharmacokinetics is observed on day 3 with the drug at a dose of 3200 anti-Xa ME 2 times a day and on day 4 when administered at a dose of 6400 anti-Xa ME once a day.

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

    Prophylaxis of deep vein thrombosis (DVT)

    - at general surgical and orthopedic operations

    - in patients with a high risk of developing deep vein thrombosis.

    Treatment of deep vein thrombosis, postthrombophlebitic syndrome, chronic venous insufficiency, acute thrombophlebitis of superficial veins, varicophlebitis.
    Contraindications:

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

    - Conducting regional anesthesia in patients receiving Fluxum® for medical purposes.

    - Conditions or diseases complicated by bleeding, as well as an increased risk of bleeding or a predisposition to bleeding: violations of hemostasis (with the exception of coagulopathy of consumption not caused by heparin), peptic ulcer and 12 duodenal ulcer and erosive-ulcerative lesions of the gastrointestinal tract during the period exacerbations, angiodysplasia, chorioretinopathy, hemorrhagic stroke.

    - Thrombocytopenia induced by parnaparin sodium, including in the anamnesis.

    - Acute bacterial endocarditis (with the exception of endocarditis of the prosthesis).

    - Severe uncontrolled arterial hypertension: blood pressure (BP)> 180/100 mmHg.

    - Severe craniocerebral injury in the postoperative period.

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

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

    Carefully:renal and hepatic insufficiency, mild to moderate hypertension, peptic ulcer and duodenal ulcer and erosive ulcerative gastrointestinal lesions in history, or other ailments / conditions in history that may be complicated by bleeding, heparin-induced thrombocytopenia and thrombocytopenia due to other low molecular weight heparins , including in history, history of chorioretinopathy, head and spinal cord disease in the postoperative period, concurrently applied with indirect anticoagulants, systemic glucocorticosteroids (GCS), dextrin (for parenteral use), a combination of low doses of sodium paraparin with ticlopidine.
    Pregnancy and lactation:

    The animal studies did not show the teratogenic and embryotoxic effects of sodium paraparin.

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

    However, since the risk of the toxic effect of sodium parapaparin on the fetus can not be ruled out completely, then during pregnancy, the drug should be taken only in case of emergency and under the direct supervision of a doctor. If you need to use the drug during lactation, breastfeeding should be discontinued.

    Dosing and Administration:

    Fluxum® is injected into the subcutaneous tissue of the stomach, into the thickness of the skin fold. The needle is located perpendicular to the fold, between the thumb and forefinger. The skin fold is held until the end of the injection. The injection site must be changed.

    Prophylaxis of DVT in general and orthopedic surgery and in patients with elevated risk of DVT general surgery

    0.3 ml (3200 anti-Ha ME) 2 hours prior to surgery. Then 1 time / day for at least 7 days. Orthopedic surgery and in patients with elevated risk of DVT

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

    Treatment

    DVT

    0.6 ml (6400 anti-Xa ME) 2 times a day for at least 7-10 days.If necessary, treatment can begin with a slow infusion of 1.2 ml (12800 anti-Xa ME) within 3-5 days. After cupping the acute phase of the disease, it is recommended to continue the administration of the drug in

    a dose of 0.6 ml (6400 anti-Ha ME) or 0.4 ml (4250 anti-Xa ME) within 10-20 days. Post-thrombophlebitic syndrome and chronic venous insufficiency By 0.6 ml (6400 anti-Xa ME) or 0.4 ml (4250 anti-Xa ME) or 0.3 ml (3200 anti-Xa ME) depending on the severity of the disease once a day for at least 30 days.

    Acute thrombophlebitis of superficial veins, varicophlebitis

    By 0.6 ml (6400 anti-Xa ME) or 0.4 ml (4250 anti-Xa ME) or 0.3 ml (3200 anti-Xa ME) depending on the severity of the disease once a day for at least 20 days.

    Side effects:Sometimes there are cases of thrombocytopenia, allergic reactions, hematoma and necrosis of the skin at the injection site. Necrosis of the skin may be preceded by purpura or erythematous painful foci with or without common symptoms. An increase in the activity of "liver" transaminases may be observed. In isolated cases, there is spinal or epidural hematoma associated with the prophylactic use of the drug during spinal, epidural and lumbar puncture.Hematoma causes various degrees of severity of neurological disorders, including persistent or irreversible paralysis.
    Overdose:

    In case of an accidental overdose, bleeding may occur, which is not observed when the drug is used in therapeutic doses. To neutralize the effect of the drug, it is necessary to appoint Protamine sulfate intravenously, based on 0.6 ml of protamine sulfate per 0.1 ml of Fluxum.

    Interaction:

    Medicinal combinations that are not recommended:

    Acetylsalicylic acid other salicylates, NSAIDs: Increased risk of bleeding due ashitrombotsitarnogo action and the damaging effect on the mucous membrane of the gastrointestinal tract of these drugs.

    Ticlopidine: increased risk of bleeding due to antiplatelet action.

    It is not recommended joint use with high therapeutic doses of parnaparin sodium. When used together with low prophylactic doses of sodium paraparin, careful clinical observation and monitoring of coagulation factors is necessary.

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

    Sulfur: increased risk of bleeding.

    Medicinal combinations, which Motyr apply from caution:

    Oral anticoagulants, increased anticoagulant action. When replacing parnaparin sodium with oral anticoagulants, careful monitoring of the patient is necessary. To assess the effect of these drugs on hemostasis, blood tests should be taken before the appointment of parnaparin sodium.

    System GCS: increased risk of bleeding when taking GCS in high doses for more than 10 days due to damage to the mucous membrane of the gastrointestinal tract and direct exposure to the vessel wall.

    The use of sodium parnaparin in conjunction with GCS should be justified and testedauditeь this therapy under the supervision of a doctor

    Dextual (for parenteral use): increased risk of bleeding due to anthrombocyte action. When combined, a dose adjustment of sodium paraparin is necessary, so that the reduction in blood clotting values ​​is no more than 1.5 times

    The effect of sodium parnaparin is reduced when combined with ascorbic acid, angiogastamine drugs, cardiac glycosides, penicillin (intravenous administration), tetracycline, phenothiazine derivatives

    Incompatibility

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

    Special instructions:

    Fluxum ® can not be administered intramuscularly.

    Thrombocytopenia induced by heparin

    It is known that Flyuksum® as heparin itself and other low molecular weight heparins can cause thrombocytopenia. Heparin-induced thrombocytopenia usually develop 4-10 days after the start of treatment, or earlier in repeated occasions. In 10-20% of patients with early mild occurs thrombocytopenia (platelet count> 100,000 / ul), which may regress or persist with continued treatment. As a result, formation of antibodies to the complex of heparin / platelet factor 4, in some cases, may develop a more severe form of immune, heparin-induced thrombocytopenia II type, followed by thrombus formation and thromboembolism in the cerebral arteries, lungs, and other lower limb. Often with fatal consequences.During the treatment with Fluxum, patients should be carefully monitored. For long-term treatment, the number of platelets should be determined before the beginning of Fluxum therapy and 2 times a week during the first month, and then monitoring of the platelet count may be more rare. With extreme caution, Fluxum® should be given to patients who have a history of thrombocytopenia caused by heparin or other low-molecular-weight heparin, the platelet count must be calculated 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, low-molecular-weight heparin should be discontinued as early as possible. If thrombocytopenia is less than 100,000 / mm3, with the onset and progression of thrombosis, Fluxum® should be discontinued and the patient transferred to another anticoagulant therapy. Switching to oral anticoagulant therapy in these cases is not recommended, since it is known about the progression of thrombosis.

    If suspicion of heparin-induced thrombocytopenia, platelet aggregation assays in vitro do not have a large diagnostic value, it is necessary to consult specialists.

    Spinal / epidural anesthesia

    Conducting spinal or epidural anesthesia, spinal epidural analgesia or lumbar puncture against the background of preventive use of Fluxum, as well as 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 concomitant NSAIDs, antiplatelet drugs or anticoagulants, in trauma or repeated spinal punctures, the presence of initial hemostasis disorders or in elderly patients. If anesthesia / analgesia of this type is necessary, against the backdrop of the prophylactic use of Fluxum, the presence of these risk factors should be carefully checked before these interventions.

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

    Special attention should be paid to patients who received Fluxum® before or after epidural or spinal anesthesia, checking for neurologic symptoms such as back pain, sensory and motor disorders (numbness or weakness in the lower extremities), impaired bowel or bladder function. Patients should be informed of the need to seek immediate medical attention if these symptoms occur. If suspected epidural or spinal hematoma requires immediate diagnosis and treatment, including decompression of the spinal cord.

    Low molecular weight heparins differ in molecular weight and specific activity, in doses, therefore, it is not recommended to alternate the use of Fluxum with other low molecular weight heparins during the treatment.

    When skin necrosis occurs, treatment with Fluxum should be discontinued.

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

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

    Form release / dosage:

    Fluxum® subcutaneous solution 3200 anti-Xa IU / 0.3 ml, 4250 anti-Ha IU / 0.4 ml, 6400 anti-Ha IU / 0, b ml. For 0.3, 0.4 or 0.6 ml of the drug in a syringe made from neutral glass Type I (Hebrew F), completed with a needle in a case; 2 syringes per blister. By 3 blisters together with instructions for use in a cardboard pack.

    Packaging:solution for subcutaneous administration of 3200 anti-Xa IU / 0.3 ml, 4250 anti-Xa IU / 0.4 ml, 6400 anti-Ha IU / 0.6 ml (syringe) 0.3 / 0.4 / 0.6 ml x 6 (carton pack) (complete with needle in a case)
    Storage conditions:

    Store at a temperature not exceeding 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    Zgoda

    Do not use after the time specified on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002292
    Date of registration:05.11.2013
    The owner of the registration certificate:Alfa Wassermann SpAAlfa Wassermann SpA Italy
    Manufacturer: & nbsp
    Representation: & nbspALPHA VASSERMANN LLC ALPHA VASSERMANN LLC Italy
    Information update date: & nbsp20.08.2015
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