Active substanceSodium HeparinSodium Heparin
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  • Dosage form: & nbspsolution for intravenous and subcutaneous administration of 5000 IU / ml
    Composition:

    In 1 ml contains:

    active substance: heparin sodium 5000 ME

    Excipients: benzyl alcohol - 9 mg; sodium chloride - 3.4 mg; 0.1 M solution of hydrochloric acid or 0.1 M sodium hydroxide solution to pH from 5.5 to 7.5; water for injection up to 1 ml.

    Description:Transparent colorless or colorless with a yellowish tinge of liquid.
    Pharmacotherapeutic group:Anticoagulant of direct action
    ATX: & nbsp

    B.01.A.B.01   Heparin

    Pharmacodynamics:

    Heparin sodium is a biological preparation. Sodium Heparin is an inhomogeneous mixture of polysaccharides with a molecular weight from 2000 to 30,000 Da (predominantly 15000-18000 Da), characterized by the heterogeneity of the chemical structure (linearity variability, different degree of sulfation, different arrangement of pharmacologically active fragments in the polysaccharide chain).

    Pharmacological action - anticoagulant.

    The mechanism of action of heparin is based primarily on its binding to antithrombin III, which is a natural inhibitor of activated blood coagulation factors: IIa (thrombin), IXa, Xa, XIa and XIIa. Heparin binds to antithrombin III and causes conformational changes in its molecule. As a result, binding of antithrombia III to blood coagulation factors IIa (thrombin), IXa, Xa, XIa and XIIa is accelerated, and their enzymatic activity is blocked. The binding of heparin with antithrombin III is of an electrostatic nature and depends to a large extent on the length and composition of the molecule (for the binding of heparin to antithrombin III, a pentasaccharide sequence containing 3-O-sulphated glucosamine). The greatest importance is the ability of heparin in combination with antithrombin III to inhibit coagulation factors IIa (thrombin) and Ha. The ratio of heparin sodium activity with respect to factor Xa to its activity with respect to factor IIa is 0.9-1.1.

    Heparin reduces blood viscosity, reduces vascular permeability, stimulated by bradykinin, histamine and other endogenous factors, and thus prevents the development of stasis.Heparin is able to sorb on the surface of membranes of the endothelium and blood cells, increasing their negative charge, which prevents adhesion and aggregation of platelets. Heparin slows hyperplasia of smooth muscles, activates lipoprotein lipase and, thus, has a hypolipidemic effect and prevents the development of atherosclerosis.

    Heparin binds some components of the complement system, reducing its activity, interferes with the cooperation of lymphocytes and the formation of immunoglobulins, binds histamine, serotonin (ie has anti-allergic effect). Heparin increases renal blood flow, increases the resistance of the brain vessels, reduces the activity of brain hyaluronidase, reduces the activity of the surfactant in the lungs, suppresses excessive synthesis of aldosterone in the adrenal cortex, binds adrenaline, modulates the ovarian response to hormonal stimuli, and increases parathyroid hormone activity. As a result of interaction with enzymes, heparin can increase the activity of brain tyrosine hydroxylase, pepsinogen, DNA polymerase and reduce the activity of myosin ATPase, pyruvate kinase, RNA polymerase, pepsin.The clinical significance of these effects of heparin remains uncertain and insufficiently studied.

    In acute coronary syndrome without stable rise of the ST segment on the ECG (unstable angina, myocardial infarction without ST segment elevation) heparin sodium in combination with acetylsalicylic acid reduces the risk of myocardial infarction and reduces mortality. With myocardial infarction with ST segment elevation on the ECG heparin sodium is effective in primary percutaneous coronary revascularization in combination with inhibitors of glycoprotein IIb / IIIa receptors and in thrombolytic therapy with streptokinase (increased frequency of revascularization).

    In high doses heparin sodium is effective in pulmonary embolism and venous thrombosis. In small doses heparin sodium effective for the prevention of venous thromboembolism, incl. after surgical operations.

    With intravenous administration, blood clotting slows down almost immediately. With subcutaneous administration, the action of heparin occurs in 40-60 minutes. The duration of the anticoagulant effect of sodium heparin after intravenous and subcutaneous administration is 4-5 hours and 8 hours, respectively.Deficiency of antithrombin III in the blood plasma or in the place of thrombosis can reduce the antithrombotic effect of heparin sodium.

    Pharmacokinetics:

    After subcutaneous administration, the time to reach the maximum concentration in blood plasma is 4-5 hours. The connection with plasma proteins is up to 95%, the volume of distribution is very small -0.06 l / kg (does not leave the vascular bed due to strong binding to plasma proteins). It does not penetrate the placenta and into breast milk. Intensively captured by endothelial cells and cells of the mononuclear-macrophage system (cells of the reticulo-endothelial system), it is concentrated in the liver and spleen. It is metabolized in the liver with the participation of N-desulfamidase and platelet heparinase, which is included in the metabolism of heparin at later stages. Participation in the metabolism of platelet factor IV (anti-heparin factor), as well as the binding of heparin to the macrophage system, explains the rapid biological inactivation and short-term action. Desulfated molecules under the influence of kidney endoglycosidase are converted into low-molecular fragments. The half-life is 1-6 hours (on the average - 1.5 hours); increases with obesity,hepatic and / or renal insufficiency; decreases with thromboembolism of the pulmonary artery, infections, malignant tumors.

    It is excreted by the kidneys, mainly in the form of inactive metabolites, and only with the introduction of high doses is it possible to excrete (up to 50%) unchanged. It is not excreted by hemodialysis.

    Indications:

    - Prevention and treatment of venous thrombosis (including thrombosis of superficial and deep veins of the lower extremities, thrombosis of the renal veins) and pulmonary embolism.

    - Prevention and treatment of thromboembolic complications associated with atrial fibrillation.

    - Prevention and treatment of peripheral arterial embolism (including associated with mitral heart defects).

    - Treatment of acute and chronic coagulopathy of consumption (including the first stage of DIC syndrome).

    - Acute coronary syndrome without stable rise of the ST segment on the ECG (unstable angina, myocardial infarction without ST segment elevation on the ECG).

    - Myocardial infarction with ST segment elevation: with thrombolytic therapy, with primary percutaneous coronary revascularization (balloon angioplasty with or without stenting) and with a high risk of arterial or venous thrombosis and thromboembolism.

    - Prophylaxis and therapy of microthrombogenesis and microcirculation disorders, incl. with hemolytic-uremic syndrome; glomerulonephritis (including lupus nephritis) and with forced diuresis.

    - Prevention of blood coagulation during blood transfusion, extracorporeal circulation systems (extracorporeal circulation in heart surgery, hemosorption, cytarapheresis) and hemodialysis.

    - Treatment of peripheral venous catheters.

    Contraindications:

    - Hypersensitivity to sodium heparin or products of animal origin.

    - Heparin - induced thrombocytopenia (with or without thrombosis) in the anamnesis or at the present time.

    - Bleeding (except when the benefits of sodium heparin outweigh the potential risk).

    - Sodium Heparin Therapeutic dose should not be administered if there is no way to provide regular laboratory monitoring of blood coagulability.

    - Pregnancy and the period of breastfeeding.

    - Newborns, especially premature babies or those with low body weight.

    Carefully:

    Sodium Heparin should be used with caution in pathological conditions associated with an increased risk of bleeding, such as:

    - Diseases of the cardiovascular system: acute and subacute infective endocarditis, severe uncontrolled arterial hypertension, exfoliation of the aorta, aneurysm of cerebral vessels.

    - Diseases of the digestive system: erosive and ulcerative lesions of the digestive system (including stress-induced), varicose veins of the esophagus with cirrhosis of the liver and other diseases, prolonged use of gastric and intestinal drainage, ulcerative colitis, hemorrhoids.

    - Diseases of blood and blood lymphatic system: leukemia, hemophilia, thrombocytopenia, hemorrhagic diathesis.

    - Diseases of the central nervous system: hemorrhagic stroke, craniocerebral trauma.

    - Malignant neoplasms.

    - Congenital deficiency of antithrombin III and substitution therapy with antithrombin III preparations (lower doses of heparin should be used to reduce the risk of bleeding).

    - Other physiological and pathological conditions: the period of menstruation, the threat of miscarriage, the early postpartum period, severe liver disease with a violation of protein-synthetic function, chronic renal failure,recent surgery for the eyes, brain or spinal cord, recent spinal (lumbar) puncture or epidural anesthesia, proliferative diabetic retinopathy, vasculitis, advanced age (especially in women).

    The use of heparin sodium is possible in cases where the expected benefit of therapy outweighs the potential risk.

    Pregnancy and lactation:

    Controlled clinical studies of the use of heparin sodium in pregnant women have not been conducted. According to published data, the use of heparin during pregnancy does not adversely affect the fetus. In studies in humans and animals, it was found that heparin sodium does not penetrate the placenta. Sodium Heparin not excreted in breast milk.

    The use of heparin sodium during pregnancy or during breastfeeding is possible only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus or child. Do not use heparin sodium preparations containing benzyl alcohol.

    Dosing and Administration:

    Sodium heparin is administered intravenously (as a continuous infusion or repeated bolus injections) or subcutaneously. Sodium Heparin can not be administered intramuscularly because of the risk of developing intramuscular hematomas.

    Subcutaneous injections are preferably performed in the region of the anterior abdominal wall. As an exception, you can use other places of administration (the external surface of the thigh, shoulder) with a sufficiently developed subcutaneous adipose tissue. It is not recommended to re-enter heparin sodium in places of previous injections.

    Recommended therapeutic (complete) doses of heparin sodium for adults patients:

    Continuous

    intravenous

    infusion

    Initial dose

    5000-10000 ME in / in streaming

    Continuous infusion

    20000-40000 IU / day

    (the rate of administration is about 1000 IU / h)

    Bolyusnoye

    intravenous

    introduction

    Initial dose:

    10000 ME

    Maintenance doses

    5000-10000 ME every 4-6 hours

    Subcutaneous

    introduction

    Initial dose:

    333 IU / kg (with body weight less than 75 kg - 20,000 ME, with a body weight of 75-90 kg 25000 units, with a body weight of 90-105 kg - 30,000 ME, with a body weight of more than 105 kg - 35,000 ME)

    Maintenance doses

    250 IU / kg (15,000-25,000 ME) every 12 hours.

    Laboratory monitoring of efficacy and safety of heparin sodium therapy

    The dose of sodium heparin must be adjusted on the basis of laboratory indicators of blood coagulability. When sodium heparin is used, it is necessary to monitor activated partial thromboplastin time (APTT) or coagulation time (VSC). The administered dose of sodium heparin is considered adequate if the APTT is 1.5-2.0 times higher than normal values ​​or if the patient's VSK is 2.5-3.0 times higher than the control values.

    With continuous intravenous infusion heparin sodium, it is recommended to determine the initial APTT, then determine the APTT every 4 hours followed by an increase or decrease in the rate of infusion of heparin sodium to achieve the target APTT level (1.5-2 times higher than the norm), then determine the APTT every 6 hours.

    With bolus intravenous administration heparin sodium is recommended to determine the initial APTT, then determine the APTT before each bolus injection followed by an increase or decrease in the administered dose of sodium heparin.

    When administered subcutaneously heparin sodium is recommended to control APTT 4-6 hours after injection, followed by an increase or decrease in the administered dose of heparin sodium.

    When sodium heparin is used in low doses for the prevention of thromboembolic complications, it is not necessary to control the APTT.

    Use of heparin sodium in special clinical situations

    Primary percutaneous coronary angioplasty in acute, coronary syndrome without ST segment elevation and with ST-segment elevation myocardial infarction: Sodium Heparin is administered intravenously bolus at a dose of 70-100 U / kg (unless the use of inhibitors of glycoprotein IIb / IIIa receptors is planned) or in a dose of 50-60 U / kg (when combined with inhibitors of glycoprotein IIb / IIIa receptors).

    Thrombolytic therapy for myocardial infarction with ST segment elevation: Sodium Heparin is administered intravenously bolus at a dose of 60 U / kg (maximum dose 4000 ED), followed by intravenous infusion at a dose of 12 U / kg (not more than 1000 U / h) for 24-48 hours. The target level of APTT is 50-70 seconds or 1.5-2.0 times higher than normal; Control of APTT at 3.6, 12 and 24 hours after initiation of therapy.

    Prevention of thromboembolic complications after surgical interventions using low doses of heparin sodium: s / k, deep in the crease of the skin of the abdomen. The initial dose of 5000 ME 2 hours before the operation.In the postoperative period: 5000 IU every 8-12 hours for 7 days or until the patient's mobility is completely restored (whichever comes first). When sodium heparin is used in low doses for the prevention of thromboembolic complications, it is not necessary to control the APTT.

    Application in cardiovascular surgery in operations with the use of, systems, extracorporeal circulation: the initial dose of sodium heparin is not less than 150 IU / kg body weight. Further heparin sodium is introduced by continuous intravenous infusion at a rate of 15-25 drops / min at 30,000 IU per 1 liter of the infusion solution. The total dose of heparin sodium is usually 300 IU / kg body weight (if the expected duration of the operation is less than 60 minutes) or 400 IU / kg body weight (if the estimated duration of the operation is 60 minutes or more).

    Application for hemodialysis: The initial dose of heparin sodium: 25-30 units / kg (or 10,000 units) intravenously bolus, then a continuous infusion of sodium heparin 20000 IU / 100 mg sodium chloride solution at a rate of 1500-2000 U / hour (unless otherwise specified in the manual for the use of systems for hemodialysis).

    The use of heparin sodium in pediatrics: Adequate controlled trials of the use of heparin sodium in children have not been conducted.These recommendations are based on clinical experience.

    Initial dose: 75-100 U / kg intravenously bolus for 10 minutes

    The maintenance dose: children aged 1-3 months - 25-30 U / kg / hour (800 U / kg / day), children aged 4-12 months - 25-30 U / kg / h (700 U / kg / day), children older than 1 year - 18-20 units / kg / hour (500 units / kg / day) intravenously drip.

    The dose of heparin sodium should be selected taking into account the parameters of blood coagulation (the target level of APTT is 60-85 seconds).

    Side effects:

    Classification of the World Health Organization (WHO) of unwanted drug reactions by frequency of development: very often (> 1/10 appointments); often (> 1/100 and <1/10 of appointments); infrequently (> 1/1000 and <1/100 of prescriptions); rarely (> 1/10000 and <1/1000 appointments); very rarely (<1/10000), including individual messages.

    Hemorrhagic complications: Develop very often. The most typical bleeding from the digestive tract, urinary tract, from the sites of sodium heparin, from postoperative wounds, as well as hemorrhages in areas undergoing pressure. Also, hemorrhages may develop in other internal organs, incl. in the adrenal glands (with the development of acute adrenal insufficiency), retroperitoneal space, ovaries.More frequent bleeding occurs in patients older than 60 years (especially in women).

    Allergic reactions: infrequent - skin hyperemia, rash, itching and burning sensation in the soles, pain in the extremities, hyperthermia, urticaria, rhinitis, conjunctivitis, dyspnea, bronchospasm, angioedema; very rarely - anaphylactic shock.

    Reactions at the site of administration: often - irritation, soreness, hyperemia of the tissues, minor hematoma and ulceration at the injection site, infrequently - histamine-like reactions (including necrosis of the skin at the injection site), very rarely - calcification of soft tissues at the site of administration (mainly in patients with severe chronic renal insufficiency).

    Heparin-induced thrombocytopenia (HIT): a severe immune reaction caused by the formation of antibodies and leading to irreversible aggregation of platelets. It can develop as a background of heparin therapy (rarely), and for several weeks after its termination (very rarely). Clinical manifestations: venous and arterial thromboses (including deep vein thrombosis of legs, pulmonary embolism, thrombosis of cerebral veins, stroke, myocardial infarction,thrombosis of mesenteric and renal arteries, thrombosis of the arteries of the extremities with the development of gangrene).

    Laboratory diagnostics: It should be determined the number of platelets before the appointment of heparin sodium, on the first day of treatment, and then every 2-3 days during the entire treatment period (especially from 6 to 14 days of therapy). With a decrease in the number of platelets below 100 * 109/ l and / or with the development of recurrent thrombosis should immediately be canceled heparin sodium. If necessary, an alternative antithrombotic therapy should be prescribed.

    Therapy and prevention: When a GIT occurs heparin sodium should be immediately canceled. The patient should be warned that in the future he can not be appointed unfractionated heparin (including hemodialysis) and low molecular weight heparins. If the patient needs antithrombotic therapy, then other drugs should be used.

    Other undesirable phenomena:

    From the central nervous system and sensory organs: infrequently, headache, headache.

    From the cardiovascular system: infrequently - lowering blood pressure.

    From the digestive system: infrequent - loss of appetite, nausea, vomiting, diarrhea, often - an increase in the content of "liver" transaminases (ACT and ALT) in blood plasma.

    From the hematopoiesis: often - moderate thrombocytopenia (platelet content 150-100 * 109/ l) not associated with the production of antibodies and not accompanied by thrombosis (may occur in 6-30% of patients receiving heparin); rarely - reversible eosinophilia.

    From the musculoskeletal system: rarely - osteoporosis (with prolonged use of sodium heparin), spontaneous fractures of bones.

    From the endocrine system: rarely - hypoaldosteronism (due to inhibition of aldosterone synthesis).

    From the side of water-electrolyte exchange: rarely - reversible potassium retention, metabolic acidosis.

    Other: infrequently - transient alopecia, very rarely - priapism.

    Laboratory indicators: often - a reversible increase in the content of "liver" transaminases (ACT and ALT); infrequently, an increase in free fatty acids after heparin withdrawal, an increase in thyroxin levels in the blood plasma, a false decrease in cholesterol, a false increase in glucose and incorrect results of bromsulfalein test.

    If any of the side effects indicated in the instructions for use are aggravated, or if there are other undesirable effects not listed in the instructions, you should immediately notify the attending physician.

    Overdose:

    Symptoms: bleeding of varying severity.

    Treatment: with small bleeding caused by an overdose of heparin sodium, it is enough to stop using the drug.

    With large bleeding, excess sodium heparin is neutralized with protamine sulfate. 1 mg of protamine sulfate neutralizes 100 IU of sodium heparin. 1% protamine sulphate solution is administered intravenously very slowly. For every 10 minutes, do not administer more than 50 mg (5 ml) of protamine sulfate. Given the rapid metabolism of heparin, the required dose of protamine decreases with time. To calculate the required dose of sodium protamine, it can be assumed that the half-life of heparin is 30 minutes. When sodium protamine was used, serious anaphylactic reactions with a fatal outcome were noted, and therefore the drug should be administered only under conditions of separation, equipped to provide emergency medical care for anaphylactic shock. Heparin is not excreted by hemodialysis.

    Interaction:

    Pharmaceutical interaction: A solution of sodium heparin is diluted only with physiological solution. A solution of sodium heparin is incompatible with the following substances: alteplase, amikacin sulfate, amiodarone, ampicillin sodium, benzylpenicillin sodium, ciprofloxacin, cytarabine, dacarbazine, danorubicin, diazepam, dobutamine, doxorubicin hydrochloride, droperidol, erythromycin, gentamicin sulfate, haloperidol lactate, hyaluronidase, hydrocortisone sodium succinate, glucose, fat emulsions, idarubicin, kanamycin sulfate, methicillin sodium, netilmicine sulfate, opioids, oxytetracycline hydrochloride, polymyxin B sulfate, promazine hydrochloride, promethazine hydrochloride, streptomycin sulfate, sulfafurazole diethanolamine, tetracycline hydrochloride, tobramycin sulfate, cephalothin sodium, cefaloridine, vancomycin hydrochloride, vinblastine sulfate, labetalol hydrochloride , nicardipine hydrochloride.

    Pharmacokinetic interaction: Sodium Heparin displaces phenytoin, quinidine, propranolol and benzodiazepine derivatives from the sites of their binding to blood plasma proteins, which may lead to an increase in the pharmacological action of the prescribed drugs. Sodium Heparin is bound and inactivated by sodium protamine, polypeptides having an alkaline reaction, and tricyclic antidepressants.

    Pharmacodynamic interaction: The anticoagulant effect of sodium heparin increases with simultaneous use with other drugs that affect hemostasis, including. with antiplatelet drugs (acetylsalicylic acid, clopidogrel, prasugrel, ticlopidine, dipyridamole), anticoagulants of indirect action (warfarin, phenylin, syncumar), thrombolytic drugs (alteplase, streptokinase, urokinase) with non-steroidal anti-inflammatory drugs (phenylbutazone, ibuprofen, indomethacin, diclofenac and others), glucocorticoids and dextrin, which increases the risk of bleeding. In addition, the anticoagulant effect of sodium heparin can be enhanced when combined with hydroxychloroquine, sulfinpyrazone, probenecid, ethacrynic acid, cytostatics, cefamandole, cefotetan, valproic acid, propylthiouracil.

    The anticoagulant effect of sodium heparin decreases with simultaneous use with ACTH,antihistamine drugs, ascorbic acid, ergot alkaloids, nicotine, nitroglycerin, cardiac glycosides, thyroxine, tetracycline and quinine.

    Heparin sodium can reduce the pharmacological action of ACTH, glucocorticoids and insulin.

    Special instructions:

    Transition to warfarin therapy: To ensure a stable anticoagulant action, heparin sodium should be continued in full dosage until a stable target level of INR is reached. After this, the administration of sodium heparin must be stopped.

    Transition to dabigatran therapy: Continuous intravenous administration of sodium heparin should be discontinued immediately after the first dose of dabigatran. With fractional intravenous administration, the patient must take the first dose of dabigatran within 1-2 hours before the scheduled administration of a regular dose of heparin sodium.

    Before routine surgical interventions to reduce blood loss during surgery and during the postoperative period, it is usually recommended to cancel oral anticoagulants (warfarin) and antiplatelet drugs (acetylsalicylic acid, clopidogrel, ticlopidine) 7 days before surgery.As an antithrombotic therapy, it is possible to administer heparin sodium in therapeutic doses. The administration of sodium heparin stops 6 hours before surgery and resumes 6 hours after the end.

    It should avoid intramuscular injection of heparin sodium (because of the possible occurrence of hematoma).

    The use of drugs containing benzyl alcohol as a preservative in newborns (especially in prematurity and in children with reduced body weight) can lead to serious undesirable phenomena (central nervous system depression, metabolic acidosis, gas-breathing) and death. Therefore, newborns and children under 1 year should use heparin sodium preparations that do not contain preservatives.

    Resistance to sodium heparin is often observed with fever, thrombosis, thrombophlebitis, infectious disease, myocardial infarction, malignant neoplasms, and also after surgical interventions and with the deficiency of antithrombin III. In such situations, more thorough laboratory monitoring (control of APTT) is required, including the determination of antithrombin III.

    In people over 60 years (especially women), the risk of bleeding is increased, and therefore the dose of heparin sodium in this category of patients should be reduced.

    During therapy with sodium heparin, you must constantly monitor the clinical symptoms indicating possible bleeding (bleeding of the mucous membranes, hematuria, etc.).

    When using heparin sodium in patients with hypertension should regularly monitor blood pressure and conduct adequate antihypertensive therapy.

    Effect on the ability to drive transp. cf. and fur:Sodium Heparin in most cases does not have a significant effect on the concentration of attention and the speed of psychomotor reactions. In case of adverse reactions from the central nervous system (dizziness, headache), patients are advised to refrain from controlling vehicles and other mechanisms, as well as to use caution when engaging in activities requiring increased concentration of attention and speed of psychomotor reactions.
    Form release / dosage:A solution for intravenous and subcutaneous administration of 5000 IU / ml.
    Packaging:

    5 ml in bottles of neutral colorless glass, corked with a rubber stopper and crimped with an aluminum cap with a protective plastic cover. Each label is labeled or labeled with a quick-fixing paint.

    5 bottles are placed in a pallet made of PVC. 1 or 2 pallets together with instructions for use are placed in a pack of cardboard.

    Storage conditions:Store in a dark place at a temperature of no higher than 25 ° C. Do not freeze! Keep out of the reach of children.
    Shelf life:3 years. Do not use after expiry date.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-002434
    Date of registration:17.04.2014
    Expiration Date:17.04.2019
    The owner of the registration certificate:ALVILS, LTD. ALVILS, LTD. Russia
    Manufacturer: & nbsp
    Representation: & nbspAlvils, OOOAlvils, OOO
    Information update date: & nbsp24.03.2017
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