Heparin injection solution 5000e for ml ampoules 5ml N5
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Active ingredients
Sodium heparin
Release form
Solution
Composition
Heparin sodium 5000 IU. Auxiliary substances: benzyl alcohol 9 mg, sodium chloride 3.4 mg, water d / and up to 1 ml.
Pharmacological effect
The mechanism of action of heparin sodium 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. Sodium heparin is bound by antithrombin III and causes conformational changes in its molecule. As a result, the binding of antithrombin III to coagulation factors IIa (thrombin), IXa, Xa, XIa and XIIa is accelerated and their enzymatic activity is blocked. The binding of sodium heparin to antithrombin III is of an electrostatic nature and is largely dependent on the length and composition of the molecule (to bind sodium heparin to antithrombin III, a penta-saccharide sequence containing 3-O-sulfated glucosamine is required). The ability of sodium heparin in combination with antithrombin III to inhibit coagulation factors IIa (thrombin) and Xa is of the greatest importance. The ratio of the activity of heparin sodium in relation to factor Xa to its activity in relation to factor IIa is 0.9-1.1. Sodium heparin reduces blood viscosity, reduces vascular permeability, stimulated by bradykinin, histamine and other endogenous factors, and thus prevents the development of stasis. Sodium heparin can be sorbed on the surface of the endothelium membranes and blood cells, increasing their negative charge, which prevents the adhesion and aggregation of platelets. Sodium heparin slows smooth muscle hyperplasia, activates lipoprotein lipase and, thus, has a lipid-lowering effect and prevents the development of atherosclerosis. Heparin sodium binds some components of the complement system, reducing its activity, prevents the cooperation of lymphocytes and the formation of immunoglobulins, binds histamine, serotonin (that is, it has antiallergic effect). Sodium heparin increases renal blood flow, increases vascular resistance in the brain, reduces brain hyaluronidase activity, reduces surfactant activity in the lungs, suppresses excessive aldosterone synthesis in the adrenal cortex, binds adrenaline, modulates the ovarian response to hormonal stimuli, enhances the activity of parathyroid hormone.As a result of interaction with enzymes, sodium heparin can increase the activity of brain tyrosine hydroxylase, pepsinogen, DNA polymerase and reduce the activity of myosin ATPase, pyruvate kinase, PNK polymerase, pepsin. The clinical significance of these effects of sodium heparin remains uncertain and not well understood. In acute coronary syndrome without persistent subtheme of the ST segment on ECG (unstable angina, myocardial infarction without subtheme of ST segment), sodium heparin in combination with acetylsalicylic acid reduces the risk of myocardial infarction and mortality. In myocardial infarction with elevation of the ST segment on the ECG, sodium heparin is effective in primary transcutaneous coronary revascularization in combination with glycoprotein IIb / IIIa receptor inhibitors and in thrombolytic therapy with streptokinase (an increase in the frequency of revascularization). In high doses, sodium heparin is effective in pulmonary thromboembolism and venous thrombosis; in small doses, it is effective in preventing venous thromboembolism, including after surgical operations. After intravenous administration, the effect of the drug comes almost immediately, no later than 10-15 minutes and lasts not long - 3-6 hours. After subcutaneous administration, the effect of the drug begins slowly - after 40-60 minutes, but lasts 8 hours. Deficit of antithrombin III in plasma or in the place of thrombosis can reduce the anti-coagulant effect of heparin sodium.
Pharmacokinetics
The maximum concentration (Cmax) after intravenous administration is reached almost immediately, after subcutaneous administration - in 2-4 hours. Communication 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 with plasma proteins). Does not penetrate the placental barrier and into breast milk. Intensively captured by endothelial cells and cells of the mononuclear macrophage system (cells of the reticuloendothelial system), concentrated in the liver and spleen. Metabolized in the liver with the participation of N-desulfamidase and platelet heparinase, which is involved in the metabolism of heparin in the later stages. Participation in platelet factor IV (antiheparin factor) metabolism, as well as the binding of sodium heparin to the macrophage system, explains the rapid biological inactivation and short duration of action.Desulfated molecules under the influence of endoglycosidase of the kidneys are transformed into low molecular weight fragments. TT1 / 2 is 1-6 hours (on average 1.5 hours), increases with obesity, liver and / or kidney failure, decreases with pulmonary embolism, infections, and malignant tumors. Excreted by the kidneys, mainly in the form of inactive metabolites, and only with the introduction of high doses may excretion (up to 50%) in unchanged form. It is not displayed through hemodialysis.
Indications
- prevention and treatment of venous thrombosis (including thrombosis of the 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 disease) - treatment of acute and chronic consumption coagulopathies (including stage I of DIC) - acute coronary syndrome without sustained elevation of the ST segment on an ECG (not mobile angina, myocardial infarction without ST-segment elevation on 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 angioplasty with stenting or without it, and with a high risk of arterial or angioplasty with stenting or without it, and with arterial or coronary angioplasty and treatment of microthrombosis and microcirculation disorders, incl. at gemolitikouremicheskom syndrome, glomerulonephritis (including lupus nephritis) and forced diureze- prevention of blood coagulation during blood transfusion, in extracorporeal circulation systems (extracorporeal circulation during cardiac surgery, hemosorbtion, cytapheresis) and gemodialize- treatment of peripheral venous catheters.
Contraindications
- hypersensitivity to heparin sodium and other components of the drug — a history of heparin-induced thrombocytopenia (with or without thrombosis) - or bleeding (except when the benefits of using sodium heparin outweigh the potential risk) - pregnancy and breast period feeding. With caution to Patients with polyvalent allergies (including bronchial asthma). 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, aortic dissection, cerebral aneurysm — erosive and ulcerative lesions of the gastrointestinal organs, varicose veins of the esophagus during liver cirrhosis, and other diseases of the stomach and small bowel drains, ulcerative colitis, hemorrhoids — diseases of the blood-forming organs and the lymphatic system: leukemia, hemophilia, thrombocytopenia, hemorrhagic diathesis — slaughter Evaniya CNS: hemorrhagic stroke, traumatic brain injury — malignant neoplasms — congenital deficiency of antithrombin III and replacement therapy with antithrombin III drugs (to reduce the risk of bleeding, smaller doses of heparin should be used). Other physiological and pathological conditions: menstruation period, threatening abortion, early postpartum period, severe liver disease with impaired protein-synthetic function, chronic renal failure, recent surgery eye, brain or spinal cord, recent spinal (lumbar) puncture or epidural anesthesia, proliferative diabetic retinopathy, vasculitis, children under 3 years of age (benzyl alcohol may cause toxic and anaphylactoid reactions), old age (older 60 years old, especially women).
Dosage and administration
Heparin is administered subcutaneously, intravenously, bolus or drip. Heparin is prescribed as a continuous intravenous infusion or in the form of regular intravenous injections, as well as subcutaneously (in the abdomen). Heparin should not be administered intramuscularly. The usual place for subcutaneous injections is the anterior-lateral wall of the abdomen (in exceptional cases it is inserted into the upper shoulder or thigh), using a thin needle that should be inserted deep, perpendicular to the fold of skin between the thumb and index finger until the end solution. It is necessary to alternate the injection sites each time (in order to avoid hematoma formation). The first injection should be carried out 1-2 hours before the start of the operation, in the postoperative period it should be administered within 7-10 days, and, if necessary, a longer time.The initial dose of Heparin, administered for therapeutic purposes, is usually 5000 IU and is administered intravenously, after which the treatment is continued using subcutaneous injections or intravenous infusions. Supportive doses are determined depending on the method of administration: - with continuous intravenous infusion, 1000-2000 IU / h (24000-48000 MG / day) are prescribed, diluting Heparin with a 0.9% sodium chloride solution: - with regular intravenous injections, 5000 to 10000 IU are prescribed Heparin every 4-6 hours: - for subcutaneous administration, 15,000 to 20,000 IU are administered every 12 hours or 8,000 to 10,000 IU every 8 hours. Before the introduction of each dose, it is necessary to conduct a study of the clotting time of the blood and / or the activated partial thromboplastin time (LPTT) in order to correct the subsequent dose. When administered intravenously, doses of Heparin are selected so that the APTT is 1.5–2.5 times the control. The anticoagulant effect of Heparin is considered to be optimal if the blood coagulation time is extended by a factor of 2-3 compared with the normal value. APTT and thrombin time increase by 2 times (with the possibility of continuous monitoring of APTT). With subcutaneous administration of small doses (5000 IU 2-3 times a day), it is not necessary to regularly control the APTT for the prevention of thrombus formation, as it slightly increases. Continuous intravenous infusion is the most effective way to use Heparin, better than regular (periodic) injections, as it provides a more stable hypocoagulation and less often causes bleeding. Use of heparin sodium in special clinical situations: Primary percutaneous coronary angioplasty in acute coronary syndrome without ST-segment elevation and in myocardial infarction with ST-segment elevation: sodium heparin is administered intravenously in a dose of 70-100 IU / kg (if you are not planning to use glycoprotein inhibitors llb / IIla receptors) or at a dose of 50-60 MG / kg (when used together with inhibitors of glycoprotein llb / IIla receptors). Thrombolytic therapy for myocardial infarction with ST-segment elevation: sodium heparin is administered intravenously with a bolus dose of 60 IU / kt (maximum dose of 4000 ME), followed by intravenous infusion at a dose of 12 IU / kg (no more than 1000 IU / h) for 24- 48 h. The target APTT level is 50-70 sec, which is 1.5–2.0 times higher than the norm, and the APTT control after 3. 6. 12 and 24 h after the start of therapy.Prevention of thromboembolic complications after surgical interventions using low doses of heparin sodium: sodium heparin is injected subcutaneously, deep into the fold of the abdominal skin. The initial dose is 5000 mg 2 h before the start of the operation. In the postoperative period - 5000 ME every 8-12 hours for 7 days or until the patient’s mobility is fully restored (depending on what comes first). When using low-dose heparin sodium for the prevention of thromboembolic complications, it is not necessary to control aPTT. Use in cardiovascular surgery for operations using the extracorporeal circulation: the initial dose of sodium heparin is at least 150 IU / kg. Next, sodium heparin is injected by continuous intravenous ipfusion at a rate of 15-25 drops / min at 30,000 IU per 1 liter of infusion solution. The total dose is usually 300 IU / kg (if the expected duration of the operation is less than 60 minutes) or 400 IU / kg (if the expected duration of the operation is 60 minutes or more). Application in hemodialysis: the initial dose of sodium heparin is 25-30 IU / kg (or 10,000 IU) intravenously bolus, then continuous infusion of sodium heparin 20,000 IU / 100 ml of 0.9% sodium chloride solution at a rate of 1500-2000 IU / h (unless otherwise indicated in the hemodialysis systems manual). The use of heparin sodium in pediatrics: adequate controlled studies of the use of heparin sodium in children have not been conducted. The presented recommendations are based on clinical experience: the initial dose is 75-100 IU / kg intravenous bolus for 10 minutes, the maintenance dose: children aged 1-3 months - 25-30 IU / kg / h (800 ME / kg / day) , children aged 4-12 months - 25-30 IU / kg / h (700 IU / kg / day), children older than 1 year -18-20 ME / kg / h (500 IU / kg / day) intravenously. The dose of sodium heparin should be selected taking into account blood coagulation parameters (target APTT level 60-85 sec.). The duration of therapy depends on the indications and method of application. For intravenous administration, the optimal duration of treatment is 7-10 days, after which therapy is continued with oral anticoagulants (it is recommended that oral anticoagulants be prescribed starting from day 1 of heparin sodium treatment or from 5 to 7 days, and the use of heparin sodium should be stopped for 4-5 days combined therapy).With extensive thrombosis of the ileal-femoral veins, it is advisable to conduct longer courses of treatment with Heparin.