Heparin sodium solution for intravenous and subcutaneous administration of 5000IU / ml, 5ml No. 5

Thrombosis, thromboembolism (prevention and treatment), prevention of blood clotting (in cardiovascular surgery), coronary thrombosis, disseminated intravascular coagulation, postoperative period in patients with a history of thromboembolism.
Prevention of blood clotting during operations using extracorporeal blood circulation methods.

Heparin is given as a continuous intravenous infusion or as a subcutaneous or intravenous injection.
The initial dose of medicinal heparin is 5000 IU and is given intravenously, after which treatment is continued using subcutaneous injections or intravenous infusions.
Maintenance doses are determined depending on the method of administration:

• with continuous intravenous infusion, administer at a dose of 15 IU / kg of body weight per hour, diluting heparin in 0.9% NaCl solution;

• with regular intravenous injections, 5000-10000 IU of heparin is prescribed every 4-6 hours;

• for subcutaneous administration, it is administered every 12 hours at 15000-20000 ME or every 8 hours at 8000-10000 ME.

Before the introduction of each dose, it is necessary to conduct a study of blood clotting time and / or activated partial thromboplastin time (APTT) in order to adjust the subsequent dose. Subcutaneous injections are preferably performed in the region of the anterior abdominal wall; as an exception, other injection sites (shoulder, thigh) can be used.
The anticoagulant effect of heparin is considered optimal if the blood clotting time is 2-3 times longer than the normal value, the activated partial thromboplastin time (APTT) and thrombin time are doubled (with the possibility of continuous APTT control).
For patients in extracorporeal circulation, heparin is prescribed at a dose of 150-400 IU / kg of body weight or 1500-2000 IU / 500 ml of preserved blood (whole blood, erythrocyte mass).
For patients on dialysis, dose adjustment is carried out according to the results of the coagulogram.
The drug is administered intravenously to children: at the age of 1-3 months - 800 IU / kg / day, 4-12 months - 700 IU / kg / day, over 6 years old - 500 IU / kg / day under the control of APTT (activated partial thromboplastin time ).

1 liter of solution contains:
active substance: sodium heparin - 5,000,000 IU
excipients : benzyl alcohol, sodium chloride, water for injection.

Hypersensitivity to heparin, diseases accompanied by increased bleeding (hemophilia, thrombocytopenia, vasculitis, etc.), bleeding, cerebral aneurysm, dissecting aortic aneurysm, hemorrhagic stroke, antiphospholipid syndrome, trauma, especially craniocerebral ulcer), erosive, tumors and polyps of the gastrointestinal tract (gastrointestinal tract); subacute bacterial endocarditis; severe violations of liver and kidney function; cirrhosis of the liver, accompanied by varicose veins of the esophagus, severe uncontrolled arterial hypertension; hemorrhagic stroke; recent surgery on the brain and spine, eyes, prostate, liver, or biliary tract; conditions after spinal cord puncture, proliferative diabetic retinopathy; diseases,accompanied by a decrease in blood clotting time; menstrual period, threatening miscarriage, childbirth (including recent), pregnancy, lactation; thrombocytopenia; increased vascular permeability; pulmonary bleeding.
With caution
Persons suffering from polyvalent allergies (including bronchial asthma), arterial hypertension, dental procedures, diabetes mellitus, endocarditis, pericarditis, IUD (intrauterine contraception), active tuberculosis, radiation therapy, liver failure, chronic renal failure (chronic renal failure ), old age (over 60 years old, especially women).

Trade name of the drug:

Heparin

International non-proprietary name:

Heparin sodium

Dosage form:

solution for intravenous and subcutaneous administration

Composition:

1 liter of solution contains:
active substance: sodium heparin - 5,000,000 IU
excipients : benzyl alcohol, sodium chloride, water for injection.

Description:

Transparent colorless or light yellow liquid.

Pharmacotherapeutic group:

direct anticoagulant

ATX code:

¬01ј¬01

Pharmacological properties

Direct-acting anticoagulant, belongs to the group of medium-molecular heparins, slows down the formation of fibrin. The anticoagulant effect is found in vitro and in vivo, occurs immediately after intravenous administration.
The mechanism of action of heparin is based primarily on its binding to antithrombin III, an inhibitor of activated blood coagulation factors: thrombin, IXa, Xa, XIa, XIIa (the ability to inhibit thrombin and activated factor X is especially important).
Increases renal blood flow; increases the resistance of blood vessels in the brain, reduces the activity of cerebral hyaluronidase, activates lipoprotein lipase and has a hypolipidemic effect.
Reduces the activity of surfactant in the lungs, inhibits excessive synthesis of aldosterone in the adrenal cortex, binds adrenaline, modulates the response of the ovaries to hormonal stimuli, increases the activity of parathyroid hormone. As a result of interaction with enzymes, it can increase the activity of brain tyrosine hydroxylase, pepsinogen, DNA polymerase and reduce the activity of myosin ATPase, pyruvate kinase, RNA polymerase, and pepsin.
In patients with coronary artery disease (ischemic heart disease) (in combination with ASA (acetylsalicylic acid) reduces the risk of acute thrombosis of the coronary arteries, myocardial infarction and sudden death. Reduces the frequency of repeated heart attacks and mortality in patients who have had myocardial infarction.
In high doses it is effective for pulmonary embolism and venous thrombosis, in small doses - for the prevention of venous thromboembolism, incl. after surgery.
With intravenous administration, blood coagulation slows down almost immediately, with intramuscular administration - after 15-30 minutes, with subcutaneous administration - after 20-60 minutes, after inhalation the maximum effect is in a day; the duration of the anticoagulant effect, respectively, is 4-5, 6, 8 hours and 1-2 weeks, the therapeutic effect - prevention of thrombus formation - lasts much longer.
Deficiency of antithrombin III in plasma or at the site of thrombosis can reduce the antithrombotic effect of heparin.

Pharmacokinetics
After subcutaneous administration of TCmax - 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). Does not penetrate the placenta and breast milk. It is intensively captured by endothelial cells and cells of the mononuclear-macrophage system (cells of the RES (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 at later stages. Participation in the metabolism of heparin at later stages. platelet factor IV (antiheparin factor), as well as the binding of heparin to the macrophage system, explain the rapid biological inactivation and short duration of action.Desulfated molecules under the influence of kidney endoglycosidase are converted into low molecular weight fragments. T? - 1-6 hours (average 1.5 hours); increases with obesity, hepatic and / or renal failure; decreases with pulmonary embolism, 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. Not excreted by hemodialysis.

Indications for use

Thrombosis, thromboembolism (prevention and treatment), prevention of blood clotting (in cardiovascular surgery), coronary thrombosis, disseminated intravascular coagulation, postoperative period in patients with a history of thromboembolism.
Prevention of blood clotting during operations using extracorporeal blood circulation methods.

Contraindications

Hypersensitivity to heparin, diseases accompanied by increased bleeding (hemophilia, thrombocytopenia, vasculitis, etc.), bleeding, cerebral aneurysm, dissecting aortic aneurysm, hemorrhagic stroke, antiphospholipid syndrome, trauma, especially craniocerebral ulcer), erosive, tumors and polyps of the gastrointestinal tract (gastrointestinal tract); subacute bacterial endocarditis; severe violations of liver and kidney function; cirrhosis of the liver, accompanied by varicose veins of the esophagus, severe uncontrolled arterial hypertension; hemorrhagic stroke; recent surgery on the brain and spine, eyes, prostate, liver, or biliary tract; conditions after spinal cord puncture, proliferative diabetic retinopathy; diseases,accompanied by a decrease in blood clotting time; menstrual period, threatening miscarriage, childbirth (including recent), pregnancy, lactation; thrombocytopenia; increased vascular permeability; pulmonary bleeding.
With caution
Persons suffering from polyvalent allergies (including bronchial asthma), arterial hypertension, dental procedures, diabetes mellitus, endocarditis, pericarditis, IUD (intrauterine contraception), active tuberculosis, radiation therapy, liver failure, chronic renal failure (chronic renal failure ), old age (over 60 years old, especially women).

Method of administration and dosage

Heparin is given as a continuous intravenous infusion or as a subcutaneous or intravenous injection.
The initial dose of medicinal heparin is 5000 IU and is given intravenously, after which treatment is continued using subcutaneous injections or intravenous infusions.
Maintenance doses are determined depending on the method of administration:

• with continuous intravenous infusion, administer at a dose of 15 IU / kg of body weight per hour, diluting heparin in 0.9% NaCl solution;

• with regular intravenous injections, 5000-10000 IU of heparin is prescribed every 4-6 hours;

• for subcutaneous administration, it is administered every 12 hours at 15000-20000 ME or every 8 hours at 8000-10000 ME.

Before the introduction of each dose, it is necessary to conduct a study of blood clotting time and / or activated partial thromboplastin time (APTT) in order to adjust the subsequent dose. Subcutaneous injections are preferably performed in the region of the anterior abdominal wall; as an exception, other injection sites (shoulder, thigh) can be used.
The anticoagulant effect of heparin is considered optimal if the blood clotting time is 2-3 times longer than the normal value, the activated partial thromboplastin time (APTT) and thrombin time are doubled (with the possibility of continuous APTT control).
For patients in extracorporeal circulation, heparin is prescribed at a dose of 150-400 IU / kg of body weight or 1500-2000 IU / 500 ml of preserved blood (whole blood, erythrocyte mass).
For patients on dialysis, dose adjustment is carried out according to the results of the coagulogram.
The drug is administered intravenously to children: at the age of 1-3 months - 800 IU / kg / day, 4-12 months - 700 IU / kg / day, over 6 years old - 500 IU / kg / day under the control of APTT (activated partial thromboplastin time ).

Side effect

Allergic reactions: flushing of the skin, drug fever, urticaria, rhinitis, pruritus and a feeling of heat in the soles, bronchospasm, collapse, anaphylactic shock.
Other potential side effects include dizziness, headache, nausea, decreased appetite, vomiting, diarrhea, joint pain, increased blood pressure, and eosinophilia.
At the beginning of treatment with heparin, transient thrombocytopenia (6% of patients) may sometimes occur with a platelet count in the range from 80 x 109 / l to 150 x 109 / l. Usually, this situation does not lead to the development of complications and treatment with heparin can be continued. In rare cases, severe thrombocytopenia (white thrombus formation syndrome), sometimes fatal, may occur. This complication should be assumed in the case of a decrease in the number of platelets below 80x109 / l or more than 50% of the initial level, the administration of heparin in such cases is urgently stopped. Patients with severe thrombocytopenia may develop consumption coagulopathy (depletion of fibrinogen stores).
Against the background of heparin-induced thrombocytopenia: skin necrosis, arterial thrombosis, accompanied by the development of gangrene, myocardial infarction, stroke.
With prolonged use: osteoporosis, spontaneous bone fractures, soft tissue calcification, hypoaldosteronism, transient alopecia.
Against the background of heparin therapy, changes in blood biochemical parameters can be observed (an increase in the activity of 'hepatic' transaminases, free fatty acids and thyroxine in the blood plasma; reversible potassium retention in the body; false decrease in cholesterol levels; false increase in blood glucose and an error in the results of the bromsulfalein test) ...
Local reactions: irritation, pain, hyperemia, hematoma and ulceration at the injection site, bleeding.
Bleeding: typical - from the gastrointestinal tract (gastrointestinal tract) and urinary tract, at the injection site, in areas exposed to pressure, from surgical wounds; hemorrhages in various organs (including adrenal glands, corpus luteum, retroperitoneal space).

Overdose

Symptoms : signs of bleeding.
Treatment : for minor bleeding caused by an overdose of heparin, it is enough to stop using it. With extensive bleeding, excess heparin is neutralized with protamine sulfate (1 mg protamine sulfate per 100 IU of heparin). It should be borne in mind that heparin is quickly excreted, and if protamine sulfate is prescribed 30 minutes after the previous dose of heparin, only half of the required dose should be administered; the maximum dose of protamine sulfate is 50 mg. Hemodialysis is ineffective.

Interaction with other medicinal products

Before any surgical interventions using heparin, oral anticoagulants (for example, dicoumarins) and antiplatelet agents (for example, acetylsalicylic acid, dipyridamole) should be canceled at least 5 days in advance, since they can increase bleeding during surgery or in the postoperative period.
The simultaneous use of ascorbic acid, antihistamines, digitalis or tetracyclines, ergot alkaloids, nicotine, nitroglycerin (intravenous administration), thyroxine, ACTH (adenocorticotropic hormone), alkaline amino acids and polypeptides, protamine can reduce the effect of heparin. Dextran, phenylbutazone, indomethacin, sulfinpyrazone, probenecid, intravenous administration of ethacrynic acid, penicillins and cytostatics can potentiate the action of heparin. Heparin replaces phenytoin, quinidine, propranolol, benzodiazepines and bilirubin at their protein binding sites. Mutual decrease in effectiveness occurs with the simultaneous use of tricyclic antidepressants, because they can bind to heparin.
Due to the potential for precipitation of the active ingredients, heparin should not be mixed with other drugs.

special instructions

Treatment with large doses is recommended in a hospital setting.
Monitoring the number of platelets should be carried out before starting treatment, on the first day of treatment and at short intervals throughout the period of heparin administration, especially between 6 and 14 days after the start of treatment. You should immediately stop treatment with a sharp decrease in the number of platelets (see 'Side effects').
The sharp decrease in platelet count requires further investigation to identify heparin-induced immune thrombocytopenia.
If this is the case, the patient should be advised that heparin should not be prescribed in the future (even low molecular weight heparin). If there is a high likelihood of heparin-induced immune thrombocytopenia, heparin should be withdrawn immediately.
If heparin-induced thrombocytopenia develops in patients receiving heparin for thromboembolic disease or if thromboembolic complications develop, other antithrombotic agents should be used.
Patients with heparin-induced immune thrombocytopenia (white thrombus formation syndrome) should not undergo hemodialysis with heparinization. If necessary, they should use alternative treatments for kidney failure.
To avoid overdose, it is necessary to constantly monitor clinical symptoms indicating possible bleeding (bleeding of the mucous membranes, hematuria, etc.). In individuals who do not respond to heparin or require high doses of heparin, it is necessary to control the level of antithrombin III.
Although heparin does not cross the placental barrier and is not detected in breast milk, when administered in therapeutic doses, pregnant women and breastfeeding mothers should be closely monitored.
Particular care should be taken within 36 hours of delivery. It is necessary to conduct appropriate control laboratory tests (blood coagulation time, activated partial thromboplastin time and thrombin time).
In women over 60, heparin can increase bleeding.
When using heparin in patients with arterial hypertension, blood pressure should be constantly monitored.
Before starting heparin therapy, a coagulogram study should always be performed, with the exception of the use of low doses.
Patients who are switched to oral anticoagulant therapy should be continued with heparin until clotting time and activated partial thromboplastin time (APTT) are within the therapeutic range.
Intramuscular injections should be avoided when prescribing heparin for medicinal purposes. Puncture biopsies, infiltration and epidural anesthesia, and diagnostic lumbar punctures should also be avoided whenever possible.
If massive bleeding occurs, heparin should be discontinued and coagulogram indicators should be examined. If the test results are within normal limits, then the likelihood of developing this bleeding due to the use of heparin is minimal; Changes in the coagulogram tend to normalize after discontinuation of heparin.
Protamine sulfate is a specific antidote to heparin. One ml of protamine sulfate neutralizes 1000 IU of heparin. Doses of protamine should be adjusted depending on the results of the coagulogram, since an excessive amount of this drug itself can provoke bleeding.

Release form

Solution for intravenous and subcutaneous administration of 5000 IU / ml, 5 ml in ampoules or vials.
5 ml in neutral glass ampoules or 5 ml in neutral glass vials. 5 ampoules in a blister strip packaging. One blister strip with instructions for use, a knife or an ampoule scarifier is placed in a cardboard box. 30 or 50 blisters with foil with 15 or 25 instructions for use, respectively, with knives or ampoule scarifiers (for hospital) are placed in a cardboard box or in a corrugated cardboard box.
When packing ampoules with notches, rings or break points, ampoule knives or scarifiers are not inserted.
5 vials in a blister strip packaging. One blister strip packaging with instructions for use in a cardboard box. 30 or 50 blisters with foil with 15 or 25 instructions for use, respectively (for a hospital), are placed in a cardboard box or in a corrugated cardboard box.

Storage conditions

List B. In the dark place at a temperature of 12-15 ? C.
Keep out of the reach of children.

Shelf life

3 years. Do not use after the expiration date printed on the package.

Vacation conditions

On prescription.