Heparin-sodium solution 5000IU/ml 5ml ampoules, 5pcs

Composition

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1 ml contains:

Active ingredient:  heparin sodium 5000 ME.

Auxiliary substance:  water for injection up to 1 ml

Pharmacological action

Pharmacotherapy group

Direct-acting anticoagulant

ATX code

B01AB01

Pharmacodynamics :

The mechanism of action of heparin sodium is based primarily on its binding to antithrombin III, which is a natural inhibitor of activated blood clotting factors IIa (thrombin) IXa Xa XIa and XIIa. Heparin sodium binds to antithrombin III and causes conformational changes in its molecule. As a result, the binding of antithrombin III to coagulation factors IIa (thrombin)is accelerated IXa Xa XIa and XIIa and their enzymatic activity is blocked. Binding of sodium heparin to antithrombin III is electrostatic in nature and largely depends on the length and composition of the molecule (for binding of heparin to antithrombin III, a pentasaccharide sequence containing 3-0-sulfated glucosamine is required).

Of greatest importance is the ability of sodium heparin in combination with antithrombin III to inhibit clotting factors IIa (thrombin) and Xa. The ratio of sodium heparin activity against factor Xa to its activity against factor IIa is 09-11.

Heparin sodium reduces blood viscosity reduces vascular permeability stimulated by bradykinin histamine and other endogenous factors and thus prevents the development of stasis. Sodium heparin is able to be sorbed on the surface of endothelial membranes and blood cells, increasing their negative charge, which prevents platelet adhesion and aggregation. Heparin sodium slows down smooth muscle hyperplasia activates lipoprotein lipase and thus has a hypolipidemic 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 (i. e. has an anti-allergic effect). Heparin increases renal blood flow increases the resistance of brain vessels reduces the activity of brain hyaluronidase reduces the activity of surfactant in the lungs suppresses excessive synthesis of aldosterone in the adrenal cortex binds epinephrine modulates the ovarian response to hormonal stimuli increases the activity of parathyroid hormone. As a result of interaction with enzymes, heparin can increase the activity of tyrosine hydroxylase and pepsinogen DNA polymerase and reduce the activity of myosin ATPase pyruvate kinase and pepsin RNA polymerase. The clinical significance of these effects of heparin remains uncertain and poorly understood.

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

In high doses, heparin sodium is effective for pulmonary embolism and venous thrombosis in small doses-it is effective for the prevention of venous thromboembolism, including after surgery.

After intravenous use, the effect of the drug occurs almost immediately no later than 10-15 minutes and does not last long-3-6 hours. After subcutaneous use, the effect of the drug begins slowly-after 40-60 minutes but lasts 8 hours. A deficiency of antithrombin III in blood plasma or at the site of thrombosis can reduce the anticoagulant effect of sodium heparin.

Pharmacokinetics:

The maximum concentration (Cmax) after intravenous use is reached almost immediately after subcutaneous use in 2-4 hours. Plasma protein binding – up to 95% the volume of distribution is very small-006 l / kg (does not leave the vascular bed due to strong binding to plasma proteins). It does not pass through the placenta and into breast milk.

It is intensively absorbed by endothelial cells and cells of the mononuclear-macrophage system (cells of the reticulo-endothelial system) and is concentrated in the liver and spleen.

It is 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 platelet factor IV (antiheparin factor) and the binding of heparin to the macrophage system explain the rapid biological inactivation and short duration of action. Desulfated molecules are converted into low-molecular-weight fragments under the influence of renal endoglycosidase. T1 / 2 – 1-6 hours (on average-15 hours); increases with obesity of the liver and/or kidney failure; decreases with pulmonary embolism infections of malignant tumors.

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

Indications

• prophylaxis and treatment of venous thrombosis (including superficial and deep vein thrombosis of the lower extremities, renal vein thrombosis) and pulmonary embolism;
• prevention and treatment of thromboembolic complications associated with atrial fibrillation;
• prophylaxis and treatment of peripheral arterial embolism (including those associated with mitral valvular heart disease);
• treatment of acute and chronic consumption coagulopathies (including the first stage of DIC);
• acute coronary syndrome without persistent ST-segment elevation on ECG (unstable angina, myocardial infarction without ST-segment elevation on the ECG);
• myocardial infarction with ST-segment elevation during thrombolytic therapy with primary percutaneous coronary revascularization (PTCA with or without stenting) and at high risk of arterial or venous thrombosis and thromboembolism;
• prophylaxis and treatment of macrothrombocytopenia and microcirculatory disorders, including hemolytic uremic syndrome, glomerulonephritis (including lupus nephritis) and forced diuresis;
• prevention of blood clotting when blood transfusion systems extracorporeal circulation (extracorporeal circulation in heart surgery, hemosorption, Tifferet) and in hemodialysis;
• treatment of peripheral venous catheters.

Use during pregnancy and lactation

Sodium heparin does not cross the placental barrier. To date, there are no data indicating the possibility of fetal malformations due to the use of sodium heparin during pregnancy; there are also no results of animal experiments that would indicate the embryo – or fetotoxic effect of sodium heparin. However, there is evidence of an increased risk of preterm labor and spontaneous abortions associated with bleeding. It is necessary to take into account the likelihood of complications when using heparin sodium in pregnant women with concomitant diseases, as well as in pregnant women receiving additional treatment.

Daily use of high doses of sodium heparin for more than 3 months may increase the risk of osteoporosis in pregnant women. Therefore, continuous use of high doses of sodium heparin should not exceed 3 months. Epidural anesthesia should not be used in pregnant women who are undergoing anticoagulant therapy. Anticoagulant therapy is contraindicated if there is a risk of bleeding, for example, with a threatened abortion.

Heparin sodium is not excreted in breast milk. Daily use of high doses of sodium heparin for more than 3 months may increase the risk of osteoporosis in nursing women.

If it is necessary to apply it during the specified periods, it is necessary to correlate the benefit/risk.

Contraindications

-Hypersensitivity to heparin and other components of the drug.

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

– Bleeding (except in cases where the benefits of using heparin sodium outweigh the potential risk).

– Heparin sodium in a therapeutic dose should not be prescribed if it is not possible to provide regular laboratory monitoring of blood clotting.

– Pregnancy and lactation period.

With caution:

Patients with polyvalent allergies (including bronchial asthma).

For pathological conditions associated with an increased risk of bleeding such as:

– Diseases of the cardiovascular system: acute and subacute infectious endocarditis severe uncontrolled arterial hypertension dissection of the aorta aneurysm of brain vessels.

– Erosive and ulcerative lesions of the gastrointestinal tract varicose veins of the esophagus in cirrhosis of the liver and other diseases long-term use of gastric and small intestinal drains ulcerative colitis hemorrhoids.

– Diseases of the hematopoietic organs of the blood and lymphatic system: leukemia hemophilia thrombocytopenia hemorrhagic diathesis.

– Diseases of the central nervous system: hemorrhagic stroke, traumatic brain injury.

– Malignant neoplasms.

– Congenital antithrombin III deficiency and antithrombin III replacement therapy (lower doses of heparin should be used to reduce the risk of bleeding).

Other physiological and pathological conditions: menstrual period risk of miscarriage early postpartum period severe liver diseases with impaired protein-synthetic function chronic renal failure recently undergone surgery on the eyes of the brain or spinal cord recently performed spinal (lumbar) puncture or epidural anesthesia proliferative diabetic retinopathy vasculitis elderly (over 60 years, especially women).

Side effects

Allergic reactions: hyperemia of the skin drug fever urticaria rhinitis pruritus and hot sensation in the soles of the feet 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 heparin treatment, transient thrombocygopenia may sometimes occur with platelet counts ranging 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 blood clot formation syndrome) can occur, sometimes with a fatal outcome. This complication should be assumed if the number of platelets decreases below 80×109/l or more than 50% of the initial level, the use 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 and stroke.

Long-term use: osteoporosis spontaneous bone fractures soft tissue calcification hypoaldosteronism transient alopecia priapism.

During heparin therapy, changes in blood biochemical parameters may occur (an increase in the activity of “hepatic” transaminases of free fatty acids and thyroxine in blood plasma; hyperkalemia; recurrent hyperlipidemia due to the withdrawal of sodium heparin; a false increase in blood glucose levels and an error in the results of the bromosulfal and new test).

Local reactions: irritation pain hyperemia hematoma and ulceration at the injection site bleeding.

Bleeding: typical-from the gastrointestinal tract and urinary tract at the injection site in areas under pressure from surgical wounds; hemorrhages in various organs (including the adrenal glands yellow body retroperitoneal space).

If any of the side effects listed in the instructions get worse or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

Pharmaceutical interaction: sodium heparin solution is compatible only with 09% sodium chloride solution. Alteplase amikacin sulfate amiodarone ampicillin sodium benzylpenicillin sodium ciprofloxacin cytarabine dacarbazine danorubicin diazepam dobutamine doxorubicin hydrochloride droperidol erythromycin gentamicin haloperidol sulfate lactate hyaluronidase sodium hydrocortisone succinate dextrose fat emulsions idarubicin kanamycin sulfate methicillin sodium netilmycin sulfate opioids oxytetracycline hydrochloride polymyxin B promazine sulfate promethazine hydrochloride streptomycin sulfate sulfafurazole diethanolamine tetracycline hydrochloride tobramycin sulfate cephalotin sodium cephaloridin vancomycin vinblastine hydrochloride labetalol sulfate nicardipine hydrochloride.

Pharmacokinetic interaction: heparin sodium displaces phenytoin quinidine propranolol and benzodiazepine derivatives from the sites of their binding to plasma proteins, which can lead to increased pharmacological action of these drugs. Heparin sodium binds to and is inactivated by protamine sodium, alkaline-reacting polypeptides, and tricyclic antidepressants.

Pharmacodynamic interaction: the anticoagulant effect of heparin sodium is enhanced when used simultaneously with other drugs that affect hemostasis, including antiplatelet drugs (acetylsalicylic acid clopidogrel prasugrel ticlopidine dipyridamole) indirect anticoagulants (warfarin phenylin syncumar) thrombolytic drugs (alteplase streptokinase urokinase) nonsteroidal anti-inflammatory drugs (including phenylbutazone ibuprofen Indometacin diclofenac) glucocorticosteroids and dextran, which increases the risk of bleeding. In addition the anticoagulant effect of sodium heparin may be enhanced when combined with hydroxychloroquine sulfinpyrazone probenecid etacric acid cytostatics cefamandol cefotetan valproic acid propylthiouracil.

The anticoagulant effect of sodium heparin is reduced when used concomitantly with ACTH antihistamines ascorbic acid ergot alkaloids nicotine nitroglycerin cardiac glycosides thyroxine tetracycline and quinine.

Heparin sodium may reduce the pharmacological effects of the adrenocorticotropic hormone glucocorticosteroids and insulin.

How to take, course of use and dosage

Heparin is given as a continuous intravenous infusion or as subcutaneous or intravenous injections.

The initial dose of heparin administered for therapeutic purposes is 5000 IU and is administered intravenously after which treatment continues using subcutaneous injections or intravenous nifusions.

Maintenance doses are determined depending on the method of use:

– with continuous intravenous infusion to introduce a dose of 1000-2000 IU/h (24000-48000 IU/day) breeding heparin at 09% solution of sodium chloride or 5% or 10% glucose solution or sodium chloride solution 045% glucose and 25% or ringer’s solution;

– regular intravenous injections administered 5,000-10,000 IU of heparin every 4-6 hours;

– at subcutaneous injection administered every 12 hours for 15000-20000IU or every 8 hours for 8000-10000 ME.

Before each dose is administered, blood clotting time and/or activated partial thromboplastin time (APTT) should be evaluated in order to correct the subsequent dose. Subcutaneous injections are preferably performed in the area of the anterior abdominal wall, as an exception, you can use other injection sites (shoulder hip).

Repeated use of sodium heparin to the sites of previous injections is undesirable. Before injection, it is necessary to remove drops of the solution from the outer surface of the needle.

Doses of heparin sodium for intravenous use are selected so that the APTT is 15-25 times higher than the control one.

The anticoagulant effect of heparin is considered optimal if the blood clotting time is extended by 2-3 times compared to the normal APTT index and the thrombin time is increased by 2 times (if continuous APTT monitoring is possible).

When preventing thrombosis in the postoperative period, the first injection should be performed 1-2 hours before the operation; in the postoperative period, it should be administered within 7-10 days and, if necessary, for a longer time.

Use of heparin sodium in special clinical situations

Primary percutaneous coronary intervention in acute coronary syndrome without ST-segment elevation and myocardial infarction with ST-segment elevation:

heparin sodium is administered intravenously bolus at a dose of 70-100 U/kg (if you do not plan inhibitors of glycoprotein IIb/IIIa receptors) or at a dose of 50-60 U/kg (when used together with inhibitors of glycoprotein IIb/IIIa receptors).

Thrombolytic therapy for ST-segment elevation myocardial infarction: heparin sodium is administered by intravenous bolus at a dose of 60 U / kg (maximum dose of 4000 U), followed by intravenous infusion at a dose of 12 U / kg (no more than 1000 U / h) for 24-48 hours. The target APTT level is 50-70 seconds or 1.5-2.0 times higher than normal; APTT control is 3,6,12 and 24 hours after the start of therapy.

Prevention of thromboembolic complications after surgery using low-dose sodium heparin: subcutaneously deep into the fold of the abdominal skin. The initial dose is 5000 IU 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 fully restored (whichever comes first). When using sodium heparin in low doses to prevent thromboembolic complications, it is not necessary to monitor APTT. Application in cardiovascular surgery during operations using the extracorporeal circulation system: the initial dose is not less than 150 IU/kg. Further, sodium heparin is administered by continuous intravenous infusion at a rate of 15-25 drops / min at 30,000IU per 1 liter of infusion solution. The total dose is usually 300 IU / kg (if the expected duration of surgery is less than 60 minutes) or 400 IU / kg (if the expected duration of the operation is 60 minutes or more).

Use in hemodialysis: The initial dose is 25-30 U / kg (or 10,000 U) by intravenous bolus followed by a continuous infusion of 20000 IU/100 mg sodium chloride solution at a rate of 1500-2000 U / h (unless otherwise specified in the guidelines for the use of hemodialysis systems). The dose of heparin sodium should be selected based on blood clotting parameters (target APTT level of 60-85 seconds).

The use of sodium heparin in pediatrics: Adequate controlled studies 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.Maintenance dose: children aged 1-3 months-25-30 U / kg / h (800 DB / kg / day) children aged 4-12 months-25-30 U/kg / h (700 U/kg / day) children over 1 year-18-20 U/kg / h (500 U/kg/day) intravenously.

Overdose

Symptoms: signs of bleeding.

Treatment: for minor bleeding caused by an overdose of heparin, it is sufficient to stop using it. In case of extensive bleeding, excess heparin is neutralized with protamine sulfate (1 mg of protamine sulfate per 100 IU of heparin).1% protamine sulfate solution is administered intravenously very slowly. No more than 50 mg (5 ml) of protamine sulfate should be administered every 10 minutes. Given the rapid metabolism of heparin sodium, the required dose of protamine sulfate decreases over time. To calculate the required dose of protamine sulfate, we can assume that T1 / 2 of sodium heparin is 30 minutes. When using protamine, severe anaphylactic reactions with a fatal outcome were noted, and therefore the drug should be administered only in a department equipped for emergency medical care in anaphylactic shock. Hemodialysis is ineffective.

Special instructions

High-dose treatment is recommended in a hospital setting. Platelet count monitoring should be performed before starting treatment on the first day of treatment and at short intervals during the entire period of use of heparin, especially between 6 and 14 days after the start of treatment. Treatment should be stopped immediately if there is a sharp decrease in platelet count (see “Side effect”).

A sharp decrease in platelet count requires further investigation to detect heparin-induced immune thrombocytopenia. If this is the case, the patient should be advised that he should not be prescribed heparin in the future (even low-molecular-weight heparin). If there is a high probability of heparin-induced immune thrombocytopenia, heparin should be discontinued immediately.

If heparin-induced thrombocytopenia develops in patients receiving heparin for thromboembolic disease or in the case of thromboembolic complications, other antithrombotic agents should be used. Patients with heparin-induced immune thrombocytopenia (white blood clot formation syndrome) should not undergo hemodialysis with heparinization. If necessary, they should use alternative methods of treating kidney failure.

To avoid overdose, it is necessary to constantly monitor clinical symptoms indicating possible bleeding (bleeding of the mucous membranes, hematuria, etc. ). In people who do not respond to heparin or require high doses of heparin, it is necessary to monitor the level of antithrombin III.

Resistance to sodium heparin is often observed in fever thrombosis thrombophlebitis infectious diseases myocardial infarction malignant neoplasms as well as after surgical interventions and with antithrombin III deficiency. In such situations, more thorough laboratory monitoring (APTT control) is required.

Although heparin sodium does not cross the placental barrier and is not detected in breast milk, when prescribed at therapeutic doses, pregnant women and breast-feeding mothers should be carefully monitored.

Special care should be taken within 36 hours after delivery.

Appropriate control laboratory tests (blood clotting time activated partial thromboplastin time and thrombin time) should be performed.

In women over 60 years of age, heparin may increase bleeding, and therefore the dose of sodium heparin in this category of patients should be reduced.

When using heparin in patients with arterial hypertension, blood pressure should be constantly monitored.

Before starting therapy with heparin sodium, a coagulogram study should always be performed, except for the use of low doses.

In patients who are being transferred to oral anticoagulant therapy, heparin sodium should be continued until the results of blood clotting time and APTT are within the therapeutic range. Intramuscular injections should be excluded when prescribing sodium heparin for medicinal purposes. Puncture biopsies of infiltration and epidural anesthesia and diagnostic lumbar punctures should also be avoided if possible.

If massive bleeding occurs, the sodium heparin should be discontinued and the coagulogram parameters examined. If the test results are within the normal range, then the probability of developing this bleeding due to the use of sodium heparin is minimal. Changes in the coagulogram tend to normalize after heparin withdrawal.

Physical and chemical stability after dilution of heparin in the above infusion solutions is maintained for 48 hours at room temperature (25 ± 2 °C). If the drug is not used immediately, it can be used no later than 24 hours after dilution, and it is allowed to store it during this period at a temperature of 2 to 8 °C only if aseptic conditions are observed during its dilution.

Influence on the ability to drive vehicles and mechanisms:

Studies evaluating the effect of heparin on the ability to drive vehicles and engage in potentially dangerous activities have not been conducted.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 4 years.

Do not use after the expiration date indicated on the package.

Active ingredient

Sodium Heparin

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection