Heparin sodium - instructions for use, dose, side effects, contraindications

Active substance:
heparin sodium (in terms of dry matter)	5000 ME	25000 ME
Excipients:
benzyl alcohol	10 mg	50 mg
sodium chloride	3 mg	15 mg
hydrochloric acid, concentrated or sodium hydroxide	to pH 5.5-8.0	to pH 5.5-8.0
water for injections	up to 1 ml	up to 5 ml

Description:Colorless or light yellow transparent solution

Pharmacotherapeutic group:Anticoagulant means of direct action

ATX: & nbsp

B.01.A.B.01 Heparin

Pharmacodynamics:

Anticoagulant direct action, refers to the group of medium-molecular heparins, slows the formation of fibrin. Anticoagulant effect is detected in vitro and in vivo, occurs immediately after intravenous administration.

The mechanism of action of sodium heparin is based, first of all, on its binding to antithrombin III - an inhibitor of activated blood coagulation factors: Na (thrombin), IXa, Ha, XIa, XIIbut (especially important is the ability to inhibit thrombin and activated factor X). Sodium Heparin is bound by antithrombin III and causes conformational changes in its molecule. As a result, binding of antithrombin III to blood coagulation factors is accelerated IIa (thrombin), IXa, Ha, XIa. XIIa and their enzymatic activity is blocked. The binding of sodium heparin to antithrombin III is of an electrostatic nature and largely depends on the length and composition of the molecule (for binding of sodium 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 to factor Xa to its activity against factor IIbut is 0.9-1.1. Sodium Heparin reduces blood viscosity, reduces vascular permeability, stimulated bradykinin, histamine and other endogenous factors, and thus prevents the development of stasis. Sodium Heparin can sorb on the surface of membranes of the endothelium and blood cells, increasing their negative charge, which prevents adhesion and aggregation of platelets. Sodium Heparin slows hyperplasia of smooth muscles, 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, interferes with the cooperation of lymphocytes and the formation of immunoglobulins, binds histamine, serotonin (i.e., has anti-allergic effect). Sodium Heparin increases renal blood flow; increases the resistance of cerebral 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 the activity of parathyroid hormone. As a result of interaction with enzymes heparin sodium can increase the activity of tyrosine hydroxylase of the brain, 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 segment elevation ST on ECG (unstable angina, myocardial infarction without persistent elevation of the segment ST) heparin sodium in combination with acetylsalicylic acid reduces the risk of myocardial infarction and reduces mortality. With myocardial infarction with a segment elevation ST on the ECG heparin sodium is effective in primary percutaneous coronary revascularization in combination with glycoprotein inhibitors IIb/IIIbut receptors and with thrombolytic therapy with streptokinase (an increase in the frequency of revascularization).

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

After intravenous administration of sodium heparin action occurs almost immediately, no later than 10-15 minutes and lasts long - 3-6 hours after subcutaneous administration of heparin sodium action begins slowly -. Over 40-60 min, but lasts 8 hours.

Deficiency of antithrombin III in plasma or in the place of thrombosis can reduce the antithrombotic effect of heparin sodium.

Pharmacokinetics:

After intravenous administration, the maximum concentration (FROMmOh) is achieved almost immediately, after a subcutaneous injection - after 2-4 hours. The connection with plasma proteins is up to 95%, the volume of distribution is very low and is 0.06 l / kg (does not leave the vascular bed due to strong binding to plasma proteins).

Heparin 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), it is concentrated in the liver and spleen. Metabolised in the liver with participation N-desulfamidase and heparinase of platelets involved 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 of heparin (T1 / 2) is 1-6 hours (an average of 1.5 hours); T1 / 2 increases with obesity, hepatic and / or renal insufficiency; decreases with thromboembolism of the pulmonary artery, infectious diseases, malignant neoplasms. It is excreted by the kidneys, mainly in the form of inactive metabolites. With the introduction of high doses, it is possible to excrete (up to 50%) unchanged. It is not excreted by hemodialysis.

Indications:

Prevention and treatment of venous thrombosis (including thrombosis of surface and deep veins of the lower extremities; thrombosis of the renal veins) and thromboembolism of the pulmonary artery;

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 persistent elevation of the segment ST on ECG (unstable angina, myocardial infarction without segment elevation ST on the ECG);

myocardial infarction with segment elevation ST: 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;

prevention and therapy of microthrombogenesis and microcirculatory disorders, including hemolytic-uremic syndrome; glomerulonephritis (including lupus nephritis) and in forced diuresis:

prevention of blood clotting in blood transfusion, extracorporeal circulation systems (extracorporeal circulation in heart surgery, hemosorption, cytaresis) and hemodialysis;

treatment of peripheral venous catheters.

Contraindications:

Increased sensitivity to heparin or other components that make up the drug.

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

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

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

Newborns, especially premature babies or those with low body weight (since benzyl alcohol is part of the drug).

Pregnancy and the period of breastfeeding.

Carefully:

Patients with a multivalent allergy in history (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, exfoliation of the aorta, aneurysm of the cerebral vessels;

erosive and ulcerative lesions of the gastrointestinal tract (GI tract) (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 the blood and 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 preparations III (to reduce the risk of bleeding it is necessary to use smaller doses of heparin).

Other physiological and pathological conditions: menstruation, threatened abortion, early postpartum period, severe liver disease with impaired belkovosinteticheskoy function, chronic renal failure, has recently undergone surgical intervention on the eyes, brain or spinal cord, recent spinal (lumbar) puncture or epidural anesthesia , proliferative diabetic retinopathy, vasculitis, children under 3 years (part of the benzyl alcohol may cause oksicheskih and anaphylactoid reactions), advanced age (over 60 years, especially the women). The use of heparin sodium is possible in cases where the expected benefit of therapy outweighs the potential risk.

Pregnancy and lactation:

Heparin sodium does not penetrate the placental barrier. So far, no data indicating the possibility of fetal malformations due to the use of sodium heparin during pregnancy, also lack the results of experiments on animals, which would indicate embryo- or foetotoxic action of sodium heparin. However, there is evidence of an increased risk of preterm labor and spontaneous abortion 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 heparin sodium for more than 3 months may increase the risk of osteoporosis in nursing women.

If necessary, during the specified periods, it is necessary to use other preparations of heparin sodium, which do not contain benzyl alcohol as an auxiliary.

Dosing and Administration:

Heparin is administered subcutaneously, intravenously (bolus or drip).

Heparin is prescribed in the form of continuous intravenous infusion or in the form of regular intravenous injections, as well as subcutaneously (in the abdomen).

Heparin sodium can not be administered intramuscularly because of the risk of developing intramuscular hematomas.

Subcutaneous injections are preferably performed in the region of the anterolateral wall of the abdomen (in exceptional cases, inserted into the upper region of the shoulder or thigh), using a thin needle,which should be injected deeply, perpendicularly, into the fold of the skin held between the thumb and forefinger until the end of the solution. Each time, alternate injection sites (to avoid the formation of a hematoma). The first injection should be performed 1-2 hours before the operation, in the postoperative period - administered within 7-10 days, and if necessary - for a longer time.

The initial dose of heparin sodium, administered for medicinal purposes, is usually 5000 ME and is administered intravenously, after which the treatment is continued using subcutaneous injections or intravenous infusions.

Supporting doses are determined depending on the method of application:

with continuous intravenous infusion, appoint 1000-2000 IU / h (24000-48000 IU / day), diluting heparin with 0.9% sodium chloride solution; with regular intravenous injections appoint 5000-10000 ME heparin every 4-6 hours;

when administered subcutaneously every 12 hours to 15,000-20,000 ME or every 8 hours to 8000-10000 ME.

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 1.5-2.5 times higher than the control values or if the patient's VSK is 2.5-3.0 times higher than the control values.

With continuous intravenous infusion of sodium heparin, it is recommended to determine the initial APTT, then determine the APTT every 4 hours, then increase or decrease the rate of infusion of sodium heparin until the target APTT level is reached (1.5-2.5 times higher than the norm), further define APTT every b hours.

When bolus intravenous administration of heparin sodium, it is recommended to determine the initial APTT, then determine the APTT before each bolus injection with a subsequent increase or decrease of the administered dose of sodium heparin.

With subcutaneous administration of heparin sodium, APHT control is recommended 4-6 hours after injection, followed by an increase or decrease in the dose of heparin sodium administered.

With subcutaneous administration of small doses of sodium heparin (5000 ME 2-3 times a day) for the prevention of thrombus formation, it is not necessary to regularly monitor the APTT, it increases slightly.

Continuous intravenous infusion is the most effective way of using sodium heparin, better than regular (periodic) injections, because provides more stable hypocoagulation and less often causes bleeding.

The use of heparin sodium in special clinical situations.

Primary percutaneous coronary angioplasty in acute coronary syndrome without segment elevation ST and with myocardial infarction with segment elevation ST: heparin sodium is administered intravenously bolus in a dose of 70-100 IU / kg (unless the use of inhibitors of glycoprotein IIb/IIIa receptors) or in a dose of 50-60 IU / kg (when combined with inhibitors of glycoprotein IIb/IIIa receptors). Thrombolytic therapy for myocardial infarction with segment elevation ST: heparin sodium is administered intravenously bolus in a dose of 60 IU / kg (maximum dose of 4000 ME), followed by intravenous infusion at a dose of 12 IU / kg (not more than 1000 IU / hour) 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: heparin sodium is injected subcutaneously, deep into the fold of the abdominal skin.Initial dose of 5000 ME 2 hours prior to the beginning of the operation. In the postoperative period: 5000 ME 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 using extracorporeal circulation systems: the initial dose of heparin sodium 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 to 30,000 ME per 1 liter of 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 sodium heparin: 25-30 IU / kg (or 10,000 ME) intravenously bolus, then a continuous infusion of 20,000 IU of sodium heparin / 100 ml of a 0.9% solution of sodium chloride at a rate of 1500-2000 IU / h (unless otherwise specified in the guidelines for the use of hemodialysis systems).

Transition to warfarin therapy: To ensure a stable anticoagulant effect, heparin sodium should be continued in full dose until a stable target level of INR (international normalized ratio) is reached. After this, the administration should be stopped.

Transition to dabigatran therapy: Continuous intravenous administration of heparin sodium 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.

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 IU / kg intravenously bolus for 10 minutes.

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

The duration of therapy depends on the indications and the way of application.For intravenous use, the optimal treatment duration is 7-10 days then continue therapy with oral anticoagulants (oral anticoagulants recommended to appoint, starting from 1 day of treatment with sodium heparin or 5 to day 7, while use of sodium heparin stop for 4-5 days of combination therapy). With extensive thrombosis of the ileum-femoral veins, it is advisable to conduct longer-term courses of treatment with sodium heparin.

Elderly patients

Persons older than 60 years of age (especially in women) increased the risk of bleeding, in connection with which the dose of heparin sodium in these patients should be reduced.

Side effects:

The frequency of adverse events: frequent (1-10%), rare (0.1-1%), rare (0.01-0.1%), very rarely (less than 0.01%), the frequency is unknown (not be assessed on the basis of available data).

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 may develop bleeding in other organs, in Vol. H.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: Rare - skin redness, rash, itching and burning sensation in the soles, limb pain, pyrexia, rash, rhinitis, conjunctivitis, dyspnea, bronchospasm, angioedema: very rarely - anaphylactic shock.

Reactions at the site of administration: Often - irritation, soreness, redness of the tissues, slight bruising and ulceration at the injection site, rarely - gistaminonodobnye reactions (including skin necrosis at the injection site), very rarely - soft tissue calcification at the site of injection (predominantly in patients with severe chronic renal failure) .

Heparin-induced thrombocytopenia (HIT): severe immune reaction, It is caused by the formation of antibodies and leads 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 (incl.thrombosis of the deep veins of the legs, thromboembolism of the pulmonary artery, thrombosis of the cerebral veins, stroke, myocardial infarction, thrombosis of the mesenteric and renal arteries, thrombosis of the arteries of the extremities with development gangrene). Laboratory diagnosis: should determine 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).

At the beginning of treatment with sodium heparin, sometimes passing thrombocytopenia with a platelet count in the range from 80x10⁹/ l up to 150х10⁹/ l. Usually this situation does not lead to the development of complications, and treatment with heparin sodium can be continued. In rare cases, severe thrombocytopenia (white clot syndrome) can occur, sometimes fatal. This complication should be assumed in case of a decrease in platelets below 80x10⁹/ l or more than 50% of the original level, in such cases it is necessary to immediately cancel heparin sodium. If necessary, an alternative antithrombotic therapy should be prescribed. Patients with severe thrombocytopenia may develop coagulopathy of consumption (depletion of fibrinogen stores).

Against the background of heparin-induced thrombocytopenia: skin necrosis, arterial thrombosis, accompanied by the development of gangrene, myocardial infarction, stroke.

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 and low molecular weight heparins. If the patient needs antithrombotic therapy, other drugs should be used.

With prolonged use: osteoporosis, spontaneous fractures of bones, calcification of soft tissues, hypoaldosteronism, transient alopecia, priapism.

Against the background of heparin sodium therapy, changes in the biochemical parameters of blood can be observed (an increase in the activity of hepatic transaminases, free fatty acids and thyroxine in the blood plasma, hyperkalemia, recurrent hyperlipidemia with a reversal of heparin sodium, a false increase in the glucose concentration in the blood, and a false positive result of bromsulfalein test).

Other undesirable phenomena:

From the central nervous system and sense organs: infrequently - dizziness, headache.

From the cardiovascular system: infrequently - lowering blood pressure.

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

On the part of the organs of hematopoiesis: often - moderate thrombocytopenia (content platelets (150-100) x107L), 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 side of 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 - reversible in "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.

Overdose:

Symptoms: signs of bleeding.

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

With extensive bleeding, excess sodium heparin is neutralized with protamine sulfate (1 mg protamine sulphate per 100 mg ME heparin sodium). 1% (10 mg / ml) solution of protamine sulfate is administered intravenously very slowly. Every 10 minutes, you can not administer more than 50 mg (5 ml) of protamine sulfate. Given the rapid metabolism of heparin sodium, the required dose of protamine sulfate decreases with time. To calculate the required dose of protamine sulfate, it can be considered that T1 / 2 of sodium heparin is 30 minutes. In applying protamine sulfate severe anaphylactic reactions observed fatalities, in connection with which the drug should be administered only in offices equipped to provide emergency medical care in anaphylactic shock.

Hemodialysis is ineffective.

Interaction:

Due to the potentially possible precipitation of the active ingredients heparin sodium should not be mixed with other drugs.

Pharmaceutical interaction: The solution of heparin sodium is compatible with 0.9% sodium chloride solution.

A solution of sodium heparin is incompatible with the following drug solutions: alteplase, amikacin, amiodarone, ampicillin sodium, benzylpenicillin sodium, ciprofloxacin, cytarabine, dacarbazine, danorubicin, diazepam, dobutamine, doxorubicin hydrochloride, droperidol, erythromycin, gentamycin sulfate, haloperidol lactate, hyaluronidase, hydrocortisone sodium succinate, dextrose (glucose), idarubicin, kanamycin sulfate, sodium methicillin, netilmicin sulfate, opioids, oxytetracycline hydrochloride, POLYMIX on B sulfate, promazine hydrochloride, promethazine hydrochloride, streptomycin sulfate, diethanolamine sulfafurazola, tetracycline hydrochloride, tobramycin sulfate, cephalothin sodium, cephaloridine, vancomycin hydrochloride, vinblastine sulfate, labetalol hydrochloride, nicardipine hydrochloride.

Pharmacokinetic interaction: heparin sodium expels 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), glucocorticosteroids and dextran, 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.

Before any surgical interventions using heparin, oral anticoagulants and antiplatelet agents should be discontinued for at least 5 days,they can increase bleeding during surgery or in the postoperative period. Sodium heparin anticoagulant activity decreases while the use of ACTH, antihistamines, ascorbic acid, ergot alkaloids, nicotine, nitroglycerin, cardiac glycosides, thyroxine, tetracycline and quinine.

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

Special instructions:

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).

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

In people over 60 years (especially women), the risk of bleeding is increased, due to which the dose of sodium heparin 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.

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.

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

Data on the effect of the drug on the ability to manage transport and other mechanisms are not available.

Form release / dosage:

A solution for intravenous and subcutaneous administration of 5000 IU / ml.

Packaging:

1 ml or 5 ml in ampoules of colorless neutral glass type I with a color fracture ring or with a colored dot and a notch. One, two or three color rings and / or a two-dimensional bar code, and / or alphanumeric coding or without additional color rings, a two-dimensional bar code, alphanumeric coding are applied to the ampoules.

By 5 ampoules in a contour cell box made of a polyvinylchloride film and aluminum foil or a polymer film, or without a foil and film.

1 or 2 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004561

Date of registration:27.11.2017

Expiration Date:27.11.2022

The owner of the registration certificate:FarmSirma Soteks, ZAO FarmSirma Soteks, ZAO Russia

Manufacturer: & nbsp

FarmSirma Soteks, ZAO Russia

Information update date: & nbsp10.01.2018

Illustrated instructions

Instructions

Sodium Heparin (Heparin sodium)