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

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 application.

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 (especially the ability to inhibit thrombin and activated factor X).

Increases renal blood flow; increases the resistance of blood vessels of the brain, reduces the activity of brain hyaluronidase, activates lipoprotein lipase and has lipid-lowering effect.

Reduces the activity of the surfactant in the lungs, suppresses the 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 the interaction with enzymes, it can increase the activity of the tyrosine hydroxylase of the brain, pepsinogen, DNA polymerase and reduce the activity of myosin ATPase, pyruvate kinase, RNA polymerase, pepsin.

Heparin is not able to dissolve the thrombus (it is not fibrinolytic), but it can reduce the size of the thrombus, stopping its growth, and in this case part of the thrombus dissolves under the action of the fibrinolytic enzyme-plasmin. Oppressing the activity of hyaluronidase, has lipid-lowering effect.

In patients with ischemic heart disease (in combination with ASA (acetylsalicylic acid)) reduces the risk of developing acute coronary thrombosis, myocardial infarction and sudden death.Reduces the frequency of recurrent myocardial infarction and mortality of patients with myocardial infarction.

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

With intravenous administration, blood clotting slows down almost immediately, with intramuscular injection - after 15-30 minutes, with subcutaneous - after 20-60 minutes, after inhalation, the maximum effect - in a day; the duration of the anticoagulant effect is 4-5, 6, 8 hours and 1-2 weeks, respectively, and the therapeutic effect - prevention of thrombus formation - lasts much longer.

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

Pharmacokinetics:

After subcutaneous administration, TCmax 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 mononuclear-macrophage system (cells of RES (reticuloendothelial system)), 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 the 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:

Treatment and prevention: deep vein thrombosis, pulmonary embolism (including peripheral veins), coronary artery thrombosis, thrombophlebitis, unstable angina, acute myocardial infarction, atrial fibrillation (incl.accompanied by embolization), disseminated intravascular coagulation syndrome, prevention and therapy of microthrombosis and microcirculation disorders, renal vein thrombosis, hemolytic syndrome, mitral heart disease (thrombogenesis prophylaxis), bacterial endocarditis, glomerulonephritis, lupus nephritis.

Prevention of blood coagulation during operations using extracorporeal circulation methods, hemodialysis, hemosorption, peritoneal dialysis, cythereferis, forced diuresis, washing of venous catheters.

Contraindications:

Hypersensitivity to heparin, diseases accompanied by increased hemorrhage (hemophilia, thrombocytopenia, vasculitis, etc.), bleeding, aneurysm of cerebral vessels, exfoliating aortic aneurysm, hemorrhagic stroke, antiphospholipid syndrome, trauma (especially craniocerebral), uncontrolled arterial hypertension, erosive - ulcerative lesions of the gastrointestinal tract; cirrhosis of the liver, accompanied by varicose veins of the esophagus; menstrual period, threatening miscarriage, childbirth (including recent ones),recent surgical interventions on the eyes, brain, prostate, liver and biliary tract, condition after spinal cord puncture, pregnancy, lactation, children under 1 month.

Carefully:

Persons suffering from polyvalent allergy (including bronchial asthma), arterial hypertension, dental manipulation, diabetes mellitus, endocarditis, pericarditis, intrauterine contraceptives (IUD), active tuberculosis, radiation therapy, hepatic insufficiency, chronic renal failure (CRF), advanced age (over 60 years, especially women).

Dosing and Administration:

Heparin is administered subcutaneously, intravenously, bolus or drip. Heparin can not be administered intramuscularly. 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).

For prophylactic purposes, subcutaneously, 5,000 IU / day, at intervals of 8-12 hours. The usual place for subcutaneous injections is the anterolateral wall of the abdomen (in exceptional cases, it is inserted into the upper region of the shoulder or thigh), using a thin The needle, which should be injected deeply,perpendicular to 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, administer within 7-10 days, and if necessary - for a longer time.

The initial dose of heparin administered for therapeutic purposes is usually 5,000 IU and is administered intravenously, after which the treatment is continued using intravenous infusions.

Supporting doses are determined depending on the method of application:

- with continuous intravenous infusion, appoint 1-2 thousand IU / h (24-48 thousand IU / day), diluting heparin in a 0.9% solution of sodium chloride;

- with periodic intravenous injections appoint 5-10 thousand IU of heparin every 4 hours.

Doses of heparin for intravenous administration are selected so that the activated partial thromboplastin time (APTT) was 1.5-2.5 times greater than the control one. When subcutaneous administration of small doses (5 thousand ME 2-3 times a day) for the prevention of thrombosis, regular monitoring of APTTV is not required, it increases slightly.

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

When carrying out the extracorporeal circulation, administer a dose of 140-400 IU / kg or 1.5-2 thousand IU per 500 ml of blood. When hemodialysis, first enter / in 10 thousand ME, then in the middle of the procedure - another 30-50 thousand ME. For the elderly, especially women, the dose should be reduced.

For children, the drug is given IV drip: at the age of 1-3 months - 800 IU / kg / day, 4-12 months -700 IU / kg / day, over 6 years - 500 IU / kg / day under the control of APTTV.

Side effects:

Allergic reactions: hyperemia of the skin, drug fever, urticaria, rhinitis, pruritus and heat sensation in the soles, bronchospasm, collapse, anaphylactic shock, dizziness, headaches, nausea, decreased appetite, vomiting, diarrhea. Thrombocytopenia (6% of patients), in rare cases with fatal outcome.

Against the background of heparin-induced thrombocytopenia: skin necrosis, arterial thrombosis, accompanied by the development of gangrene, myocardial infarction, stroke. With the development of severe thrombocytopenia (2 times the initial number or less than 100 thousand / mm3), heparin is rapidly stopped.

With prolonged use: osteoporosis, spontaneous bone fractures, calcification of soft tissues, hypoaldosteronism, transient alopecia, increased activity of "liver" transaminases.

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

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

Overdose:

Symptoms: signs of bleeding. Treatment: with small 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 sulphate per 100 IU of heparin). It must be borne in mind that heparin is rapidly excreted, and if Protamine sulfate appointed 30 minutes after the previous dose of heparin, only half the required dose should be administered; The maximum dose of protamine sulfate is 50 mg. Hemodialysis is ineffective.

Interaction:

Before any surgical interventions, with the use of heparin, oral anticoagulants (for example, dicoumarins) and antiplatelet agents (for example, acetylsalicylic acid, dipyridamole), 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 (adrenocorticotropic hormone), alkaline amino acids and polypeptides, protamine may reduce the action 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 in the places of their binding with proteins. Mutual reduction in efficacy occurs with the simultaneous use of tricyclic antidepressants, since they can bind to heparin.

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

Special instructions:

Heparin can not be administered intramuscularly, since it is possible to form a hematoma at the injection site.

A solution of heparin can acquire a yellow tint, which does not change its activity or tolerability.

When prescribing heparin for therapeutic purposes, its dose is selected depending on the value of APTT (activated partial thromboplastin time).

During the application of heparin, other drugs should not be administered intramuscularly, organ biopsies should be performed.

To dilute heparin use only 0.9% sodium chloride solution.

Although heparin does not penetrate into breast milk, the administration of it to nursing mothers in some cases caused a rapid (within 2-4 weeks) development of osteoporosis and spinal injury.

Form release / dosage:

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

Packaging:5 or 10 ml in bottles. For 1 or 5 bottles together with the 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.

Keep out of the reach of children.

Shelf life:4 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N015248 / 01

Date of registration:22.07.2009 / 12.01.2016

Expiration Date:Unlimited

The owner of the registration certificate:BELMEDPREPARATY, RUP BELMEDPREPARATY, RUP Republic of Belarus

Manufacturer: & nbsp

BELMEDPREPARATY, RUP Republic of Belarus

Information update date: & nbsp24.03.2017

Illustrated instructions

Instructions

Heparin (Heparin)