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

gasoline alcohol - 9.0 mg, sodium chloride - 3.4 mg, 1 M hydrochloric acid solution or 1M sodium hydroxide solution to pH 5.0 - 7.5, water for injection - up to 1 ml.

Description:Transparent colorless or light yellow liquid.

Pharmacotherapeutic group:Anticoagulant 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 application.

The mechanism of action of heparin is based primarily on its binding to antithrombin III, an inhibitor of activated coagulation factors: thrombin, IXa, Xa, XIa,XIIa (especially important is 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 interaction with enzymes, it can increase the activity of brain tyrosine hydroxylase, pepsinogen, DNA polymerase and reduce the activity of myosin ATPase, pyruvic kinase, RNA polymerase, pepsin.

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

In high doses it is effective for pulmonary embolism and venous thrombosis, in small doses for prophylaxis of venous thromboembolism, incl. 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; duration of anticoagulant effect accordingly - 4-5, 6, 8 hours and 1-2 weeks, therapeutic effect - prevention of thrombus formation - persists significantly 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 breast milk. Intensively captured by endothelial cells and cells of the mononuclear-macrophage system (cells of the REE (reticuloendothelial system), concentrated in the liver and spleen, metabolized in the liver with the participation of N-desulfamidase and heparinase of platelets, which is involved in the metabolism of heparin at later stages.Participation in the metabolism of platelet factor IV (anti-heparin factor), as well as binding of heparin to the macrophage system, explain rapid biological inactivation and short-term action.Desulfated molecules under the influence of kidney endoglycosidase are converted into low-molecular fragments. T1 / 2 - 1-6 hours (an average of 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:

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

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), erosive-ulcerative lesions, tumors and polyps of the gastrointestinal tract (gastrointestinal tract); subacute bacterial endocarditis; marked violations of the liver and kidneys; cirrhosis of the liver, accompanied by varicose veins of the esophagus, severe uncontrolled arterial hypertension; hemorrhagic stroke; recent operations on the brain and spinal column, eyes, prostate gland, liver, or bile duct; states after spinal cord puncture, proliferative diabetic retinopathy; diseases accompanied by a decrease in clotting time; menstrual period, threatening miscarriage, childbirth (including recent ones), pregnancy, lactation period; thrombocytopenia; increased vascular permeability; pulmonary hemorrhage.

Carefully:

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

Dosing and Administration:

Heparin is administered in the form of continuous intravenous infusion or in the form of subcutaneous or intravenous injections.

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

Supporting doses are determined depending on the method of application:

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

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

- when administered subcutaneously, every 12 hours, 15,000-20,000 IU or every 8 hours at 8,000-10,000 IU.

Before the administration of each dose, it is necessary to conduct a study of blood coagulation time and / or activated partial thromboplastin time (APTT) in order to correct the subsequent dose. Subcutaneous injections are preferably performed in the anterior abdominal wall area, other places of administration (shoulder, thigh) can be used as an exception. An anticoagulant effect of heparin is considered optimal if the clotting time is 2-3 times longer than normal, activated partial thromboplastin time (APTT) and

thrombin time is increased by 2 times (with the possibility of continuous monitoring of APTT).

Patients who are on the extracorporeal circulation, heparin is prescribed in a dose of 150-400 IU / kg body weight or 1500-2000 IU / 500 ml of canned blood (whole blood, erythrocyte mass).

Patients on dialysis, dose adjustment is conducted according to the results of the coagulogram.

For children, the drug is administered intravenously 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 APTT (activated partial thromboplastin time ).

Side effects:

Allergic reactions: hyperemia of the skin, drug fever, hives, rhinitis, pruritus and sensation 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) can sometimes be noted with a platelet count ranging from 80x10⁹/ l up to 150x10⁹/ l. Usually this situation does not lead to the development of complications and the treatment with heparin 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 the number of platelets below 80x10⁹/ l or more than 50% of the baseline, the administration of heparin in such cases is urgently discontinued. Patients with severe thrombocytopenia may develop coagulopathy of consumption (depletion of fibrinogen stores).

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

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

On the background of heparin therapy can be observed changes in biochemical blood parameters (increase in activity "liver" enzymes, free fatty acids and thyroxine in the blood plasma; reversible potassium retention in the body; false lowering cholesterol; false increase in blood glucose level and the error in the results bromsulfaleinovogo test) . Local reactions: irritation, pain, hyperemia, hematoma and ulceration at the injection site, bleeding.

Bleeding: typical - from the digestive tract (gastrointestinal tract) and the urinary tract, at the site of injection, 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 (adenocorticotropic hormone), alkaline amino acids and polypeptides, protamine may reduce the effect of heparin. Dextran, phenylbutazone, indomethacin, sulfeenpyrazone, 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, tk. they can bind to heparin.

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

Special instructions:

Treatment in large doses is recommended in a hospital. The control of the number of platelets should be performed before the start of treatment, on the first day of treatment and at short intervals during the entire period of administration of heparin,especially between 6 and 14 days after initiation of treatment. Immediately stop treatment with a sharp decrease in the number of platelets (see "Side Effects").

A sharp decrease in the number of platelets requires further investigation for the detection of heparin-induced immune thrombocytopenia. If this is the case, the patient should be informed that he can not prescribe heparin in the future (even low molecular weight heparin). If there is a high probability of heparin-induced immune thrombocytopenia, heparin should be immediately withdrawn.

When developing heparin-induced thrombocytopenia 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 clot syndrome) should not undergo hemodialysis with heparinization. If necessary, alternative methods of treating renal failure should be used.

To avoid overdose, it is necessary to constantly monitor clinical symptoms indicating possible bleeding (bleeding of the mucous membranes, hematuria, etc.).In individuals with a lack of response to heparin or requiring the appointment of high doses of heparin, it is necessary to monitor the level of antithrombin III.

Although heparin does not penetrate the placental barrier and is not detected in breast milk, it should be carefully monitored in pregnant doses by pregnant women and breast-feeding mothers.

Special care should be taken within 36 hours after delivery. It is necessary to conduct appropriate control laboratory tests (clotting time, activated partial thromboplastin time and thrombin time).

In women over 60 years of age, heparin can increase bleeding.

When using heparin in patients with hypertension should constantly monitor blood pressure.

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

Patients who are switched to oral anticoagulant therapy, the appointment of heparin should be continued until the results of clotting time and activated partial thromboplastin time (APTT) will not be in the therapeuticrange.

Intramuscular injections should be excluded when administering heparin for therapeutic purposes. Puncture biopsies, infiltration and epidural anesthesia and diagnostic lumbar punctures should also be avoided whenever possible.

If massive bleeding occurs, you should abolish heparin and examine the coagulogram indices. If the results of the analysis are within the limits of the norm, then the probability of development of this bleeding due to the use of heparin is minimal; Changes in the coagulogram tend to normalize after heparin withdrawal.

Protamine sulfate is a specific antidote for heparin. One ml of protamine sulfate neutralizes 1000 IU of heparin. Doses of protamine should be corrected depending on the results of the coagulogram, since an excessive amount of this drug itself can provoke bleeding.

Form release / dosage:

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

Packaging:

In ampoules of 5 ml or in bottles of 5 ml. 5 ampoules per contour cell pack.

1 circuit cell pack with instruction on the use of the drug, a knife or a scapegrator ampullum in a pack of cardboard.

For 30 or 50 contiguous cell packs with a foil with 30 or 50 instructions for the use of the drug, respectively, knives or scarifiers ampoule in boxes of cardboard or boxes of corrugated cardboard (for inpatient).

When packing ampoules with notches, rings or break points, knives or scarifier ampoules do not.

5 bottles per circuit pack.

1 circuit cell pack with instructions for the use of the drug in a pack of cardboard.

For 30 or 50 contoured cell packs with foil with 30 or 50 instructions for the use of the drug, respectively, in boxes of cardboard or in boxes of corrugated cardboard (for inpatient).

Storage conditions:

In the dark place at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

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

Terms of leave from pharmacies:On prescription

Registration number:P N002077 / 01

Date of registration:21.11.2008 / 25.05.2015

Expiration Date:Unlimited

The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Information update date: & nbsp24.03.2017

Illustrated instructions

Instructions

Heparin (Heparin)