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

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 heparin is primarily based on (binding to antithrombin III, a physiological inhibitor of activated blood coagulation factors IXa, Xa, XIa, XIIa and thrombin, especially the ability to inhibit activated factor X,involved in the internal and external coagulation system (this action is manifested against the background of much smaller doses of heparin than is required to suppress the activity of thrombin, promoting the formation of fibrin from fibrinogen, which serves as a rationale for the possibility of subcutaneous administration of small doses of heparin for the prevention of venous thrombosis and high doses of Heparin has the ability to suppress platelet aggregation (prolongs the time of bleeding) .Heparin is unable to dissolve thrombus (not fibrinolytic), but can reduce the size thrombus, stopping its increase, and in this case part of the thrombus dissolves under the action of natural fibrinolytic enzymes.Inhibits the activity of hyaluronidase, has a hypolipidemic effect.The anticoagulant action with a single IV injection develops in a few minutes and lasts up to 4-5 hours. to the introduction of the action begins in 20-30 minutes and lasts 12 hours or more (depending on the dose) .For unfractionated standard heparin, the ratio of activity (antifactor Xa) and anticoaculant activity (APTTV) is 1: 1.

Pharmacokinetics:After subcutaneous administration, the maximum concentration in the plasma is determined after 4-5 hours. With blood plasma proteins, up to 95% of heparin binds, the distribution volume is very small - 0.06 l / kg (does not leave the vascular bed due to strong association with blood plasma proteins). It does not penetrate the placenta and into breast milk. Metabolised in the liver with heparinase. Participation in the metabolism of platelet factor IV, as well as the binding of heparin to the macrophage system, explains the rapid biological inactivation and short-term action. It is excreted in urine, mainly in the form of inactive metabolites. T1 / 2 ranges from 23 minutes. up to 5 hours.

Indications:Prophylaxis and therapy: deep vein thrombosis, pulmonary embolism (including peripheral veins), coronary thrombosis; unstable angina; acute myocardial infarction; Atrial fibrillation accompanied by embolization; DIC-syndrome (the first phase).
Prevention of blood coagulation during operations using extracorporeal blood circulation methods, blood transfusion, hemodialysis, blood sampling for research.

Contraindications:Hypersensitivity to heparin, diseases showing increased bleeding (hemophilia, thrombocytopenia, etc.), bleeding, aneurysm of the cerebral vessels, exfoliating aortic aneurysm, hemorrhagic stroke, antiphospholipid syndrome, trauma (especially craniocerebral), severe arterial hypertension, erosive-ulcerative lesions of the organs of the gastrointestinal tract; cirrhosis of the liver accompanied by varicose veins of the esophagus, renal failure, bacterial endocarditis, menstruation, pregnancy, threatening miscarriage, childbirth (including recent ones), lactation period, recent surgical interventions on the eyes, brain, prostate, liver and biliary pathways, condition after spinal cord puncture.

Carefully:Persons suffering from polyvalent allergy (heparin is an extract from animal tissue), arterial hypertension, hepatic insufficiency, dental manipulation, diabetes mellitus, pericarditis, IUD, active tuberculosis, radiation therapy, elderly (over 60 years, especially women).

Dosing and Administration:With a therapeutic purpose, heparin is prescribed in the form of continuous intravenous infusion or in the form of regular IV injections. With a prophylactic goal - SC, at 5,000 IU / day, at intervals of 8-12 hours. The usual place for subcutaneous injections is the anterolateral wall (in exceptional cases, injected into the upper region of the shoulder or thigh), while using a thin long needle , which should be inserted perpendicularly, into the pinched skin fold held between the thumb and forefinger until the end of the solution. Heparin with subcutaneous injection should be injected deep into the adipose tissue, alternating the injection site (in order to avoid the formation of a hematoma). The first injection should be performed 1-2 hours before the operation; in the postoperative period - enter within 7-10 days, and if necessary - for a longer time.
The initial dose of heparin administered for therapeutic purposes is usually 5000 IU and is administered iv, after which the treatment is continued using podkazhnye injections or IV infusion.
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 in 1000 ml of isotonic sodium chloride solution;
- with regular IV injections, 5000-10000 IU of heparin is administered every 4 to 6 hours;
- when administered subcutaneously, every 12 hours, 15,000 to 20,000 ME or every 8 hours to 8000-10000 ME.
Doses of heparin are selected so that the activated partial thromboplastin time (APTT) was 1.5-2.5 times greater than the congrolic one. When subcutaneous administration of small doses: 5000 ME 2 times a day (prevention of thrombosis), regular monitoring of APTT is not required, since it does not increase significantly. Continuous intravenous infusion is the most effective way of using heparin, which is better than regular injections, as it provides more stable hypocoagulation and less often causes bleeding. Intravenous injection is recommended to be administered only with the use of initial doses or if for any reason it is impossible to use an intravenous infusion or a subcutaneous injection. Repeated IV injections cause significant fluctuations in hemostasis and rush cause dangerous bleeding, so they are prescribed only when absolutely necessary.
Adults with thromboses of mild to moderate severity are given IV, 40,000-50000 IU / day for 3-4 injections; with severe thrombosis and embolism - in / in 20,000 IU 4 times a day with an interval of 6 hours.
For vital indications, I / O is administered once 25000 ME, then 20000 IU every 4 hours until a daily dose of 80000-120000 ME is reached.When I / in the drip introduction to the daily volume of the infusion solution add at least 40,000 IU.
When carrying out the extracorporeal circulation, administer a dose of 140-400 IU / kg or 1500-2000 IU per 500 ml of blood. When hemodialysis is first introduced in / in 10000 ME, then in the middle of the procedure - another 30,000-50000 ME. For the elderly, especially women, the dose should be reduced.
For children, the drug is injected intravenously: 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; The dose should be selected so that the clotting time is 20 minutes.
The duration of therapy with heparin depends on the indications and the way of application. With the / in application, the optimal duration of treatment is 7-10 days, after which the therapy is continued with oral anticoagulants (it is recommended to appoint oral anticoagulants starting from 1 day of treatment with heparin or from 5 to 7 days, and stopping the use of heparin on the 4th-5th day of combined therapy ). In cases of extensive thrombosis of the iliac-femoral veins, longer courses of heparin treatment are advisable.

Side effects:The tolerability of heparin is usually good. Perhaps the development of allergic reactions: skin hyperemia, drug fever, hives, rhinitis, asthma, pruritus and a feeling of heat in the soles, bronchospasm,collapse, anaphylactic shock. Dizziness, headaches, nausea, decreased appetite, vomiting, diarrhea. Thrombocytopenia (6% of patients) may result from the direct action of heparin or an immune response in which antibodies react with platelets and endothelium. Reactions of the first type, as a rule, appear in a mild form and disappear after discontinuation of therapy, and reactions of the second type have a severe course and can be fatal. Against the background of heparin-induced thrombocytopenia, skin necrosis and arterial thrombosis ("white blood clots") can occur, accompanied by gangrene, myocardial infarction, stroke. With the development of severe thrombocytopenia (a decrease in the number of platelets by 2 times from the initial number or below 100,000), it is necessary to stop the use of heparin. Against the background of long-term use of heparin, cases of osteoporosis, spontaneous bone fractures, hypoaldosteronism, transient alopecia and increased activity of "liver" transaminases (ALT and ACT) are described. Of the local side effects, irritation, pain, erythema, hematoma and ulceration at the site of administration are possible.Bleeding also refers to the characteristic complications of heparin therapy (the risk can be minimized by careful assessment of contraindications, regular laboratory control of blood coagulation and accurate dosage). Typical bleeding from the gastrointestinal tract and urinary tract, bleeding at the injection site, in areas undergoing pressure, from surgical wounds, as well as hemorrhage in other organs (adrenal, yellow body, retroperitoneal space) are typical.

Overdose:For small bleedings, 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 should be borne in mind that heparin is rapidly eliminated, and if protamine sulfate is prescribed 30 minutes after the previous dose of heparin, only half the required dose should be administered, the maximum dose protamine sulfate is 50 mg.

Interaction:The action of heparin is enhanced: antibiotics (reduce the formation of vitamin K by intestinal microflora), acetylsalicylic acid, dipyridamole, non-steroidal anti-inflammatory drugs and other agents that reduce platelet aggregation (remaining the main mechanism of hemostasis in patients beyond the background of heparin treatment), indirect anticoagulants; drugs that block tubular secretion.
The effect of heparin is reduced: antihistamines, phenothiazines, cardiac glycosides, a nicotinic acid, ethacrynic acid, tetracyclines, ergot alkaloids, nicotine, nitroglycerine (iv administration), thyroxine, ACTH, alkaline amines and polypeptides, protamine.
Do not mix in the same syringe 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 medicinal purposes, its dose is selected depending on the value of APTTV.
During the application of heparin, other drugs should not be given intramuscularly and organ biopsies should be performed.
To dilute heparin use only physiological solution.
It is possible to use pregnancy only on strict indications.
While heparin does not cross into breast milk, his appointment to nursing mothers in some cases caused a rapid (within 2-4 weeks) the development of osteoporosis and spinal cord injury.

Form release / dosage:A solution for intravenous and subcutaneous administration of 5000 IU / ml.

Packaging:For 1 ml, 5 ml in ampoules or in glass bottles, ukuporennyh rubber stoppers and rolled aluminum caps.
5 or 10 vials (vials) were placed in packs or cartons of cardboard with instructions for use, or knife ampulnam lancet. When packaging ampoules that have a ring or an opening point, the ampoule knife or scarifier does not insert.
For 5 or 10 ampoules (vials) are placed in a contour mesh package. For 1 or 2 contour packs with instructions for use, with a knife ampoule or scarifier (if necessary) in a pack of cardboard.

Storage conditions:List B. In a dry, protected from light and out of reach of children, at a temperature of 12 to 15 ° C.

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

Terms of leave from pharmacies:On prescription

Registration number:P N000185 / 01

Date of registration:17.03.2008

The owner of the registration certificate:MICROGEN FGUP Scientific and Production Association MICROGEN FGUP Scientific and Production Association Russia

Manufacturer: & nbsp

MICROGEN FGUP NGO Russia

Information update date: & nbsp2016-01-14

Illustrated instructions

Instructions

Heparin (Heparin)