Compound
The injection solution contains sodium heparin at a concentration of 5 thousand units/ml.
The auxiliary components of the drug include sodium chloride, benzyl alcohol, and water. 1 gram of gel contains 1 thousand units of sodium heparin , as well as auxiliary components: 96% ethanol, carbomer , dimethyl sulfoxide, propylene glycol, dietanolamine, methyl and propylparaben (additives E 218, E 216), lavender oil and purified water.
pharmachologic effect
Pharmacological group: anticoagulants .
Group of the drug Heparin, produced in the form of a gel: drugs for the treatment of cardiovascular diseases.
Group of the drug Heparin, produced in injection form: agents affecting blood and hematopoiesis.
Heparin sodium contained in the drug has an antithrombotic effect , slows down the aggregation and adhesion of leukocytes , platelets and erythrocytes ; reduces wall spasm and the degree of vascular permeability; helps improve collateral circulation.
Pharmacodynamics and pharmacokinetics
What is Heparin?
Heparin (INN: Heparin) is an acidic mucopolysaccharide with Mr about 16 kDa. A direct anticoagulant that helps slow down the formation of fibrin .
The gross formula of heparin is C12H19NO20S3.
Pharmacodynamics
The mechanism of action of heparin is based primarily on its binding to AT III (its plasma cofactor). Being a physiological anticoagulant , it potentiates the ability of AT III to suppress activated coagulation factors (in particular, IXa, Xa, XIa, XIIa).
When used in high concentrations, heparin also inhibits thrombin activity .
Suppresses activated factor X, which is involved in the internal and external blood coagulation system.
The effect occurs when significantly lower doses of heparin are used than are required to inhibit the activity of coagulation factor II ( thrombin ), which promotes the formation of fibrin from the plasma protein fibrinogen .
This justifies the possibility of using small doses of heparin (subcutaneously) for prophylactic purposes, and large doses for treatment.
Heparin is not a fibrinolytic (i.e., it is capable of dissolving blood clots), but it can reduce the size of the blood clot and stop its expansion. Thus, the blood clot is partially dissolved under the action of fibrinolytic enzymes of natural origin.
Suppresses the activity of the enzyme hyaluronidase, helps reduce the activity of surfactant in the lungs.
Reduces the risk of developing MI, acute thrombosis of myocardial arteries and sudden death. In small doses it is effective for the prevention of VTE, in high doses it is effective against venous thrombosis and pulmonary embolism .
Deficiency of AT III at the site of thrombosis or plasma may reduce the antithrombotic effect of the drug
When applied externally, the product has a local antiexudative , antithrombotic and moderate anti-inflammatory effect .
Promotes the activation of fibrinolytic properties of blood, inhibits the activity of hyaluronidase, and blocks the formation of thrombin. Gradually released from the gel and passing through the skin, heparin helps reduce inflammation and has an antithrombotic effect .
At the same time, the patient’s microcirculation improves and tissue metabolism is activated and, as a result, the processes of resorption of blood clots and hematomas are accelerated, and tissue swelling is reduced.
Pharmacokinetics
When used externally, absorption is negligible.
After injection under the skin, TCmax is 4-5 hours. Up to 95% of the substance is in a state bound to plasma proteins, Vp - 0.06 l/kg (the substance does not leave the vascular bed due to strong binding to plasma proteins).
It does not penetrate the placental barrier or into breast milk.
Metabolized in the liver. The substance is characterized by rapid biological inactivation and short duration of action, which is explained by the participation of the antiheparin factor in its biotransformation and the binding of heparin to the macrophage system.
T1/2 - 30-60 minutes. Excreted by the kidneys. Up to 50% of the substance can be excreted unchanged only if high doses are used. It is not excreted by hemodialysis.
Heparin sodium, 5000 IU/ml, solution for intravenous and subcutaneous administration, 5 ml, 5 pcs.
Treatment with large doses is recommended in a hospital setting.
Platelet counts should be monitored before starting treatment, on the first day of treatment and at short intervals throughout the period of heparin administration, especially between 6 and 14 days after the start of treatment. Treatment should be stopped immediately if there is a sharp decrease in the platelet count.
A sharp decrease in platelet count requires further investigation to identify heparin-induced immune thrombocytopenia.
If this occurs, 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 likelihood 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 event of thromboembolic complications, other antithrombotic agents should be used.
Patients with heparin-induced immune thrombocytopenia (white thrombus syndrome) should not undergo heparinized hemodialysis. If necessary, they should use alternative methods of treatment for renal failure.
To avoid overdose, it is necessary to constantly monitor clinical symptoms indicating possible bleeding (bleeding of the mucous membranes, hematuria, etc.). In individuals who do not respond to heparin or require high doses of heparin, antithrombin III levels should be monitored.
Although heparin does not cross the placental barrier and is not detected in breast milk, pregnant women and breastfeeding mothers should be carefully monitored when administered at therapeutic doses.
Particular care should be taken for 36 hours after birth. It is necessary to carry out appropriate control laboratory tests (blood clotting time, activated partial thromboplastin time and thrombin time).
In women over 60 years of age, heparin may increase bleeding.
When using heparin in patients with arterial hypertension, blood pressure should be constantly monitored.
A coagulation profile should always be performed before initiating heparin therapy, unless low doses are used.
In patients who are switched to oral anticoagulant therapy, heparin should be continued until clotting time and activated partial thromboplastin time (aPTT) results are within the therapeutic range.
Intramuscular injections should be excluded when prescribing heparin for therapeutic purposes. Needle biopsies, infiltration and epidural anesthesia, and diagnostic lumbar punctures should also be avoided whenever possible.
If massive bleeding occurs, heparin should be discontinued and coagulation parameters should be examined. If the test results are within normal limits, then the likelihood of developing this bleeding due to the use of heparin is minimal; Changes in the coagulogram tend to normalize after discontinuation of heparin.
Protamine sulfate is a specific antidote for heparin. One ml of protamine sulfate neutralizes 1000 IU of heparin. Doses of protamine should be adjusted depending on the results of the coagulogram, since an excessive amount of this drug itself can provoke bleeding.
Indications for use
Indications for use of the gel
Heparin gel is used for the treatment and prevention of thrombophlebitis of the superficial veins , phlebitis (post-injection and post-infusion), lymphangitis , superficial periphlebitis, elephantiasis, localized infiltrates, bruises, swelling and injuries (including muscles, joints, tendons), superficial mastitis , subcutaneous hematomas .
Indications for use of the solution
Heparin injections are prescribed for thrombosis of deep veins , myocardial arteries , renal veins , pulmonary embolism, thrombophlebitis , atrial fibrillation (including if cardiac arrhythmia is accompanied by embolization), unstable angina , disseminated intravascular coagulation syndrome , acute myocardial infarction, mitral heart disease (prevention of blood clots ), bacterial endocarditis , hemolyticouremic syndrome , lupus nephritis , glomerulonephritis , for the prevention and treatment of microthrombosis and microcirculation disorders.
For preventive purposes, the drug is used during surgical interventions that use extracorporeal blood circulation methods, during cytapheresis, peritoneal dialysis, hemodialysis, forced diuresis, hemosorption, and when washing venous catheters.
When Heparin is administered intravenously, blood clotting slows down almost immediately, when administered into a muscle - after 15-30 minutes, when administered subcutaneously - after 20-60 minutes, when administered by inhalation, the effect is most pronounced after 24 hours.
Heparin sodium salt
Direct anticoagulant, belongs to the group of medium molecular heparins. In blood plasma, it activates antithrombin III, accelerating its anticoagulant effect. It disrupts the transition of prothrombin to thrombin, inhibits the activity of thrombin and activated factor X, and to some extent reduces platelet aggregation.
For unfractionated standard heparin, the ratio of antiplatelet activity (antifactor Xa) to anticoagulant activity (APTT) is 1:1.
Increases renal blood flow; increases cerebral vascular resistance, reduces the activity of cerebral hyaluronidase, activates lipoprotein lipase and has a hypolipidemic effect. Reduces the activity of 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, it can increase the activity of brain tyrosine hydroxylase, pepsinogen, DNA polymerase and reduce the activity of myosin ATPase, pyruvate kinase, RNA polymerase, pepsin.
There is evidence that heparin has immunosuppressive activity.
In patients with coronary artery disease (in combination with ASA), it reduces the risk of acute coronary artery thrombosis, myocardial infarction and sudden death. Reduces the frequency of recurrent infarctions and mortality in patients who have had myocardial infarction. In high doses it is effective for pulmonary embolism and venous thrombosis, in small doses it is effective for the prevention of venous thromboembolism, incl. after surgical operations.
With intravenous administration, blood coagulation slows down almost immediately, with intramuscular injection - after 15-30 minutes, with subcutaneous administration - after 20-60 minutes, after inhalation the maximum effect is within 24 hours; the duration of the anticoagulant effect is respectively 4-5, 6, 8 hours and 1-2 weeks, the therapeutic effect - prevention of thrombus formation - lasts much longer. Deficiency of antithrombin III in plasma or at the site of thrombosis may reduce the antithrombotic effect of heparin.
When applied externally, it has a local antithrombotic, antiexudative, and moderate anti-inflammatory effect. Blocks the formation of thrombin, inhibits the activity of hyaluronidase, and activates the fibrinolytic properties of the blood. Heparin penetrating through the skin reduces the inflammatory process and has an antithrombotic effect, improves microcirculation and activates tissue metabolism, thereby accelerating the processes of resorption of hematomas and blood clots and reducing tissue swelling.
Contraindications
Heparin containing ointments (Heparin, Heparin-Acrigel 1000, etc.) are contraindicated in cases of hypersensitivity to the components they contain, as well as in diseases accompanied by ulcerative-necrotic processes, and injuries that are accompanied by violations of the integrity of the skin.
Heparin gel (ointment) should be used with caution in case of thrombocytopenia and increased tendency to bleeding.
Contraindications to the use of the injection form of the drug:
- hypersensitivity;
- diseases accompanied by increased bleeding ( vasculitis, hemophilia , etc.);
- bleeding;
- aortic dissection , intracranial aneurysm;
- antiphospholipid syndrome;
- traumatic brain injury;
- hemorrhagic stroke;
- uncontrolled hypertension;
- liver cirrhosis , accompanied by pathological changes in the veins of the esophagus;
- threatened miscarriage;
- menstrual period;
- pregnancy;
- childbirth (including recent);
- lactation period;
- erosive and ulcerative lesions of the stomach and intestinal tract;
- recent surgical interventions on the prostate gland, brain, eyes, bile ducts and liver, as well as the condition after lumbar puncture .
Heparin injections should be prescribed with caution to patients with polyvalent allergies (including bronchial asthma ), diabetes mellitus , arterial hypertension , active tuberculosis , endo- and pericarditis , chronic renal failure, liver failure ; patients undergoing dental procedures or radiation therapy; persons over 60 years of age (especially women); women using an IUD.
Side effects
When used externally, Heparin sodium can cause skin hyperemia and hypersensitivity reactions.
When administering the solution, the following are possible:
- Hypersensitivity reactions ( drug fever , skin hyperemia, rhinitis , feeling of heat in the soles, urticaria , skin itching, collapse, bronchospasm , anaphylactic shock ).
- Headaches, dizziness, diarrhea, loss of appetite, nausea, vomiting;
- Thrombocytopenia (in approximately 6% of patients), sometimes (rarely) with death. Heparin-induced thrombocytopenia (HIT) is accompanied by: arterial thrombosis , skin necrosis and gangrene , stroke , myocardial infarction . In case of severe HIT (when the platelet is reduced to half the original number or below 100 thousand/μl), heparin should be stopped immediately.
- Local reactions ( hematoma , hyperemia , pain, ulceration, irritation at the injection site, bleeding).
- Bleeding. Typical ones are considered to be from the urinary tract and gastrointestinal tract, in areas that are subject to pressure, at the site of drug administration, from surgical wounds. Hemorrhages are also possible in various internal organs: in the retroperitoneal space, corpus luteum, adrenal glands, etc.
With long-term use of Heparin, intermittent alopecia , osteoporosis , hypoaldosteronism , soft tissues become calcified, spontaneous bone fractures occur, and the activity of liver transaminases increases.
Publications in the media
Pharmgruppa is a direct-acting anticoagulant agent. Characteristic. Polysaccharide with mol. weighing about 16 thousand Da, obtained from the lungs of cattle or the mucous membrane of the small intestine of pigs.
Pharmaceutical action. Direct anticoagulant, belongs to the group of medium molecular heparins, slows down the formation of fibrin. The anticoagulant effect is detected in vitro and in vivo and occurs immediately after intravenous administration. 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 (the ability to inhibit thrombin and activated factor X is especially important). Increases renal blood flow; increases cerebral vascular resistance, reduces the activity of cerebral hyaluronidase, activates lipoprotein lipase and has a hypolipidemic effect. Reduces the activity of 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, it can increase the activity of brain tyrosine hydroxylase, pepsinogen, DNA polymerase and reduce the activity of myosin ATPase, pyruvate kinase, RNA polymerase, pepsin. In patients with coronary artery disease (in combination with ASA), it reduces the risk of acute coronary artery thrombosis, myocardial infarction and sudden death. Reduces the frequency of recurrent infarctions and mortality in patients who have had myocardial infarction. In high doses it is effective for pulmonary embolism and venous thrombosis, in small doses it is effective for the prevention of venous thromboembolism, incl. after surgical operations. With intravenous administration, blood coagulation slows down almost immediately, with intramuscular injection - after 15-30 minutes, with subcutaneous administration - after 20-60 minutes, after inhalation the maximum effect is within 24 hours; the duration of the anticoagulation effect is respectively 4-5, 6, 8 hours and 1-2 weeks, the therapeutic effect - prevention of thrombus formation - lasts much longer. Deficiency of antithrombin III in plasma or at the site of thrombosis may reduce the antithrombotic effect of heparin.
Pharmacokinetics. After subcutaneous administration, TCmax is 4-5 hours. Bonding 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). Does not penetrate the placenta or into breast milk. It is intensively captured by endothelial cells and cells of the mononuclear-macrophage system (RES cells), concentrated in the liver and spleen. When administered by inhalation, it is absorbed by alveolar macrophages, capillary endothelium, large blood and lymphatic vessels: these cells are the main site of heparin deposition, from which it is gradually released, maintaining the required concentration in the plasma. 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), as well as the binding of heparin to the macrophage system explains the rapid biological inactivation and short duration of action. Desulfated molecules are converted into low molecular weight fragments by the action of kidney endoglycosidase. T1/2 - 1-6 hours (average - 1.5 hours); increases with obesity, liver and/or kidney failure; decreases with pulmonary embolism, infections, and malignant tumors. It is excreted by the kidneys, mainly in the form of inactive metabolites, and only with the administration of high doses is it possible to excrete (up to 50%) unchanged. Not excreted by hemodialysis.
Indications. Treatment and prevention: deep vein thrombosis, pulmonary embolism (including in diseases of the peripheral veins), coronary artery thrombosis, thrombophlebitis, unstable angina, acute myocardial infarction, atrial fibrillation (including accompanied by embolization), DIC- syndrome, prevention and therapy of microthrombosis and microcirculation disorders, renal vein thrombosis, hemolyticouremic syndrome, mitral heart disease (prevention of thrombosis), bacterial endocarditis, glomerulonephritis, lupus nephritis. Prevention of blood clotting during operations using extracorporeal circulatory methods, during hemodialysis, hemosorption, peritoneal dialysis, cytapheresis, forced diuresis, when flushing venous catheters.
Contraindications. Hypersensitivity to heparin, diseases accompanied by increased bleeding (hemophilia, thrombocytopenia, vasculitis, etc.), bleeding, cerebral aneurysm, dissecting aortic aneurysm, hemorrhagic stroke, antiphospholipid syndrome, trauma (especially traumatic brain injury), uncontrolled arterial hypertension, erosive -ulcerative lesions of the gastrointestinal tract; cirrhosis of the liver, accompanied by varicose veins of the esophagus; menstrual period, threatened miscarriage, childbirth (including recent ones), recent surgical interventions on the eyes, brain, prostate gland, liver and biliary tract, condition after spinal puncture, pregnancy, lactation.
Carefully. Persons suffering from polyvalent allergies (including bronchial asthma), arterial hypertension, dental procedures, diabetes mellitus, endocarditis, pericarditis, ICH, active tuberculosis, radiation therapy, liver failure, chronic renal failure, old age (over 60 years, especially women ). Category of action on the fetus. C
Dosing. Heparin is prescribed as a continuous intravenous infusion or as regular intravenous injections, as well as subcutaneously (into the abdominal area). For prophylactic purposes - subcutaneously, 5 thousand IU/day, at intervals of 8-12 hours. The usual place for subcutaneous injections is the anterolateral abdominal wall (in exceptional cases, it is injected into the upper region of the shoulder or thigh), in this case, a thin needle is used, which should be inserted deeply, perpendicularly, into a fold of skin, held between the thumb and index finger until the solution is administered. The injection sites should be alternated each time (to avoid the formation of a hematoma). The first injection must be performed 1-2 hours before the start of surgery; in the postoperative period, administer for 7-10 days, and if necessary, for a longer period. The initial dose of heparin administered for therapeutic purposes is usually 5 thousand IU and is administered intravenously, after which treatment is continued using intravenous infusion. Maintenance doses are determined depending on the method of administration: - with continuous intravenous infusion, 1-2 thousand IU/hour (24-48 thousand IU/day) are prescribed, diluting heparin in a 0.9% NaCl solution; — for periodic intravenous injections, 5-10 thousand IU of heparin are prescribed every 4 hours. Doses of heparin for intravenous administration are selected so that the activated partial thromboplastin time (aPTT) is 1.5-2.5 times greater than the control. With subcutaneous administration of small doses (5 thousand IU 2-3 times a day) for the prevention of thrombus formation, regular monitoring of aPTT is not required, because it increases slightly. Continuous IV infusion is the most effective way to use heparin, better than regular (periodic) injections, because provides more stable hypocoagulation and is less likely to cause bleeding. When performing extracorporeal circulation, it is administered at a dose of 140-400 IU/kg or 1.5-2 thousand IU per 500 ml of blood. During hemodialysis, 10 thousand IU are first administered intravenously, then in the middle of the procedure another 30-50 thousand IU are administered. For older people, especially women, doses should be reduced. For children, the drug is administered 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 under APTT monitoring. Side effect. Allergic reactions: skin hyperemia, drug fever, urticaria, rhinitis, itching and feeling of heat in the soles, bronchospasm, collapse, anaphylactic shock. Dizziness, headaches, nausea, loss of appetite, vomiting, diarrhea. Thrombocytopenia (6% of patients), in rare cases fatal. Against the background of heparin-induced thrombocytopenia: skin necrosis, arterial thrombosis, accompanied by the development of gangrene, myocardial infarction, stroke. If severe thrombocytopenia develops (2 times the original number or below 100 thousand / μl), heparin administration is immediately stopped. With long-term use: osteoporosis, spontaneous bone fractures, soft tissue calcification, hypoaldosteronism, transient alopecia, increased activity of “liver” transaminases. Local reactions: irritation, pain, hyperemia, hematoma and ulceration at the injection site, bleeding. Bleeding: typical - from the gastrointestinal tract and urinary tract, at the site of drug administration, in areas exposed to pressure, from surgical wounds; hemorrhages in various organs (including adrenal glands, corpus luteum, retroperitoneal space).
Overdose. Symptoms: signs of bleeding.
Treatment: for minor bleeding caused by an overdose of heparin, it is enough 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). It must 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 of protamine sulfate is 50 mg. Hemodialysis is ineffective.
Interaction. The effect of heparin is enhanced by some antibiotics (they reduce the formation of vitamin K by intestinal microflora), ASA, dipyridamole, NSAIDs and other drugs that reduce platelet aggregation (which remains the main mechanism of hemostasis in patients treated with heparin), indirect anticoagulants, drugs that block tubular secretion. Weakening - antihistamines, phenothiazines, cardiac glycosides, nicotinic acid, ethacrynic acid, tetracyclines, ergot alkaloids, nicotine, nitroglycerin (iv administration), thyroxine, ACTH, alkaline amino acids and polypeptides, protamine. Do not mix with other drugs in one syringe.
Special instructions. Heparin cannot be administered intramuscularly, because possible formation of hematomas at the injection site. The heparin solution may turn yellow, but this does not change its activity or tolerability. When prescribing heparin for therapeutic purposes, its dose is selected depending on the aPTT value. While using heparin, you should not administer other drugs intramuscularly or perform organ biopsies. To dilute heparin, only 0.9% NaCl solution is used. Although heparin does not pass into breast milk, its administration to nursing mothers in some cases caused the rapid (within 2-4 weeks) development of osteoporosis and spinal damage.
Instructions for use of Heparin (Method and dosage)
Heparin injections, instructions for use, administration features
Heparin in ampoules is prescribed in the form of:
- regular injections into a vein;
- continuous infusion;
- subcutaneously (injections in the stomach).
For preventive purposes, sodium heparin is administered subcutaneously at a dose of 5 thousand IU/day, leaving 8-12 hours between injections (to prevent thrombosis, the patient is injected with 1 ml of solution under the skin of the abdomen 2 times/day).
For medicinal purposes, the solution is infused intravenously (the method of administration is drip infusion). Dose - 15 IU/kg/h (that is, an adult with average body weight is prescribed 1 thousand IU/h).
To achieve a rapid anticoagulant effect, 1 ml of solution is injected intravenously into the patient immediately before infusion. If administration into a vein is impossible for some reason, then the medicine is injected under the skin 4 times a day. 2 ml.
The highest daily dose is 60-80 thousand IU. The use of Heparin at the indicated dose for more than 10 days is permitted only in exceptional cases.
For children, the solution is injected into a vein by drip. The dose is selected depending on age: at the age of 1 to 3 months the daily dose is 800 IU/kg, from 4 months to a year - 700 IU/kg, children over 6 years of age are prescribed (under APTT monitoring) 500 IU/kg/ days
Technique for administering Heparin, preparation for manipulation and administration of solution
Subcutaneous injections are usually given into the anterolateral wall of the abdomen (if this is not possible, the medicine can be injected into the upper thigh/shoulder area).
A thin needle is used for injection.
The first injection is given 1-2 hours before the start of the operation; in the postoperative period, the drug continues to be administered for 7-10 days (if necessary, longer).
Treatment begins with a jet injection of 5 thousand IU of heparin into a vein, after which the solution is continued to be administered using an intravenous infusion (a 0.9% NaCl solution is used to dilute the drug).
Maintenance doses are calculated depending on the route of administration.
The algorithm for administering Heparin is as follows:
- 15-20 minutes before administering the drug, apply cold to the injection site in the abdominal area (this will reduce the likelihood of bruising).
- The procedure is performed in compliance with the rules of asepsis.
- The needle is inserted into the base of the fold (the fold is held between the thumb and forefinger until the end of drug administration) at an angle of 90°.
- Do not move the tip of the needle after insertion or retract the piston. Otherwise, tissue damage and hematoma formation may occur.
- The solution should be injected slowly (to reduce pain and avoid tissue damage).
- The needle is removed easily, at the same angle at which it was inserted.
- There is no need to wipe the skin; the injection site is lightly pressed with a sterile dry swab (the swab is held for 30-60 seconds).
- It is recommended to alternate anatomical sites for injection. The areas in which injections are given during the week should be 2.5 cm apart from each other.
Heparin ointment, instructions for use
The gel is used as an external agent. It should be applied to the affected area from 1 to 3 times a day. A single dose is a column 3 to 10 cm long.
For thrombosis of hemorrhoidal veins, the drug is used rectally.
Gel-impregnated cotton pads are applied to the inflamed nodes and secured with a bandage. Gel-soaked tampons are inserted into the anus. Treatment usually lasts 3-4 days.
For leg ulcers, the ointment is carefully applied to the inflamed skin around the ulcer.
Frequency of applications - 2-3 rubles/day. Treatment is continued until the inflammation disappears. Usually the course lasts from 3 to 7 days. The doctor decides whether a longer course is necessary.
Other heparin-containing ointments are used in a similar way (for example, the instructions for Heparin-Acrigel 1000 are practically no different from the instructions for Heparin gel or Lyoton 1000 ).
For the treatment of hemorrhoids (external and internal), anal fissures , thrombophlebitis of the anal veins , as well as to relieve itching and eliminate eczema suppositories for hemorrhoids (for example, Hepatrombin G can be used as an alternative to Heparin ointment .
Additional Information
Heparin is available only in the form of a solution, ointment or gel (gel, unlike ointment, contains a larger amount of the active substance and is better absorbed into the skin).
Heparin tablets are not available because heparin is practically not absorbed from the digestive tract.
Heparin solution for intravenous and subcutaneous administration 5000 IU/ml 5 ml bottles 5 pcs. in Moscow
For medicinal purposes
Heparin is prescribed as a continuous intravenous infusion or as regular intravenous injections, as well as subcutaneously (in the abdomen).
For preventive purposes
— subcutaneously, 5000 IU/day, at intervals of 8–12 hours. The usual place for subcutaneous injections is the anterolateral abdominal wall (in exceptional cases, it is injected into the upper region of the shoulder or thigh), using a thin needle, which should be inserted deeply, perpendicularly , into a fold of skin, held between the thumb and index finger until the solution is injected. The injection sites should be alternated each time (to avoid the formation of a hematoma). The first injection must be performed 1–2 hours before the start of surgery; in the postoperative period - administered for 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 intravenously, after which treatment is continued using subcutaneous injections or intravenous infusions.
Maintenance doses are determined depending on the route of administration:
- for continuous intravenous infusion, 1000–2000 IU/hour (24000–48000 IU/day) is prescribed, diluting heparin with 0.9% sodium chloride solution;
- with regular intravenous injections, 5000–10000 IU of heparin is prescribed every 4–6 hours;
- for subcutaneous administration, 15,000–20,000 IU is administered every 12 hours or 8,000–10,000 IU every 8 hours.
Intravenous injections are recommended only for initial doses or if for some reason intravenous infusion or subcutaneous administration cannot be used. Repeated intravenous injections cause significant fluctuations in hemostasis and more often cause dangerous bleeding, so they are prescribed only when absolutely necessary.
For adults with thrombosis of mild to moderate severity, it is administered intravenously, 40,000–50,000 IU/day for 3–4 administrations; for severe thrombosis and embolism - 20,000 IU intravenously 4 times a day with an interval of 6 hours.
For health reasons, 25,000 IU is administered intravenously once, then 20,000 IU every 4 hours until a daily dose of 80,000–120,000 IU is reached. When administered intravenously, at least 40,000 IU is added to the daily volume of infusion solution.
The duration of heparin therapy depends on the indications and route of administration. For intravenous use, the optimal duration of treatment is 7–10 days, after which therapy is continued with oral anticoagulants (it is recommended to prescribe oral anticoagulants starting from the 1st day of heparin treatment or from 5 to 7 days, and stop the use of heparin on the 4–5 day of combination therapy) . In case of extensive thrombosis of the iliofemoral veins, it is advisable to carry out longer courses of treatment with heparin.
Laboratory monitoring of the effectiveness and safety of sodium heparin therapy
The dose of heparin sodium should be adjusted based on laboratory blood clotting parameters. When using heparin sodium, it is necessary to monitor the activated partial thromboplastin time (aPTT) or blood clotting time (BCT). The dose of heparin sodium administered is considered adequate if the aPTT is 1.5 to 2.0 times the normal value or if the patient's ICR is 2.5 to 3.0 times the control value.
With continuous intravenous infusion of heparin sodium, it is recommended to determine the initial aPTT, then determine the aPTT every 4 hours, followed by increasing or decreasing the rate of infusion of heparin sodium until the target aPTT level is achieved (1.5-2 times normal), then determine the aPTT every 6 hours .
When bolus intravenous administration of heparin sodium is recommended, it is recommended to determine the initial aPTT, then determine the aPTT before each bolus, followed by an increase or decrease in the administered dose of heparin sodium.
When administering sodium heparin subcutaneously, it is recommended to monitor the aPTT 4–6 hours after injection, followed by an increase or decrease in the administered dose of sodium heparin.
When using sodium heparin in low doses to prevent thromboembolic complications, it is not necessary to monitor the aPTT.
Continuous intravenous infusion is the most effective way of using sodium heparin, better than regular (periodic) injections, because provides more stable hypocoagulation and is less likely to cause bleeding.
Use of heparin sodium in special clinical situations
Primary percutaneous coronary angioplasty for acute coronary syndrome without ST segment elevation and myocardial infarction with ST segment elevation: sodium heparin is administered intravenously as a bolus at a dose of 70–100 IU/kg (if the use of glycoprotein IIb/IIIa receptor inhibitors is not planned) or at a dose of 50 –60 IU/kg (when used together with inhibitors of glycoprotein IIb/IIIa receptors).
Thrombolytic therapy for ST-segment elevation myocardial infarction: sodium heparin is administered as an intravenous bolus at a dose of 60 IU/kg (maximum dose 4000 IU), followed by intravenous infusion at a dose of 12 IU/kg (not more than 1000 IU/hour) for 24– 48 hours. The target APTT level is 50–70 sec or 1.5–2.0 times higher than normal; APTT monitoring 3, 6, 12 and 24 hours after the start of therapy.
Prevention of thromboembolic complications after surgery using low doses of sodium heparin:
subcutaneously, deep into the fold of the skin of the abdomen. The initial dose is 5000 IU 2 hours before surgery. In the postoperative period: 5000 IU every 8–12 hours for 7 days or until the patient’s mobility is completely restored (whichever comes first). When using sodium heparin in low doses to prevent thromboembolic complications, it is not necessary to monitor the aPTT.
When preventing thrombus formation in the postoperative period, the first injection should be performed 1–2 hours before the start of surgery; in the postoperative period, administer for 7–10 days, and, if necessary, for a longer period.
Application in cardiovascular surgery during operations using extracorporeal circulatory systems:
the initial dose of sodium heparin is not less than 150 IU/kg body weight. Next, sodium heparin is administered by continuous intravenous infusion at a rate of 15–25 drops/min, 30,000 IU 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 expected duration of the operation is 60 minutes or more).
Use in hemodialysis:
Initial dose of heparin sodium: 25–30 IU/kg (or 10,000 IU) intravenous bolus, then continuous infusion of heparin sodium 20,000 IU/100 mg sodium chloride solution at a rate of 1500–2000 IU/hour (unless otherwise indicated in the instructions for use of the systems for hemodialysis).
Application in pediatrics:
Adequate controlled studies of the use of heparin sodium in children have not been conducted. The recommendations presented are based on clinical experience.
Initial dose: 75–100 IU/kg IV bolus over 10 minutes.
Maintenance dose: children aged 1-3 months - 25-30 IU/kg/hour (800 IU/kg/day), children aged 4-12 months - 25-30 IU/kg/hour (700 IU/kg/day day), children over 1 year - 18–20 IU/kg/hour (500 IU/kg/day) intravenously.
The dose of heparin sodium should be adjusted based on coagulation parameters (target aPTT 60–85 seconds).
Switching to warfarin therapy: To ensure a sustained anticoagulant effect, therapy with heparin sodium at full dose should be continued until a stable target INR level is achieved. After this, the administration of sodium heparin must be stopped.
Switching to dabigatran therapy: Continuous intravenous heparin sodium should be discontinued immediately after the first dose of dabigatran. With divided intravenous administration, the patient should take the first dose of dabigatran orally 1–2 hours before the scheduled administration of the next dose of sodium heparin.
Overdose
Symptoms of overdose with parenteral use are bleeding of varying severity.
Treatment: for minor bleeding caused by an overdose of the drug, it is enough to stop using it. If bleeding is extensive, protamine sulfate (1 mg per 100 IU of heparin) is used to neutralize excess heparin.
Please note that heparin is eliminated quickly. Thus, if protamine sulfate is administered 30 minutes after the previous dose of heparin, it should be administered at half the dose; The highest dose of protamine sulfate is 50 mg.
It is not excreted by hemodialysis.
Cases of overdose with external use of the drug have not been described. Due to the low systemic absorption of the drug, an overdose is considered unlikely. With prolonged use on large surfaces, hemorrhagic complications .
Treatment: discontinuation of the drug, if necessary, use of a one percent solution of protamine sulfate (heparin antagonist).
Interaction
Drugs that block tubular secretion, indirect anticoagulants that reduce the formation of vitamin K by intestinal microflora, antibiotics, NSAIDs, dipyridamole , ASA and other drugs that reduce platelet aggregation enhance the effect of heparin.
The weakening of the effect is facilitated by: cardiac glycosides , ergot alkaloids , phenothiazines , antihistamines, nicotine , ethacrynic and nicotinic acids , nitroglycerin (iv administration), ACTH, tetracyclines , alkaline amino acids and polypeptides, thyroxine , protamine .
Do not mix the solution in the same syringe with other medications.
When applied topically, the anticoagulant effect of the drug is enhanced when the gel is used in combination with antiplatelet agents, NSAIDs, and anticoagulants. Tetracycline , thyroxines , nicotine and antihistamines reduce the effect of heparin.
special instructions
Due to the risk of hematoma formation at the injection site, the solution should not be injected into the muscle.
The solution may acquire a yellowish tint, which does not affect its activity or tolerability.
When prescribing the drug for therapeutic purposes, the dosage should be selected taking into account the aPTT value.
During treatment with the drug, organ biopsies and other medications should not be administered intramuscularly.
To dilute the solution, only 0.9% NaCl solution can be used.
The gel should not be applied to mucous membranes or open wounds. In addition, it is not used in the presence of purulent processes. The use of ointment is not recommended for DVT.
Unfractionated Heparin
Heparin with an average molecular weight of 12-16 thousand daltons, which is isolated from bovine lung or the mucous membrane of the intestinal tract of pigs, is called unfractionated. It is used in the production of drugs that have local and systemic effects (heparin containing ointments and solutions for parenteral administration).
The drug, through interaction with AT III (indirectly), inhibits the main enzyme of the blood coagulation system, as well as other coagulation factors, and this in turn leads to antithrombotic and anticoagulation effects.
Endogenous heparin in the human body can be found in muscles, intestinal mucosa, and lungs. In structure, it is a mixture of glycosaminoglycan fractions, which consist of sulfatide residues of D-glucosamine and D-glucuronic acid with a molecular weight of 2 to 50 thousand daltons.
Fractionated Heparin
Fractionated (low molecular weight) heparins are obtained by enzymatic or chemical depolymerization of unfractionated heparins. This Heparin consists of polysaccharides with an average molecular weight of 4-7 thousand daltons.
LMWHs are characterized as weak anticoagulants and highly effective direct-acting antithrombotics. The action of such drugs is aimed at compensating hypercoagulation processes.
LMWH begins to act immediately after administration, while its antithrombotic effect is pronounced and prolonged (the drug is administered only 1 time per day).
Classification of low molecular weight Heparins:
- drugs used to prevent thrombosis/thromboembolism ( Klivarin , Troparin , etc.);
- drugs used to treat unstable angina and MI without a pathological Q wave, thrombosis and thromboembolism , acute DVT, PE ( Fragmin , Clexane , Fraxiparine );
- drugs used to treat severe vein thrombosis ( Fraxiparine Forte );
- drugs used to prevent thrombus formation and coagulation during hemofiltration and hemodialysis ( Fraxiparine , Fragmin , Clexane ).
Heparin sodium
Dosage form
Gel for external use
Composition per 100 g
Active substance
: sodium heparin – 100,000 IU.
Excipients
: carbomer 940 – 1.25 g, methyl parahydroxybenzoate – 0.12 g, propyl parahydroxybenzoate – 0.03 g, ethanol 96% – 30.00 ml, orange flower oil – 0.05 g, lavender oil – 0.05 g, trolamine (triethanolamine) – 0.85 g, purified water – up to 100.00 g.
Description
Colorless or with a slightly yellowish tint, almost transparent gel with a viscous consistency and a characteristic odor.
Pharmacotherapeutic group
Direct acting anticoagulant for topical use
ATX code: S05BA03
Pharmacological properties
Pharmacodynamics
Heparin sodium is a direct anticoagulant, belongs to the group of medium molecular heparins. Prevents thrombus formation, inhibits the activity of hyaluronidase, and activates the fibrinolytic properties of blood.
When applied externally, it has a local antithrombotic, anti-edema and anti-inflammatory effect, improves blood microcirculation and activates tissue metabolism, as a result of which the processes of resorption, hematomas are accelerated, the formation of blood clots is prevented, and tissue swelling is reduced.
Pharmacokinetics
A small amount of heparin is absorbed from the skin surface into the systemic circulation. The maximum concentration of the drug in the blood is observed 8 hours after application. Heparin is eliminated primarily through the kidneys, with a half-life of 12 hours. Does not penetrate the placental barrier.
Indications for use
— diseases of the superficial veins: varicose veins, chronic venous insufficiency and related complications (thrombophlebitis, periphlebitis);
- blunt injuries and bruises of soft tissues;
— subcutaneous hematomas, including hematomas after venous surgery, phlebectomy:
- localized infiltrates and swelling of soft tissues.
Contraindications
- hypersensitivity to the components of the drug;
— violation of the integrity of the skin at the site of application of the drug (ulcerative-necrotic changes in the skin);
— traumatic violations of the integrity of the skin (open wounds);
- increased tendency to bleeding, thrombocytopenia;
- age under 18 years (the safety and effectiveness of the drug have not been studied).
Use during pregnancy and breastfeeding
The use of the drug is possible during pregnancy and breastfeeding if the expected benefit to the mother outweighs the potential risk to the fetus and child.
Heparin does not penetrate the placental barrier and into breast milk. Due to the insignificant absorption of heparin when applied externally, the drug does not have a systemic effect on the body. However, before using the drug, you should consult your doctor.
Directions for use and doses
Externally.
A small amount of gel (3-10 cm) 1-3 times a day is applied in a thin layer to the affected area and gently rubbed into the skin.
For diseases of the superficial veins:
for initial symptoms of venous insufficiency (“heaviness”, pain in the legs, venous edema) use for 1-3 weeks depending on the severity of the symptoms;
for chronic venous insufficiency, use for 4-6 weeks depending on the severity of symptoms, use no more than 6 weeks.
For blunt injuries and soft tissue bruises: course of treatment for 5-7 days or until symptoms disappear, use no more than 10 days.
For subcutaneous hematomas. including hematomas after vein surgery, phlebectomy: course of treatment for 7-21 days or until symptoms disappear, apply for no more than 4 weeks.
For localized infiltrates and swelling of soft tissues: treatment course is 4-6 weeks or until symptoms disappear, use no more than 6 weeks.
The need for further treatment is determined by the doctor.
If there is no improvement during the treatment period, or the symptoms worsen, or new symptoms appear, you should consult your doctor. Use the drug only according to the indications, method of administration and in the doses indicated in the instructions.
Side effect
In very rare cases (< 1/10000), when used externally, hypersensitivity reactions to heparin are possible. In some cases (frequency unknown: cannot be estimated from the available data), allergic reactions to the components of the drug may occur, manifested by redness of the skin and/or itching, which usually disappear after stopping use of the drug. If you experience the side effects listed in the instructions, or they get worse, or you notice any other side effects not listed in the instructions, tell your doctor.
Overdose
The extremely low systemic absorption of the active component of the drug when applied externally makes overdose almost impossible.
In case of overdose, the effect of heparin can be neutralized with a solution of protamine sulfate.
Interaction with other drugs
With long-term use of heparin on large areas of the skin and simultaneous use of indirect anticoagulants (warfarin, acenocoumarol, etc.), prothrombin time and blood clotting time should be monitored.
It is not recommended to mix with other products for external use. Concomitant use with drugs for external use containing tetracyclines, antihistamines or non-steroidal anti-inflammatory drugs is not recommended. If you are using the above or other medications (including over-the-counter medications), consult your doctor before using Heparin Sodium.
special instructions
It is not recommended to apply to mucous membranes, open wounds and use in the presence of purulent lesions at the intended site of application of the gel.
With prolonged use of the drug on large areas of the skin and the simultaneous use of indirect anticoagulants (warfarin, syncumar, etc.), prothrombin time and blood clotting time should be monitored.
It is not recommended to use the drug for deep vein thrombosis.
Methyl parahydroxybenzoate and propyl parahydroxybenzoate included in the drug can cause allergic reactions (including delayed ones).
The effect of the drug on the ability to drive vehicles and machinery
The use of the drug does not affect the ability to drive vehicles or engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Release form
Gel for external use 1000 IU/g.
20, 25, 30, 35, 40, 50, 60, 70, 80, 100 g in aluminum tubes, sealed with a low-density polyethylene bushon.
Each tube, along with instructions for use, is placed in a cardboard pack. It is allowed to pack tubes without a pack from 9 to 300 pieces with an equal number of instructions for medical use in a group package (for hospitals).
Storage conditions
At a temperature not higher than 25 °C.
Keep out of the reach of children.
Best before date
5 years.
Do not use after the expiration date stated on the packaging.
Vacation conditions
Available without a prescription.
Analogs
Level 4 ATC code matches:
Girudoproct
Heparoid Zentiva
Heparin ointment
Gepatrombin G
Lyoton
Trombless
Venolife
Hepatrombin
Gel analogues: Heparin-Acrigel 1000 , Lyoton 1000 , Lavenum , Trombless .
Generic injection forms: Heparin J , Heparin-Ferein , Heparin-Sandoz .
Drugs with a similar mechanism of action: tablets - Piyavit , Angioflux , Wessel Due F ; solution - Angioflux , Hemapaxan , Antithrombin III human , Wessel Due F , Fluxum , Anfibra , Fraxiparine , Enixum .
Use during pregnancy and lactation
Heparin solution is not contraindicated for pregnant women. However, despite the fact that the active substance of the drug does not penetrate into milk, its use in nursing mothers in some cases led to the rapid (within 2-4 weeks) development of osteoporosis and spinal damage.
The feasibility of use should be decided individually, taking into account the risk to the fetus/benefit to the mother ratio.
There are no data on the use of the gel during pregnancy and lactation.
Vacuum tubes with sodium heparin
Sodium heparin is used in cosmetology for plasma therapy. The drug in dry form, together with a special gel, is applied to the inner wall of a tube with sodium heparin.
The amount of powder is calculated strictly according to the instructions, namely 12-30 IU per 1 ml of blood. This procedure allows the injection of a tube of sodium heparin to be separated into a cellular component and platelet-rich plasma within two days.
Vacuum tubes with sodium heparin have many advantages, namely:
- with the same amount of blood you can get a larger volume of plasma;
- virtually no risks associated with abnormal blood parameters;
- the additional use of a special gel allows the formation of a protective barrier between the cellular component and plasma during the process in a centrifuge
Reviews
Heparin is an effective and well-studied antithrombotic agent , the mechanism of action of which is to suppress the activity of thrombin , which catalyzes the biotransformation of fibrinogen into fibrin and a number of other reactions in the hemostatic system.
Most often, the external use of gel and ointment forms of the drug is discussed on the Internet. Reviews of heparin-containing ointments and gels (in particular, reviews of Heparin Acrigel 1000 ) are overwhelmingly positive: such drugs really help with bruises, thrombophlebitis and hemorrhoids , and also remove localized infiltrates well.
Vacuum tubes with lithium heparin
Also, lithium heparin has found wide application in cosmetology, namely during plasma therapy procedures. The effect of lithium heparin applied to the inside of the tube is also to prevent blood clotting.
This result with Li heparin is achieved due to the ability of the drug to inhibit the activity of thrombin and inhibit the process of converting fibrinogen to fibrin. The advantages of Li heparin include the minimal risk of hemolysis.
In our online store you can purchase a wide range of tubes with Na / Li heparin at low prices. Contact us!
Heparin price
The average price of Heparin injections in Ukrainian pharmacies is from 180 to 226 UAH (5 ml ampoules, No. 5). You can buy Heparin ointment for an average of 35 UAH. The price of Heparin Acrigel 1000 in Ukraine is about 250 UAH.
In Russian pharmacies, sodium heparin in ampoules can be purchased for 360-550 rubles. The price of Heparin gel is 260-300 rubles.
- Online pharmacies in RussiaRussia
- Online pharmacies in UkraineUkraine
- Online pharmacies in KazakhstanKazakhstan
ZdravCity
- Heparin ointment 25g n1Altaivitamins JSC
RUB 63.order - Heparin-Akrikhin 1000 gel 1 thousand. IU/1g 30gAO Akrikhin
RUB 390 order
- Heparin-Akrikhin 1000 gel for external use. approx. 1000 IU/g tube 50g JSC AKRIKHIN
416 RUR order
- Heparin ointment 25g Belmedpreparaty RUP Belmedpreparaty
70 rub. order
- Heparin ointment 25g NizhpharmAO "Nizhpharm"
82 RUR order
Pharmacy Dialogue
- Heparin-Akrikhin gel 1000IU/g 30gAkrikhin OJSC
405 rub. order
- Heparin ointment (tube 25g) Nizhpharm JSC
80 rub. order
- Heparin-Akrikhin gel (gel 1000EM/g 50g) Akrikhin JSC
RUR 459 order
- Heparin (vial IV and SC injection 5tIU/ml 5ml No. 5) Ozon LLC
RUB 1,700 order
- Heparin (vial IV and SC injection 5tIU/ml 5ml No. 5) Belmedpreparaty
RUB 1,586 order
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Pharmacy24
- Heparin-Darnitsa 600 units 30 g gel PrAT" Pharmaceutical company "Darnitsa", Ukraine
62 UAH. order - Heparin ointment 25 g TOV DKP Pharm.Fabrika, Ukraine
46 UAH order
- Heparin-Indar 5000 MO/ml 5 ml (25000 MO) No. 1 solution PrAT “On the production of insulin” Indar”, m. Kiev, Ukraine
34 UAH order
- Heparin-Novopharm 5000 MO/ml 5 ml No. 5 solution Novofarm-Biosintez TOV, Novograd-Volinsky, Ukraine
256 UAH order
PaniPharmacy
- Heparin ointment Heparin ointment 25g tube Ukraine, Zhytomyr FF LLC
60 UAH.order
- Heparin gel Heparin gel 30g Ukraine, Darnitsa ChAO
68 UAH order
- Heparin bottle Heparin solution d/in. 5000U/ml 5ml vial. №5 Ukraine, Pharmstandard-Biolek
166 UAH order
- Heparin solution d/in. 25000U/ml 5ml No.1 Ukraine, INDAR
39 UAH order
- Heparin bottle Heparin-Novopharm solution d/in 5000 MO bottle. 5ml. No.5 Ukraine, Novofarm-Biosintez LLC
268 UAH order
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