Instructions Heparin-Pharmex solution for injection 5000 IU/ml bottle 5 ml No. 5
Composition
active ingredient: 1 ml of solution contains heparin sodium 5000 IU;
Excipients: benzyl alcohol, sodium chloride, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: clear, colorless or yellowish solution.
Pharmacotherapeutic group
Antithrombotic agents. Heparin group. ATC code B01A B01.
Pharmacological properties
Pharmacodynamics.
Heparin is a glycosaminoglycan (mucopolysaccharide) consisting of sulfated residues of D-glucosamine and D-glucuronic acid.
Heparin is a direct-acting anticoagulant. In solution, heparin has a negative charge, which facilitates its interaction with proteins involved in the blood clotting process. Heparin binds to antithrombin III (heparin cofactor) and inhibits the blood clotting process by inactivating factors V, VII, IX, X. In this case, factors that activate blood clotting (kallikrein, IXa, Xa, XIa, XIIa) are neutralized, and the transition of prothrombin to thrombin is disrupted. When the process of thrombus formation has already begun, large amounts of heparin can inhibit further coagulation by inactivating thrombin and inhibiting the conversion of fibrinogen to fibrin. Heparin also prevents the formation of stable fibrin clots by inhibiting the activation of fibrin stabilizing factor. When administered parenterally, heparin slows blood clotting, activates the fibrinolysis process, inhibits the activity of certain enzymes (hyaluronidase, phosphatase, trypsin), slowing the effect of prostacyclin on platelet aggregation caused by the action of adenosine diphosphate.
Pharmacokinetics.
After intravenous infusion, the maximum level in the blood plasma is reached after a few minutes, after slow intravenous infusion - no later than after 2-3 minutes, after subcutaneous - after 40-60 minutes. The volume of distribution of heparin corresponds to the volume of blood plasma and increases significantly with increasing dose of the drug. Blood plasma proteins at a heparin concentration of 2 IU/ml of blood bind up to 95% of the drug, at higher concentrations - less. Heparin is partially metabolized in the liver. About 20% is found in the urine in the form of unchanged heparin and uroheparin (has an activity of 50% of the active substance). The biological half-life is 1.32-1.72 hours. The half-life from blood plasma is 30-60 minutes. In liver failure, heparin accumulates. Heparin does not penetrate into breast milk and does not penetrate the placenta well.
Indication
– Prevention and treatment of thromboembolic diseases and their complications (acute coronary syndrome, thrombosis and embolism of major veins and arteries, cerebral vessels, eyes, phase I of disseminated intravascular coagulation syndrome, permanent form of atrial fibrillation with embolization);
– for the prevention of postoperative venous thrombosis and pulmonary embolism (in a low-dose regimen) in patients who have undergone surgery or who are at risk of developing thromboembolic disease for any other reason;
– to prevent blood clotting during laboratory tests, dialysis, extracorporeal circulation, heart and vascular surgeries, and direct blood transfusion.
Contraindication
Hypersensitivity to heparin and/or benzyl alcohol; hemophilia; hemorrhagic diathesis; suspected heparin-induced immune thrombocytopenia; peptic ulcer of the stomach and duodenum; severe arterial hypertension; cirrhosis of the liver, accompanied by varicose veins of the esophagus; severe renal and hepatic failure; bacterial endocarditis; menstruation; recent surgical interventions, especially neurosurgical and ophthalmological; ulcerative colitis; malignant neoplasms; hemorrhagic stroke (first 2-3 days); craniocerebral injuries; retinopathy; hemorrhage in the eye tissue; destructive pulmonary tuberculosis; encephalomalacia; hemorrhagic pancreatic necrosis; bleeding of any localization (open stomach ulcer, intracranial bleeding), with the exception of hemorrhage resulting from embolic infarction of the lungs (hemoptysis) or kidneys (hematuria); repeated bleeding in history, regardless of localization; increased vascular permeability (for example, in Werlhof's disease); state of shock; threat of abortion.
Heparin should not be used: in patients who have consumed high doses of alcohol; in the form of intramuscular injections; in acute and chronic leukemias; in aplastic and hypoplastic anemias; in acute aneurysm of the heart and aorta; during operations on the brain or spinal cord, eyeball, ears; after surgical operations in areas where the development of bleeding is dangerous for the patient's life; in diabetes mellitus; during epidural anesthesia during childbirth. For patients who are using heparin for therapeutic purposes, conduction anesthesia is contraindicated during planned surgical operations, since the use of heparin in rare cases can cause epidural or spinal hematomas, as a result of which long-term or irreversible paralysis may develop.
Interaction with other medicinal products and other types of interactions
Anticoagulants of direct and indirect action enhance the effect of heparin. Antihistamines and digitalis preparations, tetracyclines, nicotine, nitroglycerin, corticotropin, thyroxine weaken the anticoagulant effect of the drug. Agents that reduce platelet aggregation (acetylsalicylic acid, dextrin, phenylbutazone, ibuprofen, metindol, dipyridamole, hydroxychloroquine, fibrinolytics, ascorbic acid, ergot alkaloids, indomethacin, sulfinpyrazone, probenecid, cephalosporins, ketorolac, epoprostinol, clopidogrel, ticlopidine, streptokinase, intravenous administration of penicillins, ethacrynic acid, cytostatics), with simultaneous therapy with heparin can cause hemorrhages, so they should be used very carefully. The risk of bleeding is also increased with combined heparin therapy with ulcerogenic, immunosuppressive, and thrombolytic drugs.
Heparin can displace phenytoin, quinidine, propranolol, benzodiazepines and bilirubin from plasma protein binding sites. With simultaneous use, alkaline drugs, enalaprilat, tricyclic antidepressants can bind to heparin, which leads to a mutual decrease in effectiveness.
ACE inhibitors, angiotensin II antagonists: possible development of hyperkalemia.
Alcohol: simultaneous consumption of alcoholic beverages significantly increases the risk of bleeding.
Application features
When prescribing heparin for therapeutic purposes, it is forbidden to administer the drug intramuscularly. Biopsies, epidural anesthesia and diagnostic lumbar punctures should be avoided.
Use with caution in patients who have previously had hypersensitivity reactions to low molecular weight heparins.
Platelet counts should be determined before treatment, on the first day of treatment, and every 3-4 days during the entire period of heparin administration. A sudden decrease in platelet counts requires immediate discontinuation of the drug and further investigation to clarify the etiology of thrombocytopenia. If heparin-induced thrombocytopenia type I or II is suspected, heparin treatment should be discontinued.
When switching from heparin therapy to indirect anticoagulants, heparin can be discontinued only when indirect anticoagulants provide an increase in prothrombin time to therapeutic limits for at least 2 consecutive days.
In order to prevent significant hypocoagulation, the dose of heparin should be reduced without increasing the intervals between injections.
When using heparin, it is recommended to monitor hematological parameters, as well as observe the patient's clinical condition and the features of the development of hemorrhagic complications.
In patients over 60 years of age, heparin may cause hemorrhage, especially in women and in patients with impaired renal function.
Patients sensitive to animal proteins may also be sensitive to heparin.
If a hypersensitivity reaction is suspected, a diluted test dose of 1000 IU should be administered slowly intravenously a few minutes before the full dose.
Special care should be taken within 36 hours after delivery.
In patients with hypertension, blood pressure should be monitored.
In patients with diabetes mellitus, renal failure, metabolic acidosis, increased blood potassium concentration or those taking potassium supplements, it is recommended to constantly monitor blood potassium levels during use of the drug, given the increased risk of developing hyperkalemia.
Use during pregnancy or breastfeeding
Heparin is not contraindicated in pregnancy. The drug does not cross the placenta. Although heparin does not penetrate into breast milk, its administration to nursing mothers has in some cases caused rapid (within 2-4 weeks) development of osteoporosis and spinal damage. The feasibility of using the drug is determined individually, taking into account the benefit to the mother/risk to the fetus ratio.
Ability to influence reaction speed when driving vehicles or other mechanisms
There is no data on the effect of heparin on the reaction rate when driving or working with other mechanisms.
Method of administration and doses
Heparin-Pharmex is prescribed as a jet or intermittent intravenous or subcutaneous injection. Before prescribing the drug, it is necessary to determine the blood clotting time, thrombin and activated partial thromboplastin time, and platelet count. Only 0.9% sodium chloride solution is used to dilute heparin.
For the prevention of acute thrombosis, Heparin-Farmex is administered subcutaneously at 5000 IU every 6-8 hours. In the first phase of disseminated intravascular coagulation (DIC) syndrome in adults, heparin is administered subcutaneously for a long time in a daily dose of 2500-5000 IU with thrombin time control. 1-2 days before discontinuation of Heparin-Farmex, the daily dose is gradually reduced.
During open-heart surgery with the connection of an extracorporeal circulation machine, patients are administered Heparin-Pharmex in an initial dose of at least 150 IU per 1 kg of body weight. When the procedure lasts less than 60 minutes, a dose of 300 IU/kg is prescribed, and when the procedure lasts more than 60 minutes, 400 IU/kg is prescribed.
For prophylactic purposes, Heparin-Pharmex is administered subcutaneously at a dose of 5000 IU 2 hours before surgery, then 5000 IU every 6-8 hours for 7 days.
As a supplement to streptokinase, Heparin-Pharmex 5000 IU 3 times a day or 10000-12500 IU 2 times a day is indicated for patients at increased risk of developing thrombolytic complications:
– with repeated myocardial infarction;
– with a permanent form of atrial fibrillation with embolization.
In acute coronary syndrome (unstable angina or myocardial infarction), 5000 IU of Heparin-Pharmex are initially administered intravenously by jet, then switched to intravenous drip administration of the drug at a rate of 1000 IU/h. The infusion rate must be selected in such a way that during the first 2-3 days the activated partial thromboplastin time is maintained at a level 1.5-2 times higher than its normal value.
Heparin-Pharmex is prescribed to children according to the following scheme: the initial dose is 50 IU/kg (intravenous injection/infusion), the maintenance dose is 100 IU/kg every 4 hours. The average daily dose for children is 300 IU/kg.
Infants are given 2 to 10 IU/kg/h intravenously (continuously or intermittently). Subcutaneously, infants are given heparin in a daily dose of 200-300 IU/kg, divided into 4-6 injections.
In all cases, when using Heparin-Pharmex, indirect anticoagulants are prescribed 1-3 days before its discontinuation.
Children
Children are dosed according to their body weight. Do not use in premature babies and newborns. Allergic reactions, including toxic ones, may develop in children under 3 years of age.
Overdose
In case of overdose, bleeding may occur. In case of minor bleeding, it is sufficient to reduce the dose of the drug or temporarily stop its administration. In case of significant bleeding, heparin administration should be urgently canceled and an antidote should be prescribed - 1% protamine sulfate solution (injected slowly intravenously) based on the calculation that 1 mg of protamine sulfate neutralizes 85 IU of heparin.
Adverse reactions
The most common adverse reactions include hemorrhage, elevated liver enzymes, reversible thrombocytopenia, and various dermatological disorders. Isolated cases of generalized allergic reactions, skin necrosis, and priapism have also been reported.
From the blood system: thrombocytopenia type I and II, epidural and spinal hematomas.
Psychiatric: depression.
From the nervous system: headache.
From the digestive tract: nausea, vomiting, diarrhea.
On the part of the hepatobiliary system: increased levels of hepatic transaminases (ALT and AST), lactate dehydrogenase, gamma-glutamyltransferase and hyperlipidemia (these disorders are reversible and disappear upon discontinuation of the drug).
Skin and subcutaneous tissue disorders: rash (erythematous, maculopapular), urticaria, pruritus, itching and burning sensation on the skin of the feet, skin necrosis, erythema multiforme, alopecia.
Musculoskeletal system: osteoporosis, bone demineralization.
From the reproductive system: priapism.
On the part of the immune system: skin rashes, conjunctivitis, lacrimation, rhinitis, bronchospasm, asthma, tachypnea, cyanosis, allergic angiospasm in the extremities, anaphylactoid reactions, anaphylactic shock.
On the part of the endocrine system and metabolism: hypoaldosteronism, hyperkalemia, increased thyroxine levels, decreased cholesterol levels, increased blood glucose levels.
Cardiovascular system: hemorrhages and hematomas in any organ or organ system (subcutaneous, intramuscular, retroperitoneal, nasal, intraintestinal, gastric, uterine).
Injection site reactions: irritation, ulceration, tenderness, hemorrhage, hematoma, and atrophy at the injection sites.
Others: runny nose, fever.
Thrombocytopenia as a complication of heparin therapy occurs in 6% of patients. It can occur as a direct consequence of platelet aggregation under the influence of heparin or as a result of an immune reaction when the antibody affects platelets and endothelium. Reactions of the first type, as a rule, manifest themselves in a mild form and disappear after cessation of therapy, and reactions of the second type are severe. As a result of thrombocytopenia, skin necrosis and thrombosis in the arteries ("white clot") may occur, which are accompanied by recurrence of venous thromboembolism, the development of gangrene, myocardial infarction, stroke. If severe thrombocytopenia occurs (a decrease in the number of platelets by 2 times from the initial number), it is necessary to stop using heparin.
There may be an increase in transaminase activity (ALT and AST), free fatty acid levels and thyroxine; reversible potassium retention.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Incompatibility
Dobutamine hydrochloride and heparin should not be mixed and administered intravenously together because chelate complexes are formed.
Packaging
1 ml or 5 ml in vials, 5 vials in a blister pack. 1 blister pack in a cardboard box.
Vacation category
According to the recipe.
Producer
LLC "PHARMEX GROUP".
Location of the manufacturer and address of its place of business
Ukraine, 08300, Kyiv region, Boryspil city, Shevchenko st., 100.
