Heparistan (Solution) Instructions for Use

Marketing Authorization Holder

B-PHARM, LLC (Russia)

Manufactured By

B-PHARM, LLC (Russia)

Or

Kursk Biopharmaceutical Plant – Firm “Biok”, FKP (Russia)

ATC Code

B01AB01 (Heparin)

Active Substance

Heparin sodium (Rec.INN registered by WHO)

Dosage Form

Heparistan

Solution for intravenous and subcutaneous administration 5000 IU/1 ml: amp. 5 ml 5 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and subcutaneous administration transparent, from colorless to light yellowish or yellowish-brownish in color.

Excipients: benzyl alcohol – 9 mg, sodium chloride – 3.4 mg, water for injection – up to 1 ml.

5 ml – ampoules of colorless glass (5) – contour cell packaging (1) – cardboard packs.

Clinical-Pharmacological Group

Direct-acting anticoagulant – medium molecular weight heparin

Pharmacotherapeutic Group

Direct-acting anticoagulant agent

Pharmacological Action

Direct-acting anticoagulant, belongs to the group of medium molecular weight heparins. In blood plasma, it activates antithrombin III, accelerating its anticoagulant action. It disrupts the conversion 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 (anti-factor Xa) to anticoagulant activity (APTT) is 1:1.

It increases renal blood flow; increases the resistance of cerebral vessels, reduces the activity of cerebral hyaluronidase, activates lipoprotein lipase and has a hypolipidemic effect. It 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 enhances 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 of the presence of immunosuppressive activity in heparin.

In patients with coronary artery disease (in combination with acetylsalicylic acid), it reduces the risk of acute coronary artery thrombosis, myocardial infarction, and sudden death. It reduces the frequency of recurrent infarctions and mortality in patients who have had a myocardial infarction. In high doses, it is effective for pulmonary embolism and venous thrombosis; in low doses – for the prevention of venous thromboembolism, including after surgical operations.

With intravenous administration, blood coagulation slows down almost immediately; with intramuscular administration – after 15-30 minutes; with subcutaneous administration – after 20-60 minutes; after inhalation, the maximum effect is after 24 hours; the duration of the anticoagulant effect is 4-5, 6, 8 hours and 1-2 weeks, respectively; the therapeutic effect – prevention of thrombus formation – lasts significantly longer. A deficiency of antithrombin III in the plasma or at the site of thrombosis may reduce the antithrombotic effect of heparin.

Pharmacokinetics

After subcutaneous administration, the C_max of the active substance in plasma is observed after 3-4 hours. Heparin poorly penetrates the placenta due to its high molecular weight. It is not excreted in breast milk.

T_1/2 from plasma is 30-60 minutes.

Indications

Prevention and therapy: deep vein thrombosis, pulmonary embolism (including in diseases of peripheral veins), coronary artery thrombosis, thrombophlebitis, unstable angina, acute myocardial infarction, atrial fibrillation (including accompanied by embolism), DIC syndrome, prevention and therapy of microthrombosis and microcirculation disorders, renal vein thrombosis, hemolytic-uremic syndrome, mitral heart disease (prevention of thrombosis), bacterial endocarditis, glomerulonephritis, lupus nephritis.

Prevention of blood coagulation during operations using extracorporeal circulation methods, during hemodialysis, hemoperfusion, peritoneal dialysis, cytapheresis, forced diuresis, when flushing venous catheters.

Preparation of non-coagulating blood samples for laboratory purposes and blood transfusion.

ICD codes

Dosage Regimen

Determine the dosage individually based on the route of administration, indication, clinical situation, and patient’s coagulation parameters.

For deep vein thrombosis and pulmonary embolism, administer an initial intravenous bolus of 5000 IU, followed by continuous IV infusion of 15-20 IU/kg/hour or 400 IU/kg/24 hours.

Alternatively, use subcutaneous administration: initial dose of 333 IU/kg, then 250 IU/kg every 12 hours.

For unstable angina and acute myocardial infarction, administer a bolus of 60-70 IU/kg (maximum 5000 IU), followed by infusion of 12-15 IU/kg/hour (maximum 1000 IU/hour).

Adjust the infusion rate to maintain the activated partial thromboplastin time (APTT) at 1.5-2.5 times the control value.

For thromboprophylaxis in moderate-risk surgery, administer 5000 IU subcutaneously 2 hours before surgery, then every 8-12 hours postoperatively.

In high-risk surgery, use 5000 IU subcutaneously 2 hours preoperatively, then 5000 IU every 8 hours postoperatively.

For extracorporeal circulation during cardiovascular surgery, use an initial dose of 300 IU/kg, with additional doses to maintain an activated clotting time (ACT) over 400 seconds.

For hemodialysis, administer an initial IV dose of 25-30 IU/kg, followed by an infusion of 1500-2000 IU/hour into the arterial line of the dialyzer.

To maintain venous catheter patency, instill a solution of 10-100 IU/ml into the catheter.

For pediatric patients, use 75 IU/kg as a bolus over 10 minutes, followed by 28 IU/kg/hour for infants under 1 year, or 20 IU/kg/hour for children over 1 year.

Adjust all doses based on frequent coagulation monitoring.

Do not administer intramuscularly due to the high risk of hematoma formation.

Adverse Reactions

From the blood coagulation system: possible gastrointestinal and urinary tract bleeding, bleeding at the injection site, in areas subjected to pressure, from surgical wounds, as well as hemorrhages in other organs, hematuria, thrombocytopenia.

From the digestive system: nausea, decreased appetite, vomiting, diarrhea, increased activity of liver transaminases.

Allergic reactions: skin hyperemia, drug fever, urticaria, rhinitis, skin itching and sensation of heat in the soles, bronchospasm, collapse, anaphylactic shock.

From the blood coagulation system: thrombocytopenia (can be severe up to fatal outcome) with subsequent development of skin necrosis, arterial thrombosis, accompanied by the development of gangrene, myocardial infarction, stroke.

From the musculoskeletal system: with prolonged use – osteoporosis, spontaneous fractures, calcification of soft tissues.

Local reactions: irritation, pain, hyperemia, hematoma, and ulcerations at the injection site.

Other: transient alopecia, hypoaldosteronism.

Contraindications

Bleeding, diseases accompanied by impaired blood coagulation processes, suspected intracranial hemorrhage, cerebral vascular aneurysm, hemorrhagic stroke, dissecting aortic aneurysm, antiphospholipid syndrome, malignant arterial hypertension, subacute bacterial endocarditis, erosive-ulcerative lesions of the gastrointestinal tract, severe parenchymal liver lesions, liver cirrhosis with esophageal varices, malignant neoplasms in the liver, shock conditions, recently performed surgical interventions on the eyes, brain, prostate, liver and biliary tract, condition after spinal puncture, menstruation, threatened miscarriage, childbirth (including recent), hypersensitivity to heparin.

Use in Pregnancy and Lactation

Use during pregnancy is possible only for strict indications, under careful medical supervision.

Contraindication: threatened miscarriage, childbirth (including recent).

Use during breastfeeding is possible for indications.

Use in Hepatic Impairment

Contraindications: severe parenchymal liver lesions, liver cirrhosis with esophageal varices, malignant neoplasms in the liver.

Use in Renal Impairment

Used for indications in patients with severe kidney diseases.

Pediatric Use

Use in children is possible for indications.

Geriatric Use

Use with caution in elderly patients (over 60 years, especially women).

Special Precautions

Use with caution in patients suffering from polyvalent allergy (including bronchial asthma), with arterial hypertension, dental manipulations, diabetes mellitus, endocarditis, pericarditis, in the presence of an intrauterine contraceptive device, with active tuberculosis, radiation therapy, hepatic insufficiency, chronic renal insufficiency, in elderly patients (over 60 years, especially women).

Intramuscular administration of heparin is not recommended due to the possibility of hematoma development, as well as intramuscular administration of other drugs during heparin therapy.

Use with caution externally for bleeding and conditions of increased bleeding tendency, thrombocytopenia.

During heparin treatment, monitoring of blood coagulation parameters is necessary.

Only physiological saline should be used to dilute heparin.

If severe thrombocytopenia develops (a decrease in platelet count by 2 times from the initial number or below 100,000/µl), it is necessary to urgently discontinue heparin use.

The risk of bleeding can be minimized by careful assessment of contraindications, regular laboratory monitoring of blood coagulation, and adequate dosing.

Drug Interactions

The anticoagulant effect of heparin is enhanced with simultaneous use of anticoagulants, antiplatelet agents, and NSAIDs.

Ergot alkaloids, thyroxine, tetracycline, antihistamines, as well as nicotine reduce the effect of heparin.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.