Heberkinase recombinant streptokinase (Lyophilisate) Instructions for Use

ATC Code

B01AD01 (Streptokinase)

Active Substance

Streptokinase (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Thrombolytic – tissue plasminogen activator

Pharmacotherapeutic Group

Fibrinolytic agent

Pharmacological Action

Fibrinolytic agent. It is a protein with a molecular weight of about 50,000 daltons, produced by certain strains of streptococcus. Upon binding with plasminogen, Streptokinase forms a complex that activates the conversion of blood plasminogen or blood clot plasminogen into plasmin (fibrinolysin) – a proteolytic enzyme that dissolves fibrin strands in blood clots and thrombi, causing degradation of fibrinogen and plasma proteins, including clotting factors V and VII.

Since Streptokinase is a weak streptococcal antigen, its intravenous administration may be neutralized by circulating antibodies; therefore, the state of fibrinolysis is achieved by administering an excess amount of streptokinase necessary to neutralize antibodies.

During intravenous infusion, it reduces blood pressure and total peripheral vascular resistance with a subsequent decrease in cardiac output; in patients with chronic heart failure, it improves left ventricular function. Reduces mortality in myocardial infarction. Improves heart functional parameters. Reduces the number of thrombotic complications in cardiovascular diseases and fatal outcomes from pulmonary embolism. The maximum effect is observed after 45 minutes. After the end of the infusion, the fibrinolytic effect is observed for several hours, prolongation of thrombin time persists for up to 24 hours due to the simultaneous decrease in fibrinogen and increase in the number of circulating fibrin and fibrinogen degradation products. It activates not only tissue fibrinolysis (action aimed at dissolving a thrombus – thrombolysis) but also systemic fibrinolysis (cleavage of blood fibrinogen), therefore bleeding may develop (due to hypofibrinogenemia). It is most effective against fresh fibrin clots (before retraction). With intracoronary administration, thrombolysis occurs after 1 hour.

Pharmacokinetics

The initial T_1/2 is 13-23 minutes, the terminal half-life is 83 minutes. Streptokinase is not metabolized.

Indications

Acute myocardial infarction (within up to 24 hours), pulmonary embolism and its branches. Thrombosis and thromboembolism of arteries (acute, subacute, chronic thrombosis of peripheral arteries, chronic obliterating endarteritis, obliteration of an arteriovenous shunt), occlusion of central retinal vessels with duration less than 6-8 hours (arteries), less than 10 days (veins); arterial thrombosis due to diagnostic or therapeutic procedures in children, vascular thrombosis during catheterization in newborns. Thrombosis of visceral veins, thrombosis of deep veins of the extremities (duration less than 14 days) and pelvis. Re-thrombosis after vascular surgery. Hemodialysis shunt thrombosis. Thrombosis with prosthetic heart valves. Washing of intravenous catheters (including for hemodialysis). Mono- or combination therapy for rest angina in acute myocardial infarction.

ICD codes

Dosage Regimen

Administer intravenously, intra-arterially, or intracoronary. Determine the dose, route, and duration of therapy individually based on the specific clinical indication and patient status.

For acute myocardial infarction, initiate therapy as soon as possible, preferably within 12 hours of symptom onset. Administer 1,500,000 IU as an intravenous infusion over 60 minutes.

For pulmonary embolism and deep vein thrombosis, administer a loading dose of 250,000 IU intravenously over 30 minutes, followed by a maintenance infusion of 100,000 IU/hour for 24-72 hours.

For arterial thrombosis or embolism, administer via intra-arterial infusion. A typical regimen is 100,000 IU/hour for a duration of 24 to 72 hours, guided by angiographic evidence of clot lysis.

For occlusion of central retinal vessels, administer intra-arterially. The recommended dose is 100,000 – 500,000 IU as a brief infusion. Initiate treatment within 6-8 hours for arterial occlusion and within 10 days for venous occlusion.

For catheter clearance, instill a solution containing 250,000 IU in 2 mL into the occluded catheter. Clamp the catheter for 2 hours, then aspirate the contents and flush thoroughly with 0.9% sodium chloride solution.

Reconstitute the lyophilisate strictly according to instructions using 0.9% Sodium Chloride Injection. Do not use other diluents. Administer the prepared solution immediately; do not store.

Monitor the patient closely for signs of bleeding during and after infusion. Perform coagulation parameter checks (e.g., thrombin time) at 4-hour intervals. Avoid intramuscular injections and non-essential vessel punctures.

Premedicate with an intravenous corticosteroid (e.g., 100-200 mg methylprednisolone) and an antihistamine 10 minutes prior to infusion to mitigate potential allergic or febrile reactions.

Adverse Reactions

From the blood coagulation system bleeding from injection sites, gums; hemorrhages into the skin, peri- and myocardium, brain, hematoma; internal bleeding (including from the gastrointestinal tract, urogenital, retroperitoneal).

From the cardiovascular system reperfusion arrhythmia, non-cardiogenic pulmonary edema (with intracoronary administration), thromboembolism (due to thrombus mobilization or fragmentation), including pulmonary artery (with deep vein thrombosis), distal artery sections (cholesterol embolus during local thrombolysis), embolic stroke; capillary toxicosis (Schönlein-Henoch syndrome); increased ESR.

Allergic reactions predominantly with repeated administrations – skin hyperemia, urticaria, generalized exanthema, dyspnea, bronchospasm, hyperthermia, chills, headache, myalgia, back pain, decreased blood pressure, brady- or tachycardia, arthritis, vasculitis (including hemorrhagic), nephritis, polyneuropathy, angioedema, anaphylactic shock.

From laboratory parameters with repeated administration – increased activity of hepatic transaminases and alkaline phosphatase, GGT and CPK; hyperbilirubinemia, decreased cholinesterase activity.

Other spleen rupture.

Contraindications

Hypersensitivity to streptokinase; bleeding, hemorrhagic diathesis, erosive-ulcerative lesions of the gastrointestinal tract, inflammatory bowel diseases, recent multiple injuries, aneurysm, tumors prone to bleeding, brain tumors or metastases to the CNS, arterial hypertension (BP more than 200/110 mm Hg), diabetic retinopathy, acute pancreatitis, endocarditis, pericarditis, mitral heart defects with atrial fibrillation, tuberculosis (active form), lung cavities, sepsis, septic thrombosis, postoperative period (8-12 postoperative days, 3-6 weeks after extensive surgical interventions, 8 weeks after neurosurgical operations), recent biopsy of internal organs, 4 weeks after translumbar arteriography, 3 months after acute hemorrhagic stroke; first 18 weeks of pregnancy; pregnancy pathology associated with an increased risk of bleeding, recent childbirth (within 10 days) or artificial termination of pregnancy; indwelling urinary catheter.

With caution: hepatic/renal failure, bronchial asthma, previous streptococcal infection (including rheumatism), bronchiectasis with hemoptysis, esophageal varices, recent prescription of anticoagulants, conditions after cardiopulmonary resuscitation (including indirect cardiac massage), mechanical ventilation, nephrourolithiasis, menorrhagia, menstrual period, prior treatment with streptokinase (from 5 days to 1 year), elderly age (over 75 years).

Use in Pregnancy and Lactation

Streptokinase is contraindicated for use during pregnancy (especially during the first 18 weeks of pregnancy, due to the possibility of premature placental abruption) and in the postpartum period.

If use during lactation is necessary, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency.

Use in Renal Impairment

Use with caution in renal insufficiency.

Pediatric Use

Use in children is possible according to indications in doses and regimens recommended according to age.

Geriatric Use

Use with caution in elderly patients (over 75 years).

Special Precautions

When using streptokinase, periodic (at 4-hour intervals) monitoring of blood coagulation is necessary: thrombin time or partial thromboplastin time (to avoid vascular reocclusion, an increase in thrombin time by 2-4 times and partial thromboplastin time by 1.5-2.5 times is allowed; taking this into account, it is necessary to administer an appropriate amount of heparin – 0.5-1 thousand IU/h, and then oral coumarin derivatives).

Before administration to children and patients with a history of high titer of antistreptokinase antibodies, a sensitivity test to streptokinase is performed.

In newborns, cranial ultrasound is recommended. At the beginning of treatment, the infusion should be carried out at a low rate; 10 minutes before the start of the infusion, prophylactic administration of antihistamines and 100-200 mg of methylprednisolone is possible.

Repeated administration of streptokinase may increase the likelihood of allergic reactions.

During treatment for deep vein thrombosis, female patients should not discontinue contraceptives to avoid the development of menorrhagia.

After 5 days of treatment and for 1 year after the end of therapy, after a streptococcal infection, there is a high probability of developing resistance due to the appearance of a high titer of antistreptococcal antibodies. If thrombolytic therapy is necessary in this case, other fibrinolytics (urokinase, etc.) can be used.

For intravenous administration, vessels of the upper extremities are preferable; after the procedure – apply a pressure bandage for 30 minutes, with subsequent monitoring, due to possible bleeding (do not administer for 10 days after arterial punctures and intramuscular injections).

Drug Interactions

With simultaneous use with heparin, coumarin derivatives, dipyridamole, dextrans, acetylsalicylic acid, the effect of streptokinase is potentiated.

The agent is incompatible with plasma-substituting drugs – hydroxyethyl starch or dextran.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°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.