Thromboflux (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Bharat Serums & Vaccines, Ltd. (India)

ATC Code

B01AD01 (Streptokinase)

Active Substance

Streptokinase (Rec.INN registered by WHO)

Dosage Form

Thromboflux

Lyophilisate for the preparation of solution for intravenous and intra-arterial administration 1.5 million IU: vial 1 pc.

Dosage Form, Packaging, and Composition

1,500,000 IU – vials (1) – cardboard packs.

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. When combined 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 fibers in blood clots and thrombi, causing the 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. It reduces the frequency of fatal outcomes in myocardial infarction. It improves heart functional parameters. It 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, the prolongation of thrombin time persists for up to 24 hours due to the simultaneous decrease in fibrinogen and the 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 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 a duration of 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 internal organ veins, thrombosis of deep veins of the extremities (duration less than 14 days) and pelvis. Re-thrombosis after vascular surgery. Hemodialysis shunt thrombosis. Thrombosis during 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 intracoronarily. The dose, route, and duration of therapy are determined individually based on the clinical indication.

For acute myocardial infarction, administer 1,500,000 IU as an intravenous infusion over 60 minutes. Initiate therapy within 24 hours of symptom onset.

For pulmonary embolism or deep vein thrombosis, administer a loading dose of 250,000 IU via intravenous infusion over 30 minutes. Follow with a maintenance dose of 100,000 IU per hour for 24 to 72 hours, depending on clinical response.

For arterial thrombosis or embolism, administer via intra-arterial infusion. A typical regimen is 5,000 to 10,000 IU per minute for up to 6 hours. Continue until lysis is confirmed or the maximum dose is reached.

For occlusion of central retinal vessels, administer 500,000 IU intravenously. Initiate treatment within 6-8 hours for arterial occlusion and within 10 days for venous occlusion.

For catheter occlusion, instill 250,000 IU in 2 mL of solution into the catheter. Clamp for 2 hours, then aspirate and flush with saline.

Reconstitute the 1,500,000 IU vial with 5-10 mL of Sodium Chloride Injection (0.9%). Gently swirl or roll the vial to dissolve; do not shake. Further dilute the reconstituted solution in 50-500 mL of Sodium Chloride Injection (0.9%) for infusion.

Monitor blood coagulation parameters every 4 hours during infusion. Adjust heparin therapy to maintain thrombin time at 2-4 times the normal control value.

Prior to administration in children or patients with recent streptococcal infection, perform a sensitivity test for antistreptokinase antibodies.

Premedicate with an antihistamine and 100-200 mg of methylprednisolone 10 minutes before infusion to reduce the risk of allergic reactions.

Do not administer concomitantly with hydroxyethyl starch or dextran plasma substitutes.

Avoid intramuscular injections and arterial punctures for 10 days following treatment. Apply a pressure bandage to all intravenous access sites for at least 30 minutes after catheter removal.

Adverse Reactions

From the blood coagulation system: bleeding from injection sites, gums; hemorrhages into the skin, into the peri- and myocardium, into the 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 its fragmentation), including pulmonary artery (with deep vein thrombosis), distal parts of the artery (cholesterol embolus with 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 multiple administrations – 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 and ulcerative lesions of the gastrointestinal tract, inflammatory diseases of the colon, recent multiple injuries, aneurysm, tumors with a tendency to bleed, 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; permanent bladder 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 it is necessary to use during lactation, 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

It is possible to use in children 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 or partial thromboplastin time (avoiding vascular reocclusion is allowed by increasing thrombin time by 2-4 times, and partial thromboplastin time by 1.5-2.5 times; taking this into account, it is necessary to administer an appropriate amount of heparin – 0.5-1 thousand IU/hour, 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 should be performed.

In newborns, ultrasound of the skull 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, for prophylactic purposes, the administration of antihistamines and 100-200 mg of methylprednisolone is possible.

Repeated administration of streptokinase may lead to an increased 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 it is necessary to carry out thrombolytic therapy 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.