Streptokinase

Pharmacological properties of the drug Streptokinase

Streptokinase is a highly purified enzyme obtained by cultivating a strain of β-hemolytic streptococcus group C. It has fibrinolytic activity. When combined with plasminogen, streptokinase forms a complex that activates the transition of plasminogen in the blood or blood clot to plasmin. Plasmin dissolves fibrin clots and also leads to the degradation of fibrinogen and other plasma proteins. After the end of the infusion, the hyperfibrinolytic effect of streptokinase is observed only for a few hours, but the prolongation of thrombin time can persist for up to 24 hours due to a simultaneous decrease in fibrinogen levels and an increase in the number of circulating fibrin and fibrinogen degradation products. The half-life of the streptokinase-plasminogen complex, which activates plasmin, is about 23 minutes. Since streptokinase is a weak streptococcal antigen, it is partially inactivated by antistreptococcal antibodies, which are always present in the blood. The state of fibrinolysis is achieved only with the introduction of an excess amount of streptokinase necessary to neutralize the antibodies and the subsequent penetration of active streptokinase into the thrombus. The metabolites and mechanism of excretion of streptokinase are not known.

Indications for use

• acute myocardial infarction (up to 24 hours);
• thromboembolism of the pulmonary artery and its branches;
• thrombosis and thromboembolism of arteries: obliteration of arteriovenous shunt, chronic obliterating endarteritis, chronic, acute or subacute thrombosis of peripheral arteries;
• occlusion of the central vessels of the retina with a duration of less than 6-8 hours (arteries), less than 10 days (veins);
• arterial thrombosis;
• diagnostic or therapeutic procedures in children (after they have been carried out);
• vascular thrombosis during catheterization in newborns;
• thrombosis of the veins of internal organs, arteries and deep veins of the extremities (with a duration of less than 14 days) and the pelvis;
• rethrombosis after vascular surgery;
• hemodialysis shunt thrombosis;
• thrombosis during heart valve replacement;
• flushing intravenous catheters (including for hemodialysis);
• angina at rest in acute myocardial infarction (as monotherapy or as part of combination treatment).

Use of the drug Streptokinase

In case of myocardial infarction, a dose of 1,500,000 IU is prescribed intravenously, diluted in 100 ml of 0.9% sodium chloride solution or 5% glucose solution. Intracoronary administration is possible at a dose of 250,000–300,000 IU over 30–60 minutes. For deep vein thrombosis, pulmonary embolism and arterial occlusion - intravenous drip at a dose of 250,000 IU in 100-300 ml of solvent for 30 minutes. Immediately after administration of the loading dose, maintenance therapy begins. It is possible to administer 100,000 IU of streptokinase every hour for 3 days. A 12-hour infusion of 1,200,000 IU in 500 ml of solvent can be performed. It is very important that the infusion rate is constant. It is advisable to conduct a control study of vascular patency at the end of the infusion. If no positive clinical effect is observed within 3 days, therapy should be discontinued. If necessary, treatment with streptokinase can be extended for another 1–3 days. To dissolve blood clots in hemodialysis shunts, 100,000 IU of streptokinase is diluted in 100 ml of isotonic sodium chloride solution. 10,000–25,000 IU (10–25 ml) is injected into the thrombosed section of the shunt, after which its venous end is closed with a clamp. A sterile syringe tube is attached to the arterial end of the shunt to form an air cavity that provides pulsation of the artery. If necessary, the administration of streptokinase can be repeated after 30–45 minutes.

Release form and composition

Streptokinase is produced in the form of a lyophilisate for the preparation of a solution for intravenous and intra-arterial administration: white with a yellowish tint, porous, hygroscopic mass, compacted into a tablet (750,000 or 1,500,000 international units (IU) in bottles; 1 bottle in a cardboard box).

1 bottle of lyophilisate contains:

• active ingredient: streptokinase – 750,000 or 1,500,000 ME;
• auxiliary components: sodium L-glutamate, polygelin.

Contraindications to the use of the drug Streptokinase

• surgery, trauma, biopsy, puncture of a non-collapsing vessel (subclavian or jugular vein), cardiac tamponade, endotracheal intubation undergone in the previous 10 days;
• damage to the arteries of the brain, which can occur with severe hypertension (arterial hypertension), hypertensive or diabetic retinopathy, recent (up to 2 months) stroke or other cerebrovascular pathology;
• bleeding or a high risk of bleeding (hemorrhagic diathesis, thrombocytopenia, severe renal and/or liver failure, erosive and ulcerative lesions of the digestive tract in the previous 6 months - peptic ulcer, ulcerative colitis, diverticulitis, heavy menstrual bleeding, pregnancy - especially the first 18 weeks, condition after childbirth, active form of tuberculosis, tumors);
• risk of cardiac embolism, for example with atrial fibrillation due to mitral valve damage and bacterial endocarditis;
• recent treatment with streptokinase (from 5 days to 6 months before the previous detection of a high titer of neutralizing antibodies).

Directions for use and dosage

The solution prepared from the lyophilisate is administered intravenously (preferably into the vessels of the upper extremities), intraarterially, intracoronarily.

After intravenous administration of the drug, a pressure bandage is applied for 30 minutes, then monitoring the patient’s condition is required, since bleeding may develop (do not administer for 10 days after intramuscular injections and arterial punctures).

Before use, the lyophilisate is carefully (avoiding foaming) mixed with 5 ml of 0.9% Ringer's solution, sodium chloride or water for injection.

Streptokinase is used in the following doses:

• thrombosis of peripheral arteries or veins (for short-term lysis): intravenous drip of 1,500,000 IU of the drug hourly for 6 hours; the maximum dose per cycle is 9,000,000 IU. Repeated administration of Streptokinase for 6 hours is allowed after 5 days (no more);
• long-term thrombolysis: 250,000 IU of the drug intravenously over half an hour, then in the form of an infusion lasting from 12 hours to 3-5 days (no more) 100,000 IU per 1 hour. It is allowed to continue treatment after a break (if necessary) and it is possible to replace the drug funds for another homologous thrombolytic;
• thrombosis of coronary vessels: 1,500,000 IU intravenously over 1 hour, then 1000 IU of heparin is administered per hour. The effectiveness of therapy is monitored by determining thrombin or partial thromboplastin time;
• thrombosis of peripheral vessels (for long-term lysis): 250,000 IU for half an hour; maintenance dose - 100,000 IU per 1 hour. After 6-8 hours from the start of lysis, the thrombin time increases by 2-4 times. It is important to control the fibrinogen content in plasma (it should not be lower than 1 g per 1 l). In cases where the thrombin time increases more than 4 times after a few hours, the maintenance dose of the drug is reduced by 2 times and used until the thrombin time stabilizes in the above interval;
• intracoronary thrombus (for lysis): intracoronary (via a catheter) 20,000 IU, then 2000-4000 IU per 1 min; total dose – 140,000 IU over 30-40 minutes, or 250,000-300,000 IU over ½-1 hour. Despite the fact that recanalization may develop faster, drug administration is not stopped earlier than after 1 hour;
• acute, subacute, chronic peripheral thrombosis and embolism: 1000-2000 IU at intervals of 3-5 minutes. The number of injections and their duration are determined depending on the depth and localization of the vessel occlusion, the maximum dose is 120,000 IU per 3 hours. Simultaneous angioplasty is allowed;
• local thrombolysis for peripheral arterial embolism, acute, subacute and chronic thrombosis: 1000-2000 IU intra-arterially at intervals of 3-5 minutes until the effect is achieved. Total dose – 120,000 IU (no more);
• deep vein thrombosis and pulmonary embolism: 250,000 IU intravenously over half an hour, then 100,000 IU per 1 hour for 24-72 hours in accordance with the disease.

For children, Streptokinase is administered intravenously by drip over 20-30 minutes, at a dose determined based on the calculation - 1000-10000 IU per 1 kg of body weight; then carry out a long-term infusion of 1000 IU of the drug per 1 kg of body weight per 1 hour. The administration is stopped when significant bleeding is observed at the injection site. Heparin is used to prevent rethrombosis. Duration of therapy – 5 days (no more).

If the patency of the cannula is impaired, 100,000-250,000 IU of the drug, diluted in 2 ml of sodium chloride solution, is slowly injected into each blocked end. The duration of the procedure is 2 hours with further suction of the contents from the cannula.

Side effects

• blood and lymphatic system: often - bruises, bleeding at the injection site, nasal, urogenital or gastrointestinal bleeding; infrequently - hemorrhages in the joints, retina, brain with subsequent complications and possible death, hemorrhages in the liver, retroperitoneal bleeding, severe bleeding (fatal), rupture of the spleen; very rarely - bleeding into the pericardium, including myocardial perforation, during thrombolytic therapy for acute myocardial infarction;
• immune system: very often - the appearance of antibodies to streptokinase; often - allergic anaphylactic reactions (for example, itching, urticaria, rash, redness, shortness of breath, hypotension, bronchospasm, Quincke's edema); very rarely - delayed allergic reactions (for example, neuroallergic symptoms, nephritis, vasculitis, arthritis, serum reaction), severe allergic reactions, up to shock (including respiratory arrest);
• nervous system: rarely - neurological symptoms (for example, confusion, dizziness, agitation, hemiparesis, convulsions, paralysis) associated with cardiovascular disease or cerebral hemorrhage, with cerebral hypoperfusion;
• ophthalmological disorders: very rare: iridocyclitis/uveitis/iritis;
• cardiovascular system: often, at the beginning of treatment - bradycardia, tachycardia, hypotension; very rarely - cholesterol embolism;
• respiratory diseases: very rarely - cardiogenic pulmonary edema after intracoronary thrombolysis (in patients with extensive myocardial infarction);
• gastrointestinal tract: often - nausea, diarrhea, vomiting, pain in the epigastric region;
• general disorders and local reactions: often - headache, malaise, asthenia, chills, fever, muscle or back pain;
• laboratory parameters: often - increased levels of bilirubin and serum transaminases.

special instructions

During the therapy period, it is necessary to periodically monitor blood clotting (with an interval of 4 hours): thrombin or partial thromboplastin time - increasing the thrombin time by 2-4 times and the partial thromboplastin time by 1.5-2.5 times helps to avoid vascular reocclusion (with Taking this into account, appropriate doses of heparin are administered - 500-1000 IU per 1 hour, and then oral coumarin derivatives).

Before administering Streptokinase, children and patients with a history of elevated titers of antistreptokinase antibodies must undergo a sensitivity test to streptokinase.

In newborns, ultrasound examination of the skull is recommended. At the beginning of therapy, the infusion is carried out at a low rate; for the purpose of prophylaxis, 10 minutes before administration of the drug, it is possible to administer 100-200 mg of methylprednisolone and antihistamines. Repeated use of streptokinase increases the risk of allergic reactions.

To avoid the development of menorrhagia, patients with deep vein thrombosis should not interrupt their use of contraceptives during treatment.

After 5 days of therapy and within 1 year after its completion, with a previous streptococcal infection, there is a high probability of developing resistance due to the appearance of a high titer of antistreptococcal antibodies.

In cases where thrombolytic treatment is necessary, the use of other fibrinolytics (urokinase, etc.) is allowed.