Streptokinase

Pharmacological properties

streptokinase-biopharma is a highly purified enzyme obtained from a cultured strain of β-hemolytic streptococcus group C. is a protein with a molecular weight of about 50,000 da. exhibits fibrinolytic activity. with plasminogen, streptokinase forms a complex that activates the transition of plasminogen (blood or blood clot) to plasmin. plasmin, which exhibits proteolytic enzymatic activity, causes lysis of fibrin filaments of blood clots, degradation of fibrinogen and other plasma proteins, including v (accelerin) and vii (convertin) coagulation factors. dissolves blood clots, acting both on their surface and from the inside. streptokinase is most effective for fresh fibrin clots (before retraction), restores patency of thrombosed blood vessels. after the end of the infusion, the fibrinolytic effect of streptokinase reaches a maximum after 45 minutes and lasts for several hours. however, the extension of thrombin time can persist for up to 24 hours as a result of a simultaneous decrease in the level of fibrinogen and an increase in the number of circulating degradation products of fibrin and fibrinogen.

Pharmacokinetics T_½ the streptokinase-plasminogen complex is about 23 minutes. Since streptokinase is a weak streptococcal antigen, it is partially inactivated by anti-streptococcal antibodies, which are always present in the blood. Therefore, fibrinolysis is achieved only with the introduction of an excessive amount of streptokinase necessary to neutralize antibodies and further penetration of active streptokinase into the thrombus. Most of the streptokinase breaks down to peptides and is excreted by the kidneys.

Indications

• Acute coronary syndrome with a stable rise in the st segment or recent blockade of the left leg of the atrioventricular bundle, acute myocardial infarction with q wave - no later than 12 hours after the onset of the disease (if the drug is used after the above period, the treatment result cannot be predicted); massive deep vein thrombosis with a risk of gangrene; pulmonary embolism; acute, subacute and chronic thrombosis of peripheral arteries with the threat of ischemia; thrombosis of the central artery or central retinal vein.

Application

The drug streptokinase-biopharma, bottles of 750,000 IU, are prescribed iv or iv. the drug streptokinase-biopharma, bottles of 1,500,000 IU, are prescribed iv or intracoronary.

Cooking solution. At the beginning of therapy, a concentrated solution of Streptokinase-Biopharma is prepared: slowly add 5 ml of sterile 0.9% NaCl solution (sodium chloride) into the vial and mix gently by rotating the vial. Do not add any other medicines to the vial. To prepare an infusion solution, add the required amount of concentrated solution to 50-200 ml of sterile 0.9% sodium chloride solution, or Ringers solution, or 5% glucose solution.

Dosage of the drug Streptokinase-Biopharma

Acute myocardial infarction with ST segment elevation. The dose is 1.5 million IU iv for 1 hour.

The introduction of the drug intracoronary is carried out according to the scheme: 20,000 IU Streptokinase-Biopharm bolus; in the future, supportive fibrinolytic therapy is carried out with iv administration of the drug at a dose of 2000-4000 IU / min for 0.5-1.5 hours (depending on the speed of restoration of patency of the coronary artery). After completion of Streptokinase-Biopharm administration, acetylsalicylic acid (150 mg / day, per os) is recommended.

Deep vein thrombosis. The initial dose is 250,000 IU, which is administered iv for 0.5 h, then a maintenance dose of 100,000 IU / h is administered. The duration of treatment is 72 hours.

Pulmonary embolism. In case of short-term thrombolysis, Streptokinase-Biopharma drug is administered iv 1,500,000 IU for 1-2 hours.

The standard mode of administration: an initial dose of 250,000 IU, which is administered for 0.5 h; maintenance dose - 100,000 IU / h. The duration of treatment is 24 hours.

Peripheral artery thrombosis. Streptokinase-Biopharm is used intravenously through a local intra-arterial catheter according to the following scheme: phased infusion - 1000–2500 IU with an interval of 3-5 minutes, maximum duration of administration - 10 hours. Total maximum dose - 250,000 IU.

In the presence of multiple occlusions, the initial dose of Streptokinase-Biopharm is 250,000 IU, which is administered for 0.5 h, then the maintenance dose of 100,000 IU / h is continued. The duration of treatment is up to 5 days.

Thrombosis of the central vessels of the retina. The initial dose is 250,000 IU, which is administered for 0.5 hours. Subsequently, a maintenance dose of 100,000 IU / h is administered. The duration of treatment is 12 hours.

Treatment control

In the treatment with streptokinase, the level of plasminogen and fibrinolysin in the blood plasma decreases and the level of degradation products increases, which is confirmation of the fibrinolytic activity of the drug. Therefore, treatment control is carried out by determining thrombin time (TB) or activated partial thromboplastin time (APTT). If 4 hours after the start of treatment with Streptokinase-Biopharma TV or APTT does not increase by more than 1.5 times compared to the level at the beginning of treatment, it is recommended to stop administration due to the presence of streptokinase resistance.

Further treatment. After drug therapy, further treatment with anticoagulants or antiplatelet agents is necessary to prevent recurrence of thrombosis. The possible risk of bleeding during heparin therapy should be considered.

Contraindications

Hypersensitivity to the drug.

Due to the increased risk of bleeding due to thrombolytic therapy, the drug should not be used in the following situations:

• the presence at this time or recent bleeding; surgery carried out in the previous 10 days (including implantation of vascular prostheses), trauma (especially the head), biopsy, puncture of a vessel that does not subside (subclavian or jugular vein), spinal puncture, cardiac tamponade, endotracheal intubation;
• damage to the arteries of the brain, which is possible with severe hypertension, hypertensive or diabetic retinopathy, a recent stroke (up to 2 months) or other cerebrovascular pathology, aneurysms;
• bleeding or a high risk of bleeding (hemorrhagic diathesis, thrombocytopenia);
• severe renal and / or liver failure;
• erosive and ulcerative lesions of the gastrointestinal tract in the previous 6 months - peptic ulcer, ulcerative colitis, diverticulitis;
• menstrual bleeding;
• condition after childbirth;
• active form of tuberculosis;
• tumors;
• acute pancreatitis;
• recent treatment with streptokinase (from 5 days to 6 months, with a preliminary determination of a high titer of neutralizing antibodies);
• uncontrolled hypertension with systolic blood pressure of 200 mm RT. Art. and / or diastolic blood pressure of 100 mm RT. st .;
• concomitant use of oral anticoagulants (international normalized ratio of 1.3);
• mitral heart defects with atrial fibrillation, septic endocarditis or pericarditis.

Side effects

Common disorders: headache, muscle pain, back pain, asthenia, chills and fever, malaise.

On the part of the blood system: often - hemorrhages (bleeding) at the injection site, gastrointestinal, genitourinary, nosebleeds; infrequently - complicated cerebral hemorrhage with a possible fatal outcome, hepatic hemorrhage, rupture of the spleen, retroperitoneal bleeding, hemorrhage in the joints, retina; very rarely - pericardial hemorrhage in patients with acute myocardial infarction, myocardial ruptures.

In severe hemorrhagic complications, streptokinase therapy is discontinued and proteinase inhibitors, for example aprotinin, are prescribed (first from 500,000 to 1 million IU, after which 50,000 IU are administered iv hourly drip until the bleeding stops). Combinations with synthetic antifibrinolytics are recommended. If necessary, coagulation factors are prescribed.

On the part of the immune system: very often - an increase in the level of antibodies to streptokinase; often - allergic anaphylactic reactions (rash, including in the form of vesicles, redness of the face and skin, itching, urticaria, angioedema, dyspnea, bronchospasm); very rarely - arthritis, vasculitis, back pain, nephritis and neuroallergic syndrome (polyneuropathies - Guillain-Barré syndrome, serum polyneuropathy), serum sickness, which coincided with the appointment of streptokinase.

If an allergic reaction or anaphylactic shock occurs, the drug should be discontinued immediately (interrupt the infusion) and appropriate treatment should be prescribed (in severe cases, anti-shock therapy: adrenaline; high doses of corticosteroids; infusion therapy, oxygen therapy). After which treatment can be continued with homologous fibrinolytics.

From the nervous system: rarely - neurological symptoms (dizziness, confusion, paralysis, hemiparalysis, agitation, convulsions) as a manifestation of cerebral hemorrhage or cardiovascular disorder with brain hypoperfusion.

From the side of the organ of vision: very rarely - iritis, uveitis, iridocyclitis.

From the cardiovascular system: often at the beginning of therapy - arterial hypotension, tachycardia, bradycardia; very rarely - cholesterol embolism, extrasystole, heart pain.

In patients with myocardial infarction, reactions were noted that were regarded as a complication of myocardial infarction: very often - hypotension, tachycardia, arrhythmia, angina pectoris; often - angina that does not stop, heart failure, recurrent myocardial infarction, cardiogenic shock, pericarditis, pulmonary edema; infrequently - cardiac arrest, mitral valve insufficiency, pericardial hemorrhage, cardiac tamponade, myocardial rupture, pulmonary or peripheral embolism. These cardiovascular complications can be life threatening and lead to death. The possibility of peripheral embolization is not excluded during local lysis in the arteries.

From the respiratory system: very rarely - non-cardiogenic pulmonary edema after intracoronary thrombolytic therapy in patients with advanced myocardial infarction; shortness of breath, bronchospasm.

From the digestive tract: often - nausea, diarrhea, epigastric pain, vomiting.

Laboratory indicators: often - a transient increase in transaminases and bilirubin.

special instructions

The drug is used in a hospital, as well as at the prehospital stage by a doctor of a specialized emergency medical team with mandatory subsequent hospitalization of the patient in a specialized department of the hospital.

To determine the sensitivity to the components of the drug, it is recommended to conduct a skin test (100 IU Streptokinase-Biopharma). With a positive reaction, homologous fibrinolytics should be used. In case of a negative reaction - after 15–20 min, the drug can be administered in a therapeutic dose.

The use of Streptokinase-Biopharm should be started as early as possible, since the best effect is noted with fresh blood clots. Before the introduction of the drug, it is recommended to determine the content of fibrinogen, TV and APTT.

The treatment is carried out under the control of TV and the level of fibrinogen in the blood.

Special care should be taken when using streptokinase in patients over the age of 75 years.

During and after Streptokinase-Biofaram therapy, invasive procedures, including injections, should be avoided, this may increase the risk of bleeding. If there is a need for puncture of the artery, preference should be given to the vessels of the upper extremities. After the puncture, the puncture site should be pressed for at least 30 minutes and this site should be examined to identify the first signs of bleeding.

Since antibodies to streptokinase are possible 5 days after the start of use, this can lead to the development of resistance or hypersensitivity reactions. Therefore, the drug should not be used for more than 5 days. Repeated administration is possible no earlier than 12 months after the start of therapy. The effectiveness of the drug may decrease in patients who have recently had a streptococcal infection (streptococcal pharyngitis, acute rheumatic fever, glomerulonephritis). In order to prevent the development of adverse reactions, it is necessary to start the infusion of the drug very slowly, observing the patients condition. To reduce the likelihood of allergic reactions, corticosteroids can be prescribed before streptokinase is administered.

If the patient received heparin immediately before treatment with streptokinase, its effect is neutralized by the introduction of protamine sulfate. With previous treatment with indirect anticoagulants, vitamin K preparations are recommended.

The use of heparin can begin no earlier than 4 hours after the cessation of drug infusion.

Not recommended:

• systemic purpose: deep vein thrombosis - not later than 14 days later; myocardial infarction - not later than 12 hours; occlusion of the central vessels of the retina, arterial occlusion - not later than after 6-8 hours; venous occlusion - not later than 10 days later;
• local thrombolysis: myocardial infarction - no later than 12 hours; embolism - not later than after 6 weeks.

The drug Streptokinase-Biopharm is not used for washing a venous catheter.

Use during pregnancy and lactation. During pregnancy, the use of the drug is not recommended. If it is necessary to use the drug, breast-feeding should be discontinued.

Children. There is no experience with the use of the drug in children.

The ability to influence the reaction rate when driving vehicles or mechanisms. During treatment with the drug, it is not recommended to drive vehicles or mechanisms.

Interactions

With the simultaneous administration of streptokinase and drugs that affect the blood coagulation system (heparin, indirect anticoagulants, antiplatelet agents), the risk of bleeding increases.

Before starting a prolonged systemic thrombolysis, one should wait for a decrease in the severity of the effects of drugs acting on the formation and function of platelets.

Incompatibility. Streptokinase is incompatible with dextrans and hydroxylated starch.

Overdose

Symptoms: increased severity of side effects, most often bleeding. in case of bleeding, the administration of streptokinase should be discontinued.

If it is necessary to quickly restore the state of the blood coagulation system, treatment with aminocaproic acid preparations should be started. If necessary, the restoration of blood volume is recommended the introduction of plasma substitutes, red blood cells or whole blood, the appointment of antifibrinolytic agents (tranexamic acid, aprotinin).

Storage conditions

At a temperature of 2–8 ° c.