Streptokinase
(lyophilizated powder for preparation of solution for injection 750000 Units and и 1500000 Units in phials)
Fibrokinase
International nonproprietary name
Streptokinase.
Pharmacotherapy group
Fibrinolytics.
Composition
1 vial contains 750000 and1500000 IU.
Pharmacological action
Pharmacodynamics
Streptokinase is an enzyme agent received from the culture of b-hemolytic streptococcus of C group. The preparation has a fibrinolytic activity that is conditioned by its capability to interact with blood plasminogen. The complex of streptokinase has a proteolytic activity and is catalyzes the transformation of plasminogen into plasmin. †Plasmin is capable to induce fibrin lysis in blood clots, inactivate fibrinogen, as well as factors V and VII of blood coagulation. The activity of streptokinase is determined by the activity of the preparation to lyse fibrin slot in certain conditions that is formed by the mixture of fibrinogen and thrombin solutions and is expressed in international units (IU).
Streptokinase is used for regeneration of thrombosed blood vessels conductivity; the preparation induces the thrombolysis affecting them not only from the surface but also penetrating inside the thrombuses (especially on fresh thrombuses).
Pharmacokinetics
The half-period after intravenous administration of 1500000 IU of streptokinase is an hour, the complex of streptokinase-plasminogen is about 23 minutes. It is biologically transformed in the liver by hydrolysis. It is excreted in small quantities by the kidney. On liver diseases the clearance is slowed down, the kidney impairment does not affect the clearance.
Indication
The indication of streptokinase is embolism of pulmonary artery and its branches, thrombosis and embolism of peripheral arteries, thrombosis of superficial and deep veins (extremities, pelvis), acute myocardial infarction (during first 12 hours), thrombosis of nervous tunic of eyeball and other conditions with acute embolism and thrombosis or with a risk of thrombosis formation.
Route of administration and dosage
Streptokinase is administered intravenously drop-by-drop and, if required, intra-arterially.
The preparation is administered intravenously in the initial dose of 250000 IU in 50 ml of isotonic solution of sodium chloride during 30 minutes (30 drops per minute). This dose usually induces the beginning of thrombosis lysis. After that the administration of streptokinase in the dose of 100000 IU per hour follows. The general duration of administration is, as a rule, 16Ч18 hours. The further treatment is carried out with heparin and anticoagulants of indirect action.
ѕри обширных артериальных и венозных тромбозах иногда необходимо длительное введение препарата.
Intra-arterial administration of streptokinase is used in the acute period of myocardial infarction (initial dose is 20000 IU; maintaining dose is 2000Ч4000 IU per minute during 30Ч90 minutes).
In all cases the administration of streptokinase shall be started the earliest possible as the best effect is achieved with fresh thrombuses.
The treatment with streptokinase is carried out under control of thrombin time and fibrinogen content in blood.
Specialindications
It is not recommended systemic use on myocardial infarction over 24 hours and more, on thrombosis of deep veins Ц 14 days and more, on thrombosis of retina vessels: arterial occlusions Ч 6Ч8 hours and more, venous ones Ч 10 days and more, on chronic arterial occlusions, comprising obliterating endarteritis Ц 6 weeks and more.
Side effects
On administration of streptokinase non-specific reactions to protein may develop, among them, headache, nausea, fever, allergic reactions (on marked allergic reactions corticosteroids shall be prescribed).
On a rapid intravenous administration the development of hypotension, cardiac rhythm disturbances may develop. The development of embolism shall be taken into account (due to thrombus elements mobilization).
Contraindications
The preparation is contraindicated on acute blood losses, hemorrhagic diathesis, fresh ulcers of the gastrointestinal tract, after the surgical operations that took place not long ago, on marked hypertension, septic endocarditis, cerebral circulation disturbances, pulmonary tuberculosis (cavernous forms), in the first trimester of pregnancy.
Precautions
The treatment is carried out under monitoring of the parameters of thrombin and partial thromboplastin time. Special care shall be taken on marked impairment of liver and kidney function, insulin diabetes, bronchial asthma, underwent streptococcosis infection, comprising rheumatism, bronchiectasis with hemoptysis, esophageal veins dilatation, recent prescription of anticoagulants, conditions after cardiopulmonary resuscitation, artificial pulmonary ventilation, bleeding on urological diseases, comprising urolithiasis, as well as on chronic diseases of gastrointestinal tract, menorrhagia, menstruation, on earlier course (from 5 to 1 year) of treatment with streptokinase, in the elderly age (older than 75 years).
The preparation is used in the in-patient department.
Interaction with other medications
Heparin, derivatives of coumarin, dipiridamol, NSAID, comprising acetylsalicylic acid, dextrans, valproic acid increase the anticoagulative effect and increase risk of bleeding. †It is not compatible with plasma-substituting solutions Ц hydroxyethylated starch and dextran.
Overdosing
Symptoms: increasing of side effects (more often -- hemorrhage)
Treatment: termination of hemorrhage (if possible), prescription of antifibrinolytic preparations (tranexamic acid, p-amino-benzoic acid, kallikrein and protease inhibitors, comprising aprotinin, aminocapronic acid Ц 5 g/hour, then 1 g/hour during 4Ч8 hours to achieve the desired effect), blood loss substitution (besides dextran and hydroxyethylated starch), symptomatic treatment.
Product form
Powder for preparation of the solution for injections. Vials of 750000 and 1500000 IU.
