Pharmakinaza

General characteristics. Structure:

International name: Streptokinasa; main physical and chemical properties: white powder or white hygroscopic weight; structure: 1 bottle contains Streptokinasas of 750 000 ME or 1500 000 ME Excipients: albumine human, полижелин.

Pharmacological properties:

Pharmacodynamics. High cleaning drug of Streptokinasa received from a filtrate of culture of beta and hemolitic streptococci of Lansfild of group C which promotes transformation of plasminogen into plasmin. Plasmin destroys fibrin clots, and also leads to degradation of fibrinogen and other proteins of a blood plasma. After intravenous or intra arterial administration and neutralization of an individual antiserum capacity to Streptokinasa, it begins to activate systemically or locally fibrinolitic processes. After drug infusion hyper fibrinolitic effect several hours, but thanks to decrease in level of fibrinogen and increase in quantity of products of degradation of fibrinogen and fibrin that occurs at the same time, an indicator of thrombin time can raise till 24 o'clock.

Pharmacokinetics. The complex elimination half-life Streptokinasa plasminogen activating plasmin makes about 23 min. This complex is partially inactivated by anti-streptococcal antibodies. The formed plasminogen, can be inactivated by the circulating inhibitors alpha 2 - plasmin and alpha 2 - macroglobulin. The most part of Streptokinasa breaks up to peptides and is allocated with kidneys.

Indications to use:

Acute myocardial infarction, deep vein thrombosis, embolism of a pulmonary artery, acute and subacute fibrinferments of peripheral arteries, fibrinferments of vessels of a retina.

Route of administration and doses:

It is appointed intravenously or vnutriarterialno after dissolution of contents of a bottle in normal saline solution or 5% glucose solution. System appointment. At treatment of an acute myocardial infarction by a short-term lysis, 1500000 ME PHARMAKINAZATM dissolve in 100 ml 0,9% of solution of sodium of chloride (or 5% of solution of glucose) and enter within 60 min. The adult with occlusion of peripheral venous and arterial vessels at a short-term thrombolysis enter initial dose ФАРМАКИНАЗАтм - 250000 MO, dissolved in 100-300 ml of 0,9% of solution of sodium of chloride (or 5% of solution of glucose) within 30 min., after that - a maintenance dose 1200000 ME on 500 ml of solvent each hour within 6 hours. Six-hour infusion of drug can be repeated for days depending on therapeutic effect. Repeated treatment under no circumstances should not be performed later, than in 5 days after the first course. Alternative short-term a lysis is the long thrombolysis at treatment of occlusions of peripheral vessels. The initial dose of drug ФАРМАКИНАЗАтм 250000 ME is entered within 30 min. then appoint a maintenance dose 100000 ME each hour. Duration of therapy depends on prevalence and localization of occlusion of a vessel. At occlusion of peripheral vessels the maximum duration of a course of treatment - 5 days. At fibrinferments of the central vessels of a retina a lysis of arterial occlusions has to last no more than 24 h, venous - no more 72nd hour. If at considerable occlusions continuation of a thrombolysis is shown, it is necessary to adhere to an interval between receptions (about one days) then to appoint another тромболитик (an urokinase, t-PA). Local thrombolysis. At an acute myocardial infarction appoint intra coronary bolyusny administration of drug ФАРМАКИНАЗАтм on average 20000 ME and a maintenance therapy in a dose from 2000 to 4000 ME in a minute within 30-90 min. To patients with acute, subacute and chronic peripheral fibrinferments and embolisms enter from 1000 to 2000 bucketed ME PHARMAKINAZATM from 3 to 5 min. Duration of use depends on prevalence of defeat and localization of occlusion of a vessel and is carried out till 3 o'clock by the general dose of at most 120000 ME PHARMAKINAZATM. If necessary transdermal transluminal angioplasty can be at the same time executed. Therapy control. System appointment. At a short-term lysis (during 6 h) appoint heparin in time or after infusion of drug ФАРМАКИНАЗАтм if levels of thrombin time or partial tromboplastinovy time respectively grew less, than two or by one and a half times from normal control amounts. Indicators of thrombin time and partial tromboplastinovy time have to raise respectively by 2-4 times and by 1,5-2,5 times that allows to provide enough retromboz. If infusion of drug ФАРМАКИНАЗАтм does not repeat, it is necessary to appoint therapy heparin along with peroral anticoagulants. Long a lysis is controlled on an indicator of thrombin time. Two - quadruple prolongation of an indicator of thrombin time in 6-8 hours from the beginning to a lysis is possible criterion of anticoagulating protection, in case of increase in an indicator of thrombin time it is more, than by 4 times, dose ФАРМАКИНАЗАтм it is necessary to reduce twice. Local thrombolysis. Efficiency of a local thrombolysis can be estimated according to an angiography. If more than 15 min. after carrying out a thrombolysis the sufficient blood stream remains, treatment is considered successful and it can be stopped (before performance of an angiography usually it is recommended to apply heparin to prevention of the thromboses induced by a catheter). Further treatment. After each course of therapy by Streptokinasa for the purpose of prevention of retromboz it is possible to appoint further treatment anticoagulants or inhibitors of aggregation of thrombocytes. During therapy by heparin it is necessary to pay special attention to the increased risk of emergence of hemorrhages. Therapy by heparin is controlled individually on indicators of thrombin time or partial tromboplastinovy time. The purpose of treatment is increase in duration of indicators of thrombin time by 2-4 times and tromboplastinovy - by 1,5-2,5 times. It is possible to apply peroral anticoagulants to long prevention, for example, derivatives of coumarin or inhibitors of aggregation of thrombocytes.

Features of use:

Drug can be used only in the conditions of a hospital! Success of therapy by Streptokinasa depends on time of the beginning of therapy after emergence of the first symptoms. It is not recommended:     

system appointment: a deep vein thrombosis - later, than in 14 days a myocardial infarction - later, than in 12 h; - occlusion of the central vessels of a retina, arterial vessels - later, than in 6-8 h, venous occlusions - later, than in 10 days    

 local thrombolysis: - A myocardial infarction - later, than in 12 h; embolisms - later, than in 6 weeks. In need of thrombolytic therapy and with high concentration of antibodies against Streptokinasa or at recent use of Streptokinasa (more than 5 days and less than a one years ago), it is recommended to apply homological fibrinolitik (for example, an urokinase or t-PA) Doses to children: still there is no sufficient experience of use of drug for children.

The individualized assessment of risk / advantage the Risk of emergence of hemorrhagic complications has to be compared with the expected advantages in the following cases: recently transferred heavy a bleeding GIT, extensive surgical interventions (from 6 to 10 days after operation of dependence on weight of surgical intervention), an injury or cardiopulmonary resuscitation, a biopsy of body, a puncture of vessels which do not give in to a compression intramuscular injections; intubation; recent childbirth, abortion; diseases of an urinogenital path with the existing or potential bleeding points (bladder catheterization); suspicion on a heavy atherosclerotic degeneration of vessels, cerebrovascular diseases, a heavy diabetes mellitus, a diabetic / hemorrhagic retinopathy; diseases of lungs with formation of cavities (for example, cavernous forms of tuberculosis) or heavy bronchitis;    serious illness of a liver or kidneys;    defects of the mitral valve or fibrillation of auricles; endocarditis or pericardis; separate cases of the pericardis which is incorrectly diagnosed as an acute myocardial infarction and treated ФАРМАКИНАЗАтм brought to an exudate into a pericardium, including tamponades. Antibodies against Streptokinasa

In view of the increased probability of the resistance caused by existence of antibodies to Streptokinasa, drug can be inefficient at appointment later than in 5 days after the previous therapy Streptokinasa or drugs which contain Streptokinasa, especially during the period between 5 days and 12 months. In this way the effect of drug can decrease at patients with recently postponed streptococcal infections (streptococcal pharyngitis, an acute glomerulonephritis).

Speed of infusion and preventive use of corticosteroids In an initiation of treatment sometimes note decrease in the ABP, tachycardia or bradycardia (in some cases they can be followed by shock). Therefore in an initiation of treatment infusion needs to be performed slowly. Moreover, preventive use of corticosteroids (for example, from 100 to 200 mg of Methylprednisolonum in 10 min. prior to therapy by drug ФАРМАКИНАЗАтм). Preliminary treatment by heparin or derivatives of coumarin If the patient received previously heparin, effect of this drug needs to be neutralized purpose of protamin of sulfate prior to thrombolytic therapy. Level of thrombin time should not exceed more than twice normal control amount prior to thrombolytic therapy. At the patients who were previously receiving coumarin derivatives prior to infusion of Streptokinasa the indicator of the Ministry of Taxes and Tax Collection (The international normalized relation) has to make less than 1,7 (a prothrombin ratio, at least, of 50%). The arterial puncture If during infusion arises need of a puncture of a vessel, preference should be given to vessels of upper extremities. After a puncture it is necessary to press the place of a puncture within not less than 30 min. and to examine the place of a puncture for identification of symptoms of bleeding. During pregnancy it is possible to appoint drug ФАРМАКИНАЗАтм only after careful assessment of risk and the expected advantage of its use for mother and a fruit. Within the first 18 weeks of pregnancy prescription of Streptokinasa has to be limited only according to vital indications. There is no information concerning use of drug ФАРМАКИНАЗАтм during feeding by a breast.

Side effects:

Bleedings. Bleedings if they arise, as a rule, are limited to places of a puncture. In that case to stop therapy there is no need. Cases of heavy bleedings, including gastrointestinal, a liver and a spleen, urinogenital system, isolated cases of intracranial hemorrhages with complications, including - with a lethal outcome, retroperitoneal bleedings are described. During thrombolytic therapy patients with an acute myocardial infarction in some cases can have bleedings in a pericardium, ruptures of a myocardium are possible. At heavy hemorrhagic complications therapy by Streptokinasa is stopped and appoint proteinase inhibitors, for example, Aprotininum in such doses: at first 500000 KMO (if necessary - to 1 million KMO) then enter on 50000 KMO hourly kapelno to a bleeding stop. Recommend combinations with synthetic anti-fibrinolitic. If necessary appoint blood-coagulation factors.

Allergic reactions. Reactions of immediate type. There can be anaphylactic and anaphylactoid reactions (skin rash, reddening, blisters, suffocation and a bronchospasm).

Late reactions. Separate cases of a serum disease, arthritis, a vasculitis, nephrite and neuroallergic the symptoms (polyneuropathy - a syndrome to Giyena-Barra) arising along with purpose of Streptokinasa are described. If arises allergic reactions use of drug ФАРМАКИНАЗАтм it is necessary to stop immediately (infusion) and to appoint necessary treatment. It is necessary to adhere to the existing medical standards of treatment of shock. After stopping of symptoms of allergic reactions, it is possible to continue treatment homologous fibrinolitik (for example, an urokinase, t-PA). At easy, well controlled reactions there can be justified a drug use continuation. If necessary it is necessary to appoint such additional resources of treatment: a) at easy reactions: GKS and antihistaminic drugs; b) at heavy or life-threatening reactions (for example, an acute anaphylaxis) depending on their weight: slow intravenous injection of adrenaline; to appoint high doses of corticosteroids slowly; if necessary - measures for recovery of volume of the circulating blood, oxygen. Embolisms Risk of a pulmonary embolism at patients with a deep vein thrombosis during treatment by Streptokinasa not above, than at use of one heparin. If during treatment the acute or reversible embolism of a pulmonary artery develops, treatment by Streptokinasa should not differ from planned that allows to reach dissolution of emboluses. During a local thrombolysis in peripheral arteries distal embolization cannot exclude. Several cases of a cholesteric embolism which arose along with thrombolytic therapy are described.

Other reactions. At the beginning of therapy arterial pressure sometimes decreases, tachycardia or bradycardia is observed (in some cases - with shock). Against the background of therapy there can be a headache, a dorsodynia, complaints from digestive tract, muscular pains, temperature increase, and also an adynamy, a febricula, fever. The last, ​​ as a rule, quickly decreases after administration of antipyretic drugs. In some cases there can be a reversible increase in activity of transaminases of serum, and also bilirubin.

Sometimes after intra coronary thrombolytic therapy at patients with an acute myocardial infarction observed not cardiogenic fluid lungs.

In some cases against the background of thrombolytic therapy patients with an acute myocardial infarction can have disturbances of a cordial rhythm, persistent stenocardia, heart failure up to a cardiac standstill and breath. However it is proved that with a myocardial infarction who were treated Streptokinasa the cardiac standstill owing to fibrillation of ventricles occurs at patients less than at usual treatment. Against the background of thrombolytic therapy it was reported about separate cases of vasospasms of a brain which matched on emergence time a cardiovascular hypoxia and cerebral hemorrhages. At a local thrombolysis there can be system side effects.

Interaction with other medicines:

The simultaneous and previous treatment by the anticoagulants or substances influencing formation or function of thrombocytes (for example, inhibitors of aggregation of thrombocytes, dextrans) can increase risk of bleeding. Prior to the beginning of a long system thrombolysis Streptokinasa it is necessary to wait for decrease in effects of the drugs influencing formation and function of thrombocytes. Favorable interaction of drug ФАРМАКИНАЗАтм with acetylsalicylic acid at treatment of an acute myocardial infarction was proved.

Contraindications:

Heavy allergic reactions to administration of drug. Because of the increased risk of the bleedings caused by thrombolytic therapy ФАРМАКИНАЗАтм it should not be applied in the following situations:    

the available or recently postponed bleedings     

all forms of the lowered ability of blood to coagulation, especially - a spontaneous fibrinolysis;    

recently had stroke, intracranial and intraspinaln surgical interventions;    

intracranial new growths recently postponed head injury, existence of new growths with risk of bleeding, acute pancreatitis;    

 uncontrollable hypertensia with systolic arterial pressure over 200 mm of mercury.     

и / or diastolic ABP more than 100 mm of mercury., or hypertensive changes    of a retina of III/IV degrees.

Overdose:

It is not described.

Storage conditions:

To store in the places protected from light unavailable to children at a temperature from 2 °C to 8 °C. A period of validity - 2 years from the date of production. After dissolution drug can be stored in sterile normal saline solution at a temperature from 2 °C to 8 °C within 24 hours without activity loss. Drug ФАРМАКИНАЗАтм is forbidden to be used after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

In a bottle glass, enclosed in a pack.