STK

recommended following termination of Streptase, Streptokinase, infusion for treatment of pulmonary embolism or deep vein thrombosis to prevent rethrombosis.

Thrombolytic/Plasminogen activator

Streptokinase acts with plasminogen to produce an activator complex that converts plasminogen to plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. Unlike other plasminogen activators, Streptokinase is not an enzyme and does not directly convert plasminogen to plasmin. Instead, Streptokinase forms a 1:1 stoichiometric complex with plasminogen. Formation of this complex induces a conformational change in plasminogen that exposes its active site. This conformationally altered plasminogen then converts additional plasminogen molecules to plasmin. Pharmacokinetics: Plasma Streptokinase concentrations reach a peak at 2 to 3 min after intravenous administration and peak fibrinolytic activity occurs at approximately 30 min depending on the dose. Streptokinase is cleared from the plasma in two phases. The first phase has an average half life of 18 min, and is caused by the presence of antistreptokinase antibody which combines with Streptokinase to produce a complex that is cleared rapidly from the circulation. The second phase is slower, with a half life of approximately 80 min, and reflects the rate at which Streptokinase combines with plasminogen. Hence, the clearance rate will vary according to the availability of plasminogen and the dosage regimen used.

Acute myocardial infarction: Adult: 1.5 MU as a single dose infused over 1 hr immediately after onset of symptoms. Pulmonary thromboembolism; Arteriovenous occlusions: Adult: Loading dose: 250,000 u infused over 30 min. Maintenance: 100,000 units/hr for 24-72 hr depending on the condition to be treated. For cerebral retinal thrombosis, 12 hr may be sufficient Monitor treatment by maintaining thrombin clotting time at 2-4 times normal values. Child: Loading dose: 2500-4000 units/ kg over 30 min, followed by infusion of 500-1000 units/kg/hr, continued until reperfusion occurs, up to 3 days. Initial dose may be estimated by streptokinase resistance test. Monitor treatment by maintaining thrombin clotting time at 2-4 times normal values.

Potentially hazardous interactions: Early administration of Heparin or Hirudin therapy may increase the risk of hemorrhage. Systemic fibrinogenolysis, which inevitably occurs during Streptokinase therapy, impairs coagulation both by causing fibrinogen depletion and through the anti-thrombin effects of fibrin degradation products. This may help protect recanalized vessels from reocclusion and may explain the lack of additional benefit from Heparin. Conversely, early Heparin or Hirudin therapy may increase the risk of hemorrhage. Radiological contrast agents: Some radiological contrast agents such as Diatrizoate and Iohexol, but not ioxaglate, are inhibitors of fibrinolysis by Streptokinase and this may be clinically important. Potentially useful interactions: Antiplatelet therapy: Low-dose aspirin enhances survival in myocardial infarct patients receiving Streptokinase, without increasing the risk of major hemorrhage. Data are presently inadequate to assess the interaction of Streptokinase with more powerful inhibitors of platelet function.

Severe hypertension, recent stroke, cerebral neoplasm, recent history of peptic ulcer disease, ulcerative colitis, pancrestitis, subacute bacterial endocarditis, coagulation defects also due to liver or kidney disease, recent surgery, childbirth. Hypersensitivity, increased risk of cerebral bleeding, trauma. Pregnancy. Active internal bleeding, bleeding GI lesions. Mitral stenosis associated w/ AF. Streptokinase treatment w/in last 12 mth, use after prolonged or traumatic CPR; diabetic retinopathy. Elderly.

Fever, chills, back pain, abdominal pain, nausea, vomiting, arrhythmia, bruising, rash, pruritus, ARF due to embolism & haemorrhage. Cerebral, peripheral & pulmonary embolism. Allergic reactions, liver enzyme abnormalities, hypotension. Haemorrhage; anaphylactic shock.

Streptokinase should be given during pregnancy only when benefit outweighs risk. The human placenta essentially prevents passage of SK to the fetus. The minimal amount of SK that reaches the fetal circulation is not enough to cause fibrinolytic effects in the fetus. Streptokinase in lactation is not available.

Streptokinase is to be stored at 2° to 8°C. Once reconstituted with physiological saline, the physico-chemical stability has been demonstrated for 24 hours at 2° to 8°C. From a microbiological point of view and as S-kinase contains no preservative, the reconstituted product should be used immediately. If it is not administered immediately, storage shall not exceed 24 hours at 2° to 8°C.

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