Streptokinase Indication

Acute Evolving Transmural Myocardial Infarction: Streptase, Streptokinase, is indicated for use in the management of acute myocardial infarction (AMI) in adults, for the lysis of intracoronary thrombi, the improvement of ventricular function, and the reduction ofmortality associated with AMI, when administered by either the intravenous or the intracoronary route, as well as for the reduction of infarct size and congestive heart failureassociated with AMI when administered by the intravenous route. Earlier administration of Streptokinase is correlated with greater clinical benefit. (See CLINICAL PHARMACOLOGY.) Pulmonary Embolism: Streptase, Streptokinase, is indicated for the lysis of objectively diagnosed (angiography or lung scan) pulmonary emboli, involving obstruction of blood flow to a lobe or multiple segments, with or without unstable hemodynamics. Deep Vein Thrombosis: Streptase, Streptokinase, is indicated for the lysis of objectively diagnosed (preferably ascending venography), acute, extensive thrombi of the deep veins such as those involving the popliteal and more proximal vessels. Arterial Thrombosis or Embolism: Streptase, Streptokinase, is indicated for the lysis of acute arterial thrombi and emboli. Streptokinase is not indicated for arterial emboli originating from the left side of the heart due to the risk of new embolic phenomena such as cerebral embolism. Occlusion of Arteriovenous Cannulae: Streptase, Streptokinase, is indicated as an alternative to surgical revision for clearing totally or partially occluded arteriovenous cannulae when acceptable flow cannot be achieved.

Mechanism Dosage
Acute Evolving Transmural Myocardial Infarction: Administer Streptokinase as soon as possible after onset of symptoms. The greatest benefit in mortality reduction was observed when Streptokinase was administered within four hours, but statistically significant benefit has been reported up to 24 hours (see CLINICAL PHARMACOLOGY ). ROUTE Intravenous infusion Intracoronary infusion TOTAL DOSE 1,500,000 IU 140,000 IU DOSAGE/DURATION 1,500,000 IU within 60 min. 20,000 IU by bolus followed by 2,000 IU/min. for 60 min.

Pulmonary Embolism, Deep Vein Thrombosis, Arterial Thrombosis or Embolism: Streptase, Streptokinase, treatment should be instituted as soon as possible after onset of the thrombotic event, preferably within 7 days. Any delay in instituting lytic therapy to evaluate the effect of heparin therapy decreases the potential for optimal efficacy. Since human exposure to streptococci is common, antibodies to Streptokinase are prevalent. Thus, a loading dose of Streptokinase sufficient to neutralize these antibodies is required. A dose of 250,000 IU of Streptokinase infused into a peripheral vein over 30 minutes has been found appropriate in over 90% of patients. Furthermore, if the thrombintime or any other parameter of lysis after 4 hours of therapy is not significantly different from the normal control level, discontinue Streptokinase because excessive resistanceis present. INDICATION Pulmonary Embolism Deep Vein Thrombosis Arterial Thrombosis or Embolism LOADING DOSE IV INFUSION DOSAGE/DURATION

100,000 IU/hr for 24 hr 250,000 IU/30 min. (72 hrs if concurrent DVT is suspected). 250,000 IU/30 min. 100,000 IU/hr for 72 hr 250,000 IU/30min. 100,000 IU/hr for 24-72 hr

Arteriovenous Cannulae Occlusion: Before using Streptase, Streptokinase, an attempt should be made to clear the cannula by careful syringe technique, using heparinizedsaline solution. If adequate flow is not reestablished, Streptokinase may be employed. Allow the effect of any pretreatment anticoagulants to diminish. Instill 250,000 IU Streptokinase in 2 mL of solution into each occluded limb of the cannula slowly. Clamp off cannula limb(s) for 2 hours. Observe the patient closely for possible adverse effects. After treatment, aspirate contents of infused cannula limb(s), flush with saline, reconnect cannula. Pediatric Patients: Specific dosage and administration recommendations cannot be made based on the limited data available. However, published experience generally used loading and continuous infusion doses administered on a weight-adjusted basis.

TABLE 1: SUGGESTED DILUTIONS AND INFUSION RATES VIAL SIZE (IU) TOTAL SOLUTION VOLUME

DOSAGE I. Acute Myocardial Infarction A. Intravenous Infusion B. Intracoronary Infusion 1. 20,000 IU bolus 2. 2,000 IU/minute for 60 minutes

INFUSION RATE

1,500,000 45 mL 250,000 125 mL

Infuse 45 mL within 60 min.

>1. Loading Dose of 10 mL >2. Then 60 mL/hour

II. Pulmonary Embolism, Deep Vein Thrombosis, Arterial Thrombosis or Embolism Intravenous Infusion A. 1. 250,000 IU loading dose over 30 minutes 2. 100,000 IU/hour maintenance dose 1,500,000 infusion bottle 45 mL 1,500,000 90 mL >1. Infuse 30 mL/hour for 30 minutes 2. Infuse 6 mL per hour 1. 15 mL/hour for 30 minutes 2. Infuse 3 mL per hour

B. SAME

Side effects
Bleeding: Following intravenous high-dose brief-duration Streptokinase therapy in acute myocardial infarction, severe bleeding complications requiring transfusion are extremely rare (0.3-0.5%), and combined therapy with low dose aspirin does not appear to increase the risk of major bleeding. The addition of aspirin to Streptokinase may cause a slight increase in the risk of minor bleeding (3.1% without aspirin vs. 3.9% with) . Streptokinase will cause lysis of hemostatic fibrin deposits such as those occurring at sites of needle punctures, particularly when infused over several hours, and bleeding may occur from such sites. In order to minimize the risk of bleeding during treatment with Streptokinase, venipunctures and physical handling of the patient should be performed carefully and as infrequently as possible, and intramuscular injections must be avoided. Should an arterial puncture be necessary during intravenous therapy, upper extremity vessels are preferable. Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding. In the following conditions the risks of therapy may be increased and should be weighed against the anticipated benefits.
(2)

Recent (within 10 days) major surgery, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels

Recent (within 10 days) serious gastrointestinal bleeding Recent (within 10 days) trauma including cardiopulmonary resuscitation Hypertension: systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation Subacute bacterial endocarditis Hemostatic defects including those secondary to severe hepatic or renal disease Pregnancy Age >75 years Cerebrovascular disease Diabetic hemorrhagic retinopathy Septic thrombophlebitis or occluded AV cannula at seriously infected site Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location. Should serious spontaneous bleeding (not controllable by local pressure) occur, the infusion of Streptase, Streptokinase, should be terminated immediately and treatment instituted as described under ADVERSE REACTIONS. Bleeding into the pericardium, sometimes associated with myocardial rupture, has been seen in individual cases and has resulted in fatalities. Arrhythmias: Rapid lysis of coronary thrombi has been shown to cause reperfusionatrial or ventricular dysrhythmias requiring immediate treatment. Careful monitoring forarrhythmia is recommended during and immediately following administration of Streptase, Streptokinase, for acute myocardial infarction. Occasionally, tachycardia andbradycardia have been observed. Hypotension: Hypotension, sometimes severe, not secondary to bleeding oranaphylaxis has been observed during intravenous Streptase, Streptokinase, infusion in 1% to 10% of patients. Patients should be monitored closely and, should symptomatic or alarming hypotension occur, appropriate treatment should be administered. This treatment may include a decrease in the intravenous Streptokinase infusion rate. Smallerhypotensive effects are common and have not required treatment. Cholesterol Embolism: Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g.,cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy. Clinical features of cholesterol embolism may include livedo reticularis, "purple toe" syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis. Other: Non-cardiogenic pulmonary edema has been reported rarely in patients treated with Streptase, Streptokinase. The risk of this appears greatest in patients who have large myocardial infarctions and are undergoing thrombolytic therapy by the intracoronary route.

Contraindications
Because thrombolytic therapy increases the risk of bleeding, Streptase, Streptokinase, is contraindicated in the following situations:

active internal bleeding recent (within 2 months) cerebrovascular accident, intracranial or intraspinal surgery (see WARNINGS) intracranial neoplasm severe uncontrolled hypertension Streptokinase should not be administered to patients having experienced severe allergic reaction to the product.

Management