Description of Streptokinase

Streptokinase is a nonenzymatic protein produced by group C beta-hemolytic streptococci. Clinically, it is used as a parenteral thrombolytic agent in the management of acute myocardial infarction, pulmonary embolism, deep vein thrombosis, occluded arteriovenous cannulae, and acute arterial thrombosis and embolism. Streptokinase is not recommended in patients with acute ischemic stroke due to lack of benefit and an increased risk of intracranial hemorrhage and mortality. Unlike urokinase, repeated administration of streptokinase can result in tolerance and/or hypersensitivity. Streptokinase is considerably less expensive than other thrombolytics. Streptokinase is recommended for use in patients presenting with ST segment elevation myocardial infarction (STEMI) and symptoms of acute ischemia of 12 hours or less in duration or in high-risk patients with STEMI and ongoing symptoms of ischemia or hemodynamic compromise of 12 to 24 hours in duration. However, in patients with STEMI and symptom duration of less than 6 hours, guidelines recommend alteplase or tenecteplase over streptokinase. Guidelines also recommend against the use of streptokinase with any GP IIb/IIIa inhibitor (e.g., abciximab, eptifibatide, tirofiban).

Mechanism of Action of Streptokinase

Streptokinase facilitates thrombolysis through formation of an activator complex with plasminogen. Streptokinase exerts its action indirectly through this complex to cleave the arginine-valine bond of plasminogen, resulting in the formation of plasmin. Plasmin degrades fibrin and fibrinogen as well as the procoagulant factors V and VIII. The activator complex also diffuses into the thrombus, activating preplasmin-2, which lyses fibrin. Following administration of high dosages of streptokinase, plasmin inhibitors, including alpha-2-antiplasmin and alpha-2-macroglobulin, are depleted. Excessively large doses, however, can deplete the plasminogen pool, causing a decrease in the amount of fibrin that can be lysed. The degradation products of fibrin and fibrinogen exert a clinically significant anticoagulant effect. This effect may be the result of impaired fibrin polymerization and/or platelet function. Streptokinase also has been reported to decrease erythrocyte aggregation and plasma viscosity, which may be the result of a decrease in fibrinogen concentration.

Pharmacokinetics of Streptokinase

Streptokinase is administered via intravenous or intracoronary infusion. Although distribution has not been fully elucidated, streptokinase can cross the placenta in minimal amounts (see Contraindications). Antistreptokinase antibodies also cross the placenta, but it is unknown if excretion into breast milk occurs. The plasma half-life of the activator complex is 23 minutes.  The metabolites of streptokinase have not been indentified. Blood concentrations and clearance rates depend on the availability of substrates and the concentration of circulating antibodies. Elimination of streptokinase is not well defined.

Route-Specific Pharmacokinetics
Intravenous Route
Reperfusion of the myocardium usually occurs within 20 minutes to 2 hours after streptokinase administration. Antistreptokinase antibodies clear the drug rapidly from the circulation following IV infusion

Generic Name

• Streptokinase

• Streptase

• Thrombolytic
• Tissue Plasminogen Activator

• Acute myocardial infarction: Adult
• Arterial thrombosis: Adult
• Cannulation of arteriovenous dialysis fistula, Clearance: Adult
• Deep venous thrombosis: Adult
• Pulmonary embolism: Adult

Common Effects

• Cardiovascular: Hypotension (1% to 10% )
• Other: Fever (33% .)

• Cardiovascular: Cardiac dysrhythmia, Cardiac rupture due to and following acute myocardial infarction, Myocardial infarction
• Gastrointestinal: Nontraumatic splenic rupture
• Hematologic: Cholesterol embolus syndrome, Hemorrhage, Major (0.1% to 15.6% )
• Immunologic: Anaphylaxis (0.1% )
• Neurologic: Intracranial hemorrhage
• Ophthalmic: Visual acuity, no light perception
• Respiratory: Acute respiratory distress syndrome

Administration

• Gently roll and tilt vial when reconstituting rather than shake or agitate to prevent foaming
• Slight flocculation (thin transparent fibers) may occur but does not interfere with safe use of the solution
• Do not add other medications to the streptokinase vial
• Intravenous: reconstitute the contents of each streptokinase 1,500,000 international units vial with 5 mL of NS or D5W, dilute by slowly adding reconstituted solution to a glass or plastic container with NS or D5W, infuse with a volumetric infusion pump
• Intravenous: do not use drop-counting infusion methods, since drug may alter drop size
• Intravenous: solutions diluted in glass containers with NS can be filtered using a 0.8 micron or larger (cellulose) or a 0.22 micron or larger (PVC-acrylic polymer) in-line filter
• Intracoronary: reconstitute each streptokinase 250,000 international units vial needed with 5 mL of NS or D5W, dilute by slowly adding reconstituted solution to a glass or plastic container with NS or D5W, infuse with a volumetric infusion pump
• Intracoronary: do not use drop-counting infusion methods, since drug may alter drop size
• Intracoronary: solutions diluted in glass containers with NS can be filtered using a 0.8 micron or larger (cellulose) or a 0.22 micron or larger (PVC-acrylic polymer) in-line filter
• Instillation: (arteriovenous cannula) reconstitute 250,000 international units with 2 mL NS or D5W
• Instillation: (arteriovenous cannula) clear the cannula by careful syringe technique using heparinized saline
• Instillation: (arteriovenous cannula) instill reconstituted streptokinase solution intravenously into each occluded limb of the catheter slowly
• Instillation: (arteriovenous cannula) clamp off the cannula limb(s) for 2 hours, aspirate contents of cannula limb(s), flush with saline, and reconnect cannula

• Acute myocardial infarction: (intravenous) 1,500,000 international units IV infused over 60 min
• Acute myocardial infarction: (intracoronary) 20,000 international units by INTRACORONARY bolus, then 2000 to 4000 international units/min for 30 to 90 min
• Arterial thrombosis: loading dose, 250,000 international units IV over 30 min, then 100,000 international units/hr for 24 hr
• Blocked catheter: instill 10,000 international units into occluded catheter for 1 h, aspirate contents and flush with saline
• Cannulation of arteriovenous dialysis fistula, Clearance: instill 250,000 international units/2 mL into each occluded limb of the catheter, clamp off for 2 h, aspirate contents of infused cannula limb(s), flush with saline
• Deep venous thrombosis: loading dose, 250,000 international units IV over 30 min, then 100,000 international units/hr for 72 hr
• Pulmonary embolism: loading dose, 250,000 international units IV over 30 min, then 100,000 international units/hr for 24 hr (72 hr if concurrent deep vein thrombosis is suspected)

• Arterial thrombosis: loading dose, 2000 units/kg; maintenance dose, 2000 units/kg/hr for 6 to 12 hr
• Arterial thrombosis: loading dose, 1000 international units/kg IV over 5-30 min; continuous infusion, 1000 international units/kg/hr for up to 24 hr
• Arterial thrombosis: (following cardiac catheterization) initial, 1000, 2000 or 3000 units/kg IV given over 30 minutes; then 1000, 1500 or 2000 units/kg/hour IV infusion or 3000 units/kg IV bolus, then 1000 units/kg/hour IV infusion administered 48 hours after catheterization for 4 to 20 hours .