What is the recommended dosage of streptokinase for the management of myocardial infarction (MI)?

Streptokinase Dosage in Myocardial Infarction

The recommended dose of streptokinase for acute myocardial infarction is 1.5 million units administered intravenously over 30-60 minutes. 1, 2

Standard Dosing Protocol

Administer 1.5 million units of streptokinase in 100 mL of 5% dextrose or 0.9% saline intravenously over 30-60 minutes. 1, 2 This dose has been validated across multiple large-scale trials and remains the guideline-recommended regimen from both the European Society of Cardiology and American College of Cardiology/American Heart Association. 1

Timing Considerations

• Streptokinase should be administered within 12 hours of symptom onset when primary PCI cannot be performed within 120 minutes of first medical contact. 1, 2
• Treatment within 3 hours of symptom onset provides optimal benefit, though efficacy extends to 12 hours. 1
• Between 12-24 hours after symptom onset, streptokinase may be reasonable only if there is evidence of ongoing ischemia with a large area of myocardium at risk or hemodynamic instability. 1

Mandatory Adjunctive Antiplatelet Therapy

Aspirin must be co-administered with streptokinase:

• Loading dose: 150-325 mg orally (chewed, non-enteric coated) or 250-500 mg IV if oral route not possible 1, 2
• Maintenance: 75-100 mg daily indefinitely 1, 2
• The benefits of aspirin and streptokinase are additive, as demonstrated in the ISIS-2 trial. 1, 2

Clopidogrel should be added:

• Loading dose: 300 mg orally if age ≤75 years; 75 mg if age >75 years 1, 2
• Maintenance: 75 mg daily for at least 14 days, up to 1 year 1, 2

Required Anticoagulation

Anticoagulation is mandatory until revascularization or for hospital duration up to 8 days. 1, 2 Choose one of the following:

Preferred option with streptokinase:

• Fondaparinux: 2.5 mg IV bolus, then 2.5 mg subcutaneously once daily 2

Alternative options:

• Enoxaparin (preferred over unfractionated heparin): 1, 2

  • Age <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneously every 12 hours
  • Age ≥75 years: No IV bolus; 0.75 mg/kg subcutaneously every 12 hours

• Unfractionated heparin: 1, 2

  • 60 U/kg IV bolus (maximum 4000 U)
  • 12 U/kg/hour IV infusion (maximum 1000 U/hour) for 24-48 hours
  • Target aPTT: 50-70 seconds (1.5-2.0 times control)
  • Monitor aPTT at 3,6,12, and 24 hours 1

Critical Contraindications

Absolute contraindications to streptokinase include: 1

• Prior streptokinase or anistreplase administration (antibodies persist for at least 10 years) 1, 2
• Hemorrhagic stroke or stroke of unknown origin at any time
• Ischemic stroke in preceding 6 months
• Central nervous system damage or neoplasms
• Recent major trauma/surgery/head injury (within 3 weeks)
• Gastrointestinal bleeding within last month
• Known bleeding disorder
• Aortic dissection

Post-Administration Monitoring and Management

Monitor for successful reperfusion at 60-90 minutes: 1, 2

• Relief of chest pain
• Reduction of ST-segment elevation by ≥50%
• Hemodynamic and electrical stability
• Typical reperfusion arrhythmias

Transfer all patients to a PCI-capable center immediately after fibrinolysis. 1, 2

Perform angiography with view to revascularization: 1, 2

• Emergency angiography immediately if: Heart failure/shock, failed fibrinolysis (<50% ST-segment resolution), hemodynamic/electrical instability, or worsening ischemia 1, 2
• Routine angiography: 3-24 hours after successful fibrinolysis 1, 2

Important Safety Considerations

Common complications to monitor: 2

• Hypotension (common with streptokinase administration)
• Bleeding complications (occur in 4-13% of patients)
• Intracranial hemorrhage (0.9-1.0% incidence)

Risk factors for intracranial hemorrhage include: 2

• Lower body weight
• Female sex
• Previous cerebrovascular disease
• Systolic/diastolic hypertension on admission

Never re-administer streptokinase due to antibody formation that impairs activity and increases allergic reaction risk. 1, 2 If repeat fibrinolysis is needed, use alteplase, reteplase, or tenecteplase instead. 1

Alternative Dosing Evidence

While the standard 1.5 million unit dose is guideline-recommended, research has explored lower doses (500,000-750,000 units over 30 minutes). 3 However, these lower doses lack guideline endorsement and should not be used in routine practice, as the 1.5 million unit dose remains the evidence-based standard with established safety and efficacy profiles. 1