What are the dosing guidelines for reteplase and tenecteplase in patients requiring thrombolytic therapy?

Dosing Guidelines for Reteplase and Tenecteplase

Reteplase Dosing

Reteplase is administered as two 10-unit intravenous bolus injections given 30 minutes apart, regardless of patient weight. 1, 2

Administration Protocol

• First bolus: 10 units IV over 2 minutes 2, 3
• Second bolus: 10 units IV over 2 minutes, given exactly 30 minutes after the first bolus 1, 2, 3
• This non-weight-based regimen simplifies administration and minimizes dosing errors under time pressure 3, 4

Key Advantages

• The double-bolus regimen is particularly conducive to prehospital initiation of thrombolytic therapy, reducing critical time to treatment 3, 4
• Reteplase achieves superior early coronary patency compared to alteplase, with 60-minute TIMI 3 flow rates equivalent to alteplase at 90 minutes 2

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Tenecteplase Dosing

Tenecteplase is administered as a single weight-based intravenous bolus over 5 seconds. 1, 5

Weight-Based Dosing Schedule

• <60 kg: 30 mg (6 mL) 1, 5
• 60 to <70 kg: 35 mg (7 mL) 1, 5
• 70 to <80 kg: 40 mg (8 mL) 1, 5
• 80 to <90 kg: 45 mg (9 mL) 1, 5
• ≥90 kg: 50 mg (10 mL) 1, 5

Administration Advantages

• Single bolus administration over 5 seconds makes tenecteplase the simplest fibrinolytic to administer 5
• Pre-hospital administration is preferred when feasible to minimize time to treatment 5

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Mandatory Adjunctive Therapy for Both Agents

Antiplatelet Therapy

• Aspirin: Loading dose of 150-325 mg orally (or 80-150 mg IV if oral not possible), followed by 75-100 mg daily 1, 5, 2
• Clopidogrel:
  • For patients ≤75 years: 300 mg loading dose, then 75 mg daily 1, 2
  • For patients >75 years with tenecteplase: no loading dose, start with 75 mg daily 5

Anticoagulation (Required)

Enoxaparin is preferred over unfractionated heparin: 1, 2

• For patients <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneous every 12 hours 2
• For patients ≥75 years: No IV bolus; start with 0.75 mg/kg subcutaneous every 12 hours 2

Unfractionated heparin (alternative): 1, 2

• 60 U/kg IV bolus (maximum 4000 U) followed by 12 U/kg/hour infusion (maximum 1000 U/hour) for 24-48 hours 1, 2
• Target aPTT: 50-70 seconds (1.5 to 2.0 times control), monitored at 3,6,12, and 24 hours 1

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Critical Timing Considerations

• Fibrinolytic therapy is indicated when primary PCI cannot be performed within 120 minutes of first medical contact 5, 2
• Greatest benefit occurs within the first 12 hours after symptom onset, with maximal benefit in patients presenting within 2 hours 5, 2
• Treatment can be initiated up to 12 hours from symptom onset 6

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Post-Fibrinolytic Management

All patients must be transferred to a PCI-capable center following fibrinolysis. 5, 2

Angiography Timing

• Routine angiography: Recommended 3-24 hours after successful fibrinolysis in stable patients 1, 2
• Emergency angiography: Indicated immediately if fibrinolysis fails (<50% ST-segment resolution at 60-90 minutes) 5, 2
• Recurrent ischemia: Emergency angiography indicated for heart failure/shock or evidence of reocclusion 1

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Re-administration Considerations

Tenecteplase can be re-administered if clinically indicated, unlike streptokinase which is absolutely contraindicated for at least 6 months. 7

• Tenecteplase does not cause antibody formation, allowing for re-administration in cases of reocclusion or reinfarction with recurrent ST-segment elevation 7
• No specific time-based contraindication exists for repeat dosing of tenecteplase 7
• The decision to re-administer must weigh bleeding risk against reperfusion benefit, with reassessment of all absolute contraindications 7
• Reteplase similarly can be re-administered as it is fibrin-specific and does not cause antibody formation 7

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Absolute Contraindications (Both Agents)

• Any prior intracranial hemorrhage 5, 2
• Known structural cerebral vascular lesion or malignant intracranial neoplasm 5
• Ischemic stroke within 3-6 months 5, 2
• Suspected aortic dissection 5, 2
• Active bleeding or bleeding diathesis 5, 2
• Significant closed-head or facial trauma within 3 months 5
• Severe uncontrolled hypertension (SBP >180 mmHg or DBP >110 mmHg) 5, 2

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Comparative Efficacy

• Reteplase and alteplase demonstrate equivalent 30-day mortality rates (7.47% vs 7.24%, P=0.54) 8
• Reteplase and streptokinase show equivalent 35-day mortality rates (9.02% vs 9.53%) 6
• Stroke rates are similar across agents: reteplase 1.64%, alteplase 1.79% 8
• Bleeding complications are comparable among fibrin-specific agents 3, 4