What is the recommended dose of tenecteplase (tissue plasminogen activator) for a patient with Acute Myocardial Infarction (AMI)?

Tenecteplase Dosing for Acute Myocardial Infarction

Tenecteplase should be administered as a single weight-based intravenous bolus over 5 seconds, with doses ranging from 30 mg to 50 mg based on patient body weight. 1, 2

Weight-Based Dosing Regimen

The recommended dosing is strictly weight-tiered 1, 3, 4, 2:

• <60 kg: 30 mg (6 mL) 1, 3, 4
• 60 to <70 kg: 35 mg (7 mL) 1, 3, 4
• 70 to <80 kg: 40 mg (8 mL) 1, 3, 4
• 80 to <90 kg: 45 mg (9 mL) 1, 3, 4
• ≥90 kg: 50 mg (10 mL) 1, 3, 4

This weight-adjusted approach is critical because total body weight explains 19% of the variability in plasma clearance, with each 10 kg increase in body weight resulting in a 9.6 mL/min increase in clearance. 5

Administration Technique

Administer the entire dose as a single intravenous bolus over 5 seconds. 3, 4, 2 This rapid bolus administration is possible due to tenecteplase's 6-fold prolonged plasma half-life (22 minutes initial, 115 minutes terminal) compared to alteplase (3.5 minutes), which requires a 90-minute infusion. 5, 6

Timing Considerations

• Initiate treatment as soon as possible after symptom onset, ideally within 12 hours. 1, 2
• Fibrinolytic therapy is indicated when primary PCI cannot be performed within 120 minutes of first medical contact. 1, 3
• Pre-hospital administration should be considered when feasible to minimize door-to-needle time. 1, 3
• Greatest mortality benefit occurs in patients presenting within 2 hours of symptom onset with large infarcts. 1

Mandatory Adjunctive Therapy

All patients receiving tenecteplase must receive concurrent antiplatelet and anticoagulation therapy. 1

Antiplatelet Agents

• Aspirin: 150-300 mg oral loading dose (or 80-150 mg IV if oral not possible), followed by 75-100 mg daily. 1, 3
• Clopidogrel:
  • Age ≤75 years: 300 mg loading dose, then 75 mg daily 1, 3
  • Age >75 years: No loading dose, start with 75 mg daily 3

Do not administer prasugrel or ticagrelor with fibrinolysis—these agents have not been studied in this context. 1

Anticoagulation

Enoxaparin is preferred over unfractionated heparin based on superior net clinical benefit. 1, 3

Enoxaparin dosing 3:

• Age <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneous every 12 hours
• Age ≥75 years: No IV bolus, start with 0.75 mg/kg subcutaneous every 12 hours
• Renal impairment (CrCl <30 mL/min): Dose reduction required

Unfractionated heparin alternative 1, 3:

• 60 U/kg IV bolus (maximum 4000 U)
• 12 U/kg/hour infusion (maximum 1000 U/hour)
• Target aPTT 50-75 seconds (aPTT >70 seconds increases bleeding risk) 1

Continue anticoagulation until revascularization or for duration of hospital stay up to 8 days. 1, 3

Absolute Contraindications

Do not administer tenecteplase if any of the following are present 3, 7, 2:

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

Post-Fibrinolytic Management

All patients must be transferred to a PCI-capable center following fibrinolysis. 1, 3, 4

Angiography Timing

• Routine angiography: 3-24 hours after successful fibrinolysis in stable patients 1, 3
• Rescue PCI: Immediately if fibrinolysis fails (<50% ST-segment resolution at 60 minutes) 1, 3, 4
• Emergency PCI: For recurrent ischemia, reocclusion, heart failure, or cardiogenic shock 1

Critical Pitfalls to Avoid

• Failing to use weight-based dosing: Fixed dosing leads to suboptimal plasma concentrations and reduced efficacy. 5, 6
• Administering beyond 12 hours without specific indications: Benefit is not established unless there is ongoing ischemia, large myocardium at risk, or hemodynamic instability with PCI unavailable. 7
• Using excessive enoxaparin doses in elderly patients: Pre-hospital full-dose enoxaparin in patients >75 years significantly increases intracranial hemorrhage risk. 1
• Overlooking contraindications: Even minor contraindications substantially increase bleeding complications, particularly intracranial hemorrhage. 3, 7
• Delaying transfer to PCI-capable center: Transfer should be arranged immediately after tenecteplase administration, not after waiting to assess reperfusion success. 1, 4

Pharmacologic Rationale

Tenecteplase's bioengineering modifications provide 15-fold higher fibrin specificity and 80-fold reduced PAI-1 binding compared to alteplase, allowing single-bolus administration while maintaining equivalent 30-day mortality (6.2% vs 6.2%) with reduced non-cerebral bleeding (26.4% vs 29.0%). 8, 5 The dose-response relationship demonstrates that plasma AUC >320 μg·min/mL (average concentration 3.6 μg/mL) achieves TIMI 3 flow in >75% of patients at 90 minutes, which corresponds to the weight-adjusted dosing regimen of approximately 0.5 mg/kg. 5, 6