What is the recommended dose of tenecteplase (tissue plasminogen activator) for acute myocardial infarction (heart attack)?

Tenecteplase Dosing for Acute Myocardial Infarction

Administer tenecteplase as a single intravenous bolus using weight-based dosing: 30 mg for patients <60 kg, 35 mg for 60-<70 kg, 40 mg for 70-<80 kg, 45 mg for 80-<90 kg, and 50 mg for patients ≥90 kg. 1

Weight-Based Dosing Algorithm

The European Society of Cardiology established a five-tier weight-based regimen that optimizes therapeutic plasma concentrations while minimizing bleeding risk 1:

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

This weight-adjusted approach is supported by pharmacokinetic data showing that total bodyweight explains 19% of clearance variability, with each 10 kg increase in bodyweight resulting in a 9.6 mL/min increase in clearance 2. The dose range of 30-50 mg (approximately 0.5 mg/kg) achieves plasma AUC values that provide optimal TIMI 3 coronary flow at 90 minutes 3.

Administration Technique

Administer the entire dose as a single intravenous bolus over 5-10 seconds 1. This simplified administration is possible because tenecteplase has an 80-fold reduced binding to PAI-1 and a 6-fold prolonged plasma half-life (22 minutes initial phase versus 3.5 minutes for alteplase), eliminating the need for the 90-minute infusion required with alteplase 2.

Timing Requirements

• Must administer within 12 hours of symptom onset, with greatest benefit occurring with earlier administration 1
• Indicated when primary PCI cannot be performed by an experienced team within 120 minutes of first medical contact 1
• For patients presenting very early (<2 hours) with large infarcts and low bleeding risk, consider fibrinolysis if time from first medical contact to balloon inflation exceeds 90 minutes 1

Mandatory Adjunctive Antiplatelet Therapy

You must administer dual antiplatelet therapy immediately 1:

Aspirin

• Loading dose: 150-500 mg orally OR 250 mg IV if oral route unavailable 1
• Maintenance: 75-100 mg daily 1

Clopidogrel

• Age ≤75 years: 300 mg loading dose orally, then 75 mg daily 1
• Age >75 years: No loading dose; start with 75 mg daily maintenance 1

Mandatory Anticoagulation

Anticoagulation is required until revascularization or for the duration of hospital stay up to 8 days 1. Enoxaparin is preferred over unfractionated heparin 1:

Enoxaparin (Preferred)

• Age <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneous every 12 hours (maximum 100 mg for first two doses) 1
• Age ≥75 years: No IV bolus; start with 0.75 mg/kg subcutaneous every 12 hours (maximum 75 mg for first two doses) 1
• Renal impairment (CrCl <30 mL/min): Subcutaneous doses given once every 24 hours regardless of age 1

Unfractionated Heparin (Alternative)

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

Post-Administration Monitoring and Management

Immediate Monitoring (60-180 minutes)

Monitor ST-segment elevation, cardiac rhythm, and clinical symptoms 1. Signs of successful reperfusion include relief of symptoms, hemodynamic/electrical stability, and ≥50% reduction of initial ST-segment elevation on follow-up ECG at 60-90 minutes 1.

Transfer Requirements

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

Rescue PCI Indication

Perform rescue PCI immediately if fibrinolysis fails (<50% ST-segment resolution at 60 minutes) 1.

Routine Angiography Timing

For stable patients after successful fibrinolysis, perform routine angiography with view to revascularization at 3-24 hours 1.

Evidence Supporting Tenecteplase

Large-scale trials demonstrate that tenecteplase has equivalent 30-day mortality to alteplase (approximately 6.2%) with fewer non-cerebral bleeding complications (26.43% vs 28.95%, p=0.0003) 4. The ASSENT-2 trial involving 16,949 patients showed similar rates of intracranial hemorrhage (0.93% vs 0.94%) and stroke (1.78% vs 1.66%) between tenecteplase and alteplase 4. Tenecteplase demonstrated reduced mortality in patients receiving treatment more than 4 hours after symptom onset (7% vs 9.2%, p=0.018) 4.

Critical Pitfall to Avoid

Do not use fixed dosing—the weight-based regimen is essential because plasma clearance varies significantly with bodyweight, and underdosing reduces efficacy while overdosing increases bleeding risk 2, 3. More than 75% of patients achieve normal coronary flow when their plasma AUC exceeds 320 μg·min/mL, which requires proper weight-adjusted dosing 2.