What is the recommended dose of tenecteplase (TNK-tPA) for treating pulmonary embolism?

Tenecteplase Dosing for Pulmonary Embolism

For pulmonary embolism, administer tenecteplase as a single weight-based intravenous bolus using the standard STEMI dosing regimen: 30 mg for patients <60 kg, 35 mg for 60-69 kg, 40 mg for 70-79 kg, 45 mg for 80-89 kg, and 50 mg for patients ≥90 kg, given over 5 seconds. 1

Weight-Based Dosing Protocol

The dosing is straightforward and follows a tiered weight-based approach endorsed by both the American Heart Association and American College of Cardiology 1:

• <60 kg: 30 mg 1
• 60-69 kg: 35 mg 1
• 70-79 kg: 40 mg 1
• 80-89 kg: 45 mg 1
• ≥90 kg: 50 mg 1

This is identical to the STEMI dosing regimen, which has been validated in the landmark PEITHO trial for pulmonary embolism 1. The dose is administered as a single IV bolus over 5 seconds 1, making it operationally simpler than alteplase which requires a 2-hour infusion 2.

Clinical Indications by Risk Stratification

High-risk (massive) PE with hemodynamic instability is the primary indication for tenecteplase, defined as hypotension, shock, or need for vasopressor support 1. This carries a Class IIa recommendation from the European Society of Cardiology 1.

For intermediate-risk PE, the evidence is more nuanced 1. The PEITHO trial demonstrated that tenecteplase reduces death/decompensation at 7 days in intermediate-risk PE, but causes 2% intracranial hemorrhage and 6.3% extracranial bleeding 1. Routine use in intermediate-risk PE is not recommended, though it may be considered in carefully selected patients after thorough risk-benefit assessment 1.

Low-risk PE should be treated with anticoagulation alone, not thrombolysis 2.

Administration Protocol

• Give tenecteplase before or concurrent with anticoagulation (unfractionated heparin or LMWH) 1
• After the tenecteplase bolus, initiate heparin infusion once the aPTT falls below twice the upper limit of normal 1
• Do not delay administration in massive PE with hemodynamic collapse while awaiting imaging confirmation—clinical diagnosis may be sufficient when cardiac arrest is imminent 1

Expected Hemodynamic Response

Tenecteplase produces rapid hemodynamic improvement 1, 2:

• 30-35% reduction in pulmonary perfusion defect at 24 hours 1
• 12% decrease in vascular obstruction within 2 hours 2
• 30% reduction in mean pulmonary arterial pressure 2
• Approximately 92% of patients show clinical and echocardiographic improvement within 36 hours 1, 2

Absolute Contraindications

Do not administer tenecteplase if any of the following are present 1:

• Prior intracranial hemorrhage 1
• Known structural cerebral vascular lesion 1
• Known malignant intracranial neoplasm 1
• Recent stroke (within 3 months for ischemic stroke) 1
• Recent significant head trauma or intracranial/intraspinal surgery 1
• Active bleeding or bleeding diathesis 1

Bleeding Risk Profile

The bleeding risk is substantial and must be weighed against mortality benefit 1, 2:

• Major bleeding: approximately 13% 1, 2
• Intracranial hemorrhage: 1.8-2% 1, 2
• Fatal hemorrhage: approximately 1.8-2% 2

Special Populations: Elderly Patients

Elderly patients (>75 years) have significantly higher bleeding risk, particularly intracranial hemorrhage, and may require dose reduction 1. One case report documented successful treatment of a patient over 90 years with a reduced dose of 17.5 mg (0.37 mg/kg) without clinically significant bleeding 3, though this approach requires further validation and should only be considered when the mortality risk from PE clearly outweighs the bleeding risk.

Critical Pitfalls to Avoid

• Do not use tenecteplase routinely in intermediate-risk PE without careful risk-benefit assessment given the 2% stroke risk 1
• Do not delay administration in massive PE awaiting confirmatory imaging when hemodynamic collapse is imminent 1
• Do not re-administer tenecteplase if re-occlusion occurs, as this may lead to excessive bleeding complications 4

Alternative Thrombolytic Options

If tenecteplase is unavailable, alteplase 100 mg over 2 hours or a 0.6 mg/kg bolus over 15 minutes are acceptable alternatives for massive PE 1, 2. Alteplase has more extensive validation in large PE trials and is the most established thrombolytic for PE 5.