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

Tenecteplase Dosing for Pulmonary Embolism

For high-risk (massive) pulmonary embolism with hemodynamic instability, administer tenecteplase as a single weight-adjusted intravenous bolus using the standard STEMI dosing regimen: 30-50 mg based on body weight, given over 5 seconds. 1, 2

Weight-Based Dosing Regimen

The recommended weight-adjusted dosing is 1, 2:

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

This single-bolus regimen is the most convenient for emergency administration and has been validated in clinical trials. 1

Clinical Indications for Tenecteplase

High-Risk (Massive) PE: Tenecteplase is indicated for patients with hemodynamic instability, defined as hypotension (systolic BP <90 mmHg), shock, or need for vasopressor support. 1, 2 This represents a Class IIa recommendation where thrombolysis can be lifesaving. 1

Intermediate-Risk PE: The evidence is more nuanced here. The 2014 ESC PEITHO trial showed tenecteplase reduced hemodynamic decompensation but increased major bleeding (6.3% vs 1.5%) and hemorrhagic stroke (2% vs 0.2%). 1 Therefore, routine use in intermediate-risk PE is not recommended, though it may be considered in carefully selected patients with intermediate-high-risk features. 1

Cardiac Arrest from PE: In confirmed PE causing cardiac arrest, tenecteplase is a reasonable emergency treatment option even when standard contraindications exist, as the mortality without clot-directed therapy is extremely high. 1 Standard contraindications may be superseded by the need for potentially lifesaving intervention. 1

Administration Protocol

• Give tenecteplase as a single IV bolus over 5 seconds 1, 2
• Administer before or concurrent with anticoagulation (unfractionated heparin or LMWH) 1
• Systemic IV administration is preferred; catheter-directed therapy offers no proven advantage 1
• Treatment is most effective within 48 hours of symptom onset but can be beneficial up to 6-14 days 1

Hemodynamic Response

Expect rapid improvement in hemodynamics 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

Bleeding Risk and Contraindications

Major bleeding rates 1, 2:

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

Absolute contraindications 2:

• Any prior intracranial hemorrhage
• Known structural cerebral vascular lesion
• Known malignant intracranial neoplasm
• Ischemic stroke within 3 months
• Active bleeding or bleeding diathesis
• Suspected aortic dissection

Relative contraindications 2:

• Recent surgery (within 7 days)
• Prolonged cardiopulmonary resuscitation
• Pregnancy (particularly within 6 hours of delivery or early postpartum)
• Peptic ulcer disease

Special Populations

Elderly patients (>75 years): Consider the significantly higher bleeding risk, particularly intracranial hemorrhage. 1 Some evidence from STEMI trials suggests a 50% dose reduction in elderly patients reduces stroke risk, though this has not been formally studied in PE. 1

Reduced-dose regimens: While full-dose tenecteplase is standard, emerging case reports suggest reduced doses (e.g., 17.5 mg or 0.37 mg/kg) may be effective in very high-risk elderly patients, though this remains investigational. 3

Critical Pitfalls to Avoid

• Do not delay tenecteplase in massive PE with hemodynamic collapse while awaiting imaging confirmation—clinical diagnosis may be sufficient when cardiac arrest is imminent 1
• Do not use tenecteplase routinely in intermediate-risk PE without careful risk-benefit assessment given the 2% stroke risk 1
• Do not forget to transfer patients to facilities capable of rescue interventions (surgical embolectomy, ECPR) if thrombolysis fails 1
• Do not overlook absolute contraindications except in truly life-threatening situations where death is imminent 1, 2

Alternative Thrombolytic Regimens

If tenecteplase is unavailable, alteplase 100 mg over 2 hours or a 50 mg bolus are acceptable alternatives for massive PE. 1 Accelerated 2-hour regimens are preferable to prolonged 12-24 hour infusions of first-generation agents. 1