In an adult with massive pulmonary embolism presenting with sustained hypotension or shock, is tenecteplase approved for use, and what is the recommended off‑label weight‑based dosing and contraindications?

Tenecteplase for Massive Pulmonary Embolism: FDA Status and Clinical Use

Tenecteplase is NOT FDA-approved for pulmonary embolism, but is widely used off-label for massive PE with hemodynamic instability based on strong guideline support from the American Heart Association, American College of Cardiology, and European Society of Cardiology. 1

FDA Approval Status

• Tenecteplase currently lacks FDA approval for pulmonary embolism treatment—it is approved only for acute myocardial infarction 1
• Despite the absence of formal FDA approval, major cardiology societies recommend tenecteplase as an acceptable alternative to alteplase (which IS FDA-approved at 100 mg over 2 hours for massive PE) 1, 2

Clinical Indications for Off-Label Use

Tenecteplase is recommended specifically for high-risk (massive) pulmonary embolism, defined as:

• Sustained hypotension (systolic BP <90 mmHg for ≥15 minutes) 1
• Cardiogenic shock requiring vasopressor support 1
• Cardiac arrest or pulselessness 1
• Persistent profound bradycardia (HR <40 bpm) with signs of shock 1

The mortality benefit of thrombolysis in this population is clearly established, with untreated massive PE carrying a 52-65% mortality rate 2

Weight-Based Dosing Protocol (Off-Label)

The American Heart Association and American College of Cardiology recommend the standard STEMI dosing regimen, administered as a single IV bolus over 5 seconds: 1, 3

• <60 kg: 30 mg 1, 3
• 60-69 kg: 35 mg 1, 3
• 70-79 kg: 40 mg 1, 3
• 80-89 kg: 45 mg 1, 3
• ≥90 kg: 50 mg 1, 3

This single-bolus approach offers practical advantages over alteplase's 2-hour infusion protocol 3

Administration Protocol

• Give tenecteplase as a single IV bolus over 5 seconds via peripheral IV 1
• Administer before or concurrent with anticoagulation (unfractionated heparin or LMWH) 1
• Expect rapid hemodynamic improvement, with 92% of patients showing clinical and echocarographic improvement within 36 hours 1

Anticoagulation Management

• Heparin should be stopped before administering tenecteplase 3
• Resume heparin at maintenance dosing after thrombolysis is complete, targeting aPTT 1.5-2.5 times control 3
• For catheter-directed therapy, low-dose UFH (5-10 U/kg/hour) may be used concurrently 2

Absolute Contraindications

The American Heart Association and American College of Cardiology identify the following absolute contraindications: 1

• Prior intracranial hemorrhage (any time) 1
• Known structural cerebral vascular lesion (AVM, aneurysm) 1
• Known malignant intracranial neoplasm 1
• Acute ischemic stroke within the previous 6 months 1
• Recent significant head trauma or intracranial/intraspinal surgery 1
• Active internal bleeding 1

Critical caveat: In life-threatening massive PE with hemodynamic collapse or cardiac arrest, most traditional contraindications become relative and may need to be overridden given the 52-65% mortality without treatment 1, 2, 3

Bleeding Risk Profile

• Major bleeding occurs in approximately 13% of patients 1
• Intracranial hemorrhage risk is 1.8-2% 1
• Elderly patients (>75 years) have significantly higher bleeding risk and may require dose reduction 1
• Recent observational data suggest tenecteplase may carry higher bleeding rates than alteplase in massive PE (17% vs 5% in one 2025 study), though mortality outcomes appear similar 4

Special Populations and Dosing Considerations

• Elderly patients (>75 years): Consider dose reduction due to significantly elevated ICH risk, though specific reduced-dose protocols lack robust validation 1
• Reduced-dose protocols: Do NOT use "half-dose" tenecteplase outside of research protocols—this is not guideline-supported 3
• One 2025 case report described successful use of 0.37 mg/kg (17.5 mg) in a patient >90 years old, but this remains investigational 5

Critical Clinical Pitfalls to Avoid

• Do NOT delay tenecteplase in massive PE with hemodynamic collapse while awaiting imaging confirmation—clinical diagnosis plus bedside echo showing RV dysfunction is sufficient when cardiac arrest is imminent 1, 3
• Do NOT use tenecteplase routinely in intermediate-risk PE without careful risk-benefit assessment, given the 2% stroke risk 1
• Do NOT use reduced or "half-dose" tenecteplase outside of research protocols 3
• Do NOT re-administer tenecteplase if re-occlusion occurs, as this may lead to excessive bleeding complications 1

Evidence Quality and Comparative Data

• The weight-based tenecteplase dosing is extrapolated from STEMI trials rather than PE-specific randomized controlled trials 3
• A 2024 multicenter registry study (283 matched pairs) found similar 30-day mortality between tenecteplase and alteplase (19.4% vs 19.8%) 6
• A 2025 prospective observational study found no difference in mortality (80% vs 86.2%), major bleeding (8.0% vs 6.9%), or ROSC achievement (22.2% vs 28.6%) between tenecteplase and alteplase 7
• However, a 2025 retrospective cohort raised concern about potentially higher bleeding rates with tenecteplase (17% vs 5%), though the study was limited by small sample size (n=44) 4

Alternative Thrombolytic Options

If tenecteplase is unavailable or contraindicated, acceptable alternatives include:

• Alteplase 100 mg over 2 hours (FDA-approved for massive PE) 1, 2
• Alteplase 50 mg IV bolus for cardiac arrest or rapidly deteriorating patients 2
• Catheter-directed thrombolysis when systemic thrombolysis is contraindicated, with 87% procedural success rate 1
• Surgical embolectomy for absolute contraindications to thrombolysis or failed thrombolytic therapy 1, 2