What are the recommended dosing, administration, and contraindications for tenecteplase in adults with acute ST‑segment‑elevation myocardial infarction?

Tenecteplase for Acute STEMI

Tenecteplase should be administered as a single weight-based IV bolus over 5 seconds when primary PCI cannot be achieved within 2 hours of first medical contact in patients with STEMI presenting within 12 hours of symptom onset and no contraindications to fibrinolysis. 1, 2

Dosing

Weight-tiered single IV bolus administered over 5 seconds 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

Special population: For patients ≥75 years, consider half-dose tenecteplase 3

The 2025 ACC/AHA guidelines prioritize tenecteplase among fibrin-specific agents due to its single-bolus administration advantage over alteplase (90-minute infusion) and reteplase (two boluses 30 minutes apart) 1. The weight-based dosing optimizes the patency-to-bleeding relationship across patient weights 2.

Administration Timing

Initiate within 10 minutes of STEMI diagnosis 1, 3

The decision algorithm is straightforward:

• If primary PCI achievable within 2 hours of first medical contact: Transfer for primary PCI
• If primary PCI NOT achievable within 2 hours AND symptoms <12 hours: Administer fibrinolytic therapy immediately 1, 3
• Preferably in pre-hospital setting if trained personnel available 3

The benefit is time-dependent with greatest mortality reduction when administered early, especially within first 2 hours of symptom onset 1, 3. For patients presenting >12 hours after symptom onset, fibrinolysis is generally not indicated unless there is ongoing ischemia with large area of myocardium at risk or hemodynamic instability 1.

Absolute Contraindications 1, 2

• Any prior intracranial hemorrhage
• Known structural cerebral vascular lesion (arteriovenous malformation)
• Known malignant intracranial neoplasm (primary or metastatic)
• Ischemic stroke within 3 months (except acute ischemic stroke within 4.5 hours)
• Suspected aortic dissection
• Active internal bleeding or bleeding diathesis (excluding menses)
• Significant closed-head or facial trauma within 3 months
• Intracranial or intraspinal surgery within 2 months
• Severe uncontrolled hypertension unresponsive to therapy (SBP >180 mmHg or DBP >110 mmHg)

Relative Contraindications 1

• History of chronic, severe, poorly controlled hypertension
• Significant hypertension on presentation (SBP >180 mmHg or DBP >110 mmHg)
• History of prior ischemic stroke >3 months
• Dementia
• Traumatic or prolonged CPR (>10 minutes)
• Major surgery within 3 weeks
• Recent internal bleeding (within 2-4 weeks)
• Noncompressible vascular punctures
• Pregnancy
• Active peptic ulcer
• Oral anticoagulant therapy

Mandatory Adjunctive Therapy

Antiplatelet therapy 3:

• Aspirin: Oral or IV loading dose immediately
• Clopidogrel: Loading dose plus maintenance (prasugrel/ticagrelor may be considered 48 hours after fibrinolysis if PCI performed) 3

Anticoagulation (until revascularization or up to 8 days) 3:

• Preferred: Enoxaparin IV bolus followed by subcutaneous (superior to UFH) 3
• Alternative: UFH as weight-adjusted IV bolus followed by infusion 3

Post-Fibrinolysis Management

All patients must be transferred immediately to PCI-capable center 1, 3

Assessment for reperfusion success at 60-90 minutes 1, 3:

• Measure ST-segment resolution (<50% in anterior leads or <70% in inferior leads indicates failure)
• Monitor for persistent ischemic symptoms, hemodynamic instability, or electrical instability

Timing of angiography 1, 3:

• Immediate rescue PCI: If failed fibrinolysis (<50% ST-segment resolution), hemodynamic/electrical instability, or worsening ischemia
• Routine angiography: Between 2-24 hours after successful fibrinolysis
• Emergency angiography: Heart failure, cardiogenic shock, or recurrent ischemia/reocclusion

Critical Safety Considerations

Avoid planned primary PCI strategy combined with full-dose tenecteplase. The ASSENT 4 PCI trial was terminated early due to increased mortality (6.7% vs 4.9%) and worse outcomes when tenecteplase was administered prior to planned primary PCI 2. The composite endpoint of death/cardiogenic shock/CHF at 90 days was significantly higher (18.6% vs 13.4%, p=0.0045) 2. Choose either fibrinolysis OR primary PCI as the primary reperfusion strategy—not both simultaneously 1, 2.

Bleeding risk: Tenecteplase increases bleeding risk. Avoid intramuscular injections and noncompressible vascular punctures 2. In comparative trials, tenecteplase showed equivalent intracranial hemorrhage rates to alteplase but fewer noncerebral bleeding complications 1, 4, 5.

Monitor for hypersensitivity reactions during and for several hours after administration 2.