When is Tenecteplase (TNK) indicated, what are the weight‑based bolus doses for ST‑segment‑elevation myocardial infarction (STEMI) and acute ischemic stroke, and what are the absolute contraindications?

Tenecteplase (TNK) Indications, Dosing, and Contraindications

Tenecteplase is indicated for ST-segment elevation myocardial infarction (STEMI) when administered within 12 hours of symptom onset as a weight-based single bolus, and may be considered for acute ischemic stroke at 0.25 mg/kg within 4.5 hours, though it remains off-label for stroke in many jurisdictions. 1, 2, 3

Indications

STEMI

• TNK is indicated for STEMI patients presenting within 12 hours of symptom onset when primary percutaneous coronary intervention (PCI) cannot be performed within 120 minutes of first medical contact 1, 2
• A fibrin-specific agent (tenecteplase, alteplase, or reteplase) is the recommended class of thrombolytic for STEMI 4
• Use beyond 12 hours may be considered only in specific circumstances: symptomatic patients with large areas of myocardium at risk or hemodynamic instability when PCI is unavailable 1

Acute Ischemic Stroke

• TNK at 0.25 mg/kg may be considered as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion, though it has not been proven superior or noninferior to alteplase 4
• The 0.25 mg/kg dose within 4.5 hours of symptom onset has been shown to be consistently effective and safe 3
• TNK demonstrated superiority over alteplase in achieving >50% reperfusion (22% vs 10%) and better 90-day functional outcomes when given before thrombectomy 5

Weight-Based Dosing

STEMI Dosing

• 30 mg for patients <60 kg 6
• 35 mg for patients 60-69 kg 6
• 40 mg for patients 70-79 kg 6
• 45 mg for patients 80-89 kg 6
• 50 mg for patients ≥90 kg (maximum dose 0.53 mg/kg) 6
• Administered as a single intravenous bolus over 5-10 seconds 7, 6

Acute Ischemic Stroke Dosing

• 0.25 mg/kg (maximum 25 mg) as a single bolus within 4.5 hours of symptom onset 3, 5, 8
• This dose demonstrated the greatest odds of achieving 90-day excellent independence (mRS ≤1) compared to alteplase without increased risk of symptomatic intracerebral hemorrhage 8
• The 0.4 mg/kg dose showed increased odds of symptomatic intracerebral hemorrhage and is not recommended 4, 8

Absolute Contraindications

The following are absolute contraindications that preclude TNK administration under any circumstances:

• Any prior intracranial hemorrhage at any time in the patient's history 1
• Known structural cerebral vascular lesion (arteriovenous malformation, aneurysm) 1
• Known malignant intracranial neoplasm (primary or metastatic brain tumor) 1
• Ischemic stroke within the past 3 months 1
• Suspected aortic dissection 1
• Significant closed-head or facial trauma within 3 months 1

Relative Contraindications

These require careful risk-benefit assessment but are not absolute prohibitions:

Cardiovascular and Vascular

• Significant hypertension on presentation (SBP >180 mmHg or DBP >110 mmHg) 1
• History of chronic, severe, poorly controlled hypertension 1
• Traumatic or prolonged cardiopulmonary resuscitation (>10 minutes) 1
• Noncompressible vascular punctures 1

Neurological

• History of ischemic stroke >3 months ago 1
• Dementia 1
• Known intracranial pathology not covered in absolute contraindications 1

Bleeding Risk

• Major surgery within 3 weeks 1
• Recent internal bleeding (within 2-4 weeks) 1
• Active peptic ulcer disease 1
• Current use of oral anticoagulant therapy 1

Other

• Pregnancy 1

Adjunctive Therapy for STEMI

When TNK is used for STEMI, the following must be administered:

• Aspirin (oral or IV) 4
• Clopidogrel in addition to aspirin 4
• Anticoagulation with enoxaparin IV followed by subcutaneous (preferred) or weight-adjusted unfractionated heparin bolus followed by infusion, continued until revascularization or for hospital stay up to 8 days 4, 2
• Transfer to PCI-capable center immediately after fibrinolysis in all patients 4, 2

Post-Fibrinolysis Management

Critical monitoring and intervention steps:

• Assess ST-segment resolution at 60-90 minutes post-TNK administration 2
• Perform rescue PCI immediately if <50% ST-segment resolution or if hemodynamic/electrical instability or worsening ischemia occurs 4, 2
• Perform angiography and PCI of infarct-related artery between 2-24 hours after successful fibrinolysis (≥50% ST-segment resolution) 4, 2
• Emergency angiography indicated for heart failure, cardiogenic shock, or recurrent ischemia 4, 2

Practical Advantages

TNK offers significant logistical benefits over alteplase:

• Single bolus administration over 5-10 seconds versus 90-minute infusion for alteplase 7, 6
• Longer half-life (17-24 minutes initial phase) allows sustained thrombolytic activity 6
• 80-fold reduced binding to plasminogen activator inhibitor PAI-1 6
• 15-fold higher fibrin specificity enables more targeted clot dissolution 3, 6
• Potential for decreased medication errors and improved door-to-thrombolytic time 7