What is the recommended dosage of tenecteplase (TNK-tPA) for acute ischemic stroke?

Tenecteplase Dosage in Acute Ischemic Stroke

The recommended dosage of tenecteplase for acute ischemic stroke is 0.25 mg/kg (maximum 25 mg) administered as a single intravenous bolus within 4.5 hours of symptom onset. 1

Dosing Rationale and Evidence

Tenecteplase at 0.25 mg/kg provides the optimal balance of efficacy and safety for acute ischemic stroke treatment. This dosage has been extensively evaluated and is supported by the most recent clinical guidelines and research:

• The 0.25 mg/kg dose (maximum 25 mg) is specifically recommended by the American College of Cardiology and the American Heart Association for acute ischemic stroke 1
• This dose has demonstrated higher rates of arterial recanalization when given prior to mechanical thrombectomy compared to alteplase 1, 2
• The EXTEND-IA TNK study showed superior reperfusion rates with tenecteplase 0.25 mg/kg compared to alteplase (22% vs 10% substantial reperfusion) 1, 2

Administration Protocol

Tenecteplase should be administered as follows:

• Single IV bolus (not an infusion like alteplase)
• Must be given within 4.5 hours of symptom onset
• Administer as quickly as possible after the decision to perform thrombolysis
• For patients requiring mechanical thrombectomy, immediate transfer to a comprehensive stroke center should follow administration 1

Clinical Advantages of Tenecteplase

Tenecteplase offers several advantages over alteplase:

• Higher fibrin specificity
• Longer half-life
• Single-bolus administration (versus continuous infusion)
• Better safety profile with comparable efficacy 1
• Lower rates of symptomatic intracranial hemorrhage in recent analyses 1
• Lower mortality at 30 days (8.2% vs 9.8% with alteplase) 1

Patient Selection

Tenecteplase at 0.25 mg/kg is particularly beneficial for:

• Patients requiring urgent transport to comprehensive stroke centers
• Patients eligible for mechanical thrombectomy
• Patients with large vessel occlusion 1

Contraindications

Absolute contraindications include:

• Previous intracranial hemorrhage
• Known structural cerebral vascular lesion
• Known malignant intracranial neoplasm
• Ischemic stroke within the last 3 months
• Suspected aortic dissection
• Active bleeding or hemorrhagic diathesis
• Significant head or facial trauma within the last 3 months
• Intracranial or intraspinal surgery within the last 2 months
• Severe uncontrolled hypertension (SBP >180 mmHg or DBP >110 mmHg) 1

Clinical Evidence Supporting 0.25 mg/kg Dosage

Multiple studies have evaluated different tenecteplase doses:

• Early dose-escalation studies tested doses from 0.1 to 0.5 mg/kg, with doses of 0.1 to 0.4 mg/kg found to be safe 3
• The 0.5 mg/kg dose was associated with increased symptomatic intracranial hemorrhage (15% of patients) 3
• A systematic review and meta-analysis of randomized controlled trials concluded that 0.25 mg/kg is the optimal dose, offering better rates of early neurological recovery without increased safety concerns 4
• The ORIGINAL trial (2024) confirmed the noninferiority of tenecteplase 0.25 mg/kg to alteplase with respect to excellent functional outcomes at 90 days with a similar safety profile 5

Common Pitfalls to Avoid

• Exceeding the maximum dose: Never exceed the maximum dose of 25 mg, regardless of patient weight
• Delayed administration: Efficacy decreases with time; administer as soon as possible within the 4.5-hour window
• Using in contraindicated patients: Carefully screen for all contraindications before administration
• Incorrect dosing: Using higher doses (0.5 mg/kg) has been associated with increased risk of symptomatic intracranial hemorrhage 3
• Failure to arrange immediate transfer: For patients with large vessel occlusion, immediate transfer for potential mechanical thrombectomy is essential after tenecteplase administration 1

In conclusion, tenecteplase at 0.25 mg/kg (maximum 25 mg) as a single IV bolus is the recommended dose for acute ischemic stroke treatment within 4.5 hours of symptom onset, offering an effective alternative to alteplase with practical advantages of single-bolus administration and a favorable safety profile.