What is the recommended dose of tenecteplase (TNK) for acute ischemic stroke?

Recommended Dose of Tenecteplase (TNK) for Acute Ischemic Stroke

The recommended dose of tenecteplase for acute ischemic stroke is 0.25 mg/kg (maximum 25 mg) administered as a single intravenous bolus. 1

Dosing Guidelines

Tenecteplase dosing for acute ischemic stroke differs from the dosing used for myocardial infarction. The evidence supports the following:

• 0.25 mg/kg (maximum 25 mg) is the optimal dose for acute ischemic stroke 1, 2
• This dose provides the best balance of efficacy and safety compared to other doses 2
• Higher doses (0.40 mg/kg) have not shown improved reperfusion rates compared to 0.25 mg/kg but may increase bleeding risk 3
• Lower doses (0.10 mg/kg) may have slightly better safety profiles but potentially reduced efficacy 2, 4

Evidence Supporting This Recommendation

The 0.25 mg/kg dose has consistently demonstrated:

• Comparable efficacy to alteplase (standard 0.9 mg/kg dose) for functional outcomes at 90 days 1, 5
• Better rates of early neurological recovery in some studies 6
• Higher rates of arterial recanalization when given prior to mechanical thrombectomy compared to alteplase 7, 1
• Lower rates of symptomatic intracranial hemorrhage, particularly in elderly patients 1, 2
• Highest Surface Under the Cumulative Ranking (SUCRA) values for both efficacy and safety outcomes 2

Administration Protocol

Tenecteplase should be administered:

• As a single IV bolus (unlike alteplase which requires a bolus followed by infusion)
• Within 4.5 hours of symptom onset 7, 1
• Before mechanical thrombectomy in eligible patients with large vessel occlusion 7, 1

Advantages Over Alteplase

Tenecteplase at 0.25 mg/kg offers several advantages:

• Single bolus administration (versus 60-minute infusion for alteplase)
• Higher fibrin specificity
• Longer half-life
• Comparable or better efficacy
• Similar or improved safety profile
• Logistical advantages for patients requiring transfer to comprehensive stroke centers 1

Contraindications

Absolute contraindications include:

• Any prior intracranial hemorrhage
• Known structural cerebral vascular lesion
• Known malignant intracranial neoplasm
• Ischemic stroke within 3 months (except acute ischemic stroke)
• Suspected aortic dissection
• Active bleeding or bleeding diathesis
• Significant closed-head or facial trauma within 3 months
• Intracranial or intraspinal surgery within 2 months
• Severe uncontrolled hypertension (SBP >180 mm Hg or DBP >110 mm Hg) 7, 1

Special Considerations

• For patients with large vessel occlusion requiring mechanical thrombectomy, tenecteplase at 0.25 mg/kg may be particularly beneficial 1
• Elderly patients may have a significantly lower rate of symptomatic ICH with tenecteplase 0.25 mg/kg compared to alteplase 2
• The 0.40 mg/kg dose should be avoided as it shows no additional benefit in reperfusion but may increase symptomatic ICH risk 3

Clinical Decision Making

When considering thrombolysis for acute ischemic stroke:

1. Confirm patient eligibility (within 4.5 hours of symptom onset, no contraindications)
2. Determine if large vessel occlusion is present (may influence decision for mechanical thrombectomy)
3. Choose tenecteplase 0.25 mg/kg (max 25 mg) as a single IV bolus
4. Arrange immediate transfer to a comprehensive stroke center if mechanical thrombectomy is indicated

The evidence clearly supports tenecteplase 0.25 mg/kg as the optimal dose for acute ischemic stroke, offering comparable efficacy to alteplase with potential advantages in safety profile and ease of administration.