What is the recommended dose of Tenecteplase (TNK-tPA) for a patient with acute ischemic stroke?

Tenecteplase Dosing for Acute Ischemic Stroke

For acute ischemic stroke, administer tenecteplase as a single intravenous bolus at 0.25 mg/kg (maximum dose 25 mg) within 4.5 hours of symptom onset. 1, 2

Weight-Based Dosing Protocol

The specific weight-based dosing for tenecteplase in stroke differs from its myocardial infarction dosing—clinicians must not confuse these protocols: 3

• <60 kg: 30 mg 4
• 60-69 kg: 35 mg 4
• 70-79 kg: 40 mg 4
• 80-89 kg: 45 mg 4
• ≥90 kg: 50 mg (maximum dose) 4

Critical distinction: The stroke dose is 0.25 mg/kg (max 25 mg), while the MI dose is 0.5 mg/kg—using the wrong protocol could result in overdosing. 3

Administration Advantages

Tenecteplase offers significant practical advantages over alteplase due to its longer half-life (90-130 minutes): 1, 2

• Single bolus administration eliminates the need for the 1-hour infusion required with alteplase 3
• Reduces nursing time and potential medication errors 3
• Particularly advantageous in centers performing endovascular therapy or requiring patient transfer 1, 2

Timing and Workflow

Treatment must be initiated as soon as possible after CT scan confirms eligibility: 1

• Target door-to-needle time <60 minutes in 90% of patients 3
• Administer within 4.5 hours of symptom onset 1, 5
• Even if endovascular therapy is planned, eligible patients should still receive IV thrombolysis first 3

Evidence Supporting 0.25 mg/kg Dose

The 0.25 mg/kg dose is specifically recommended based on robust evidence: 1

• ORIGINAL trial (2024): Demonstrated noninferiority to alteplase with 72.7% achieving mRS 0-1 at 90 days versus 70.3% with alteplase 6
• EXTEND-IA TNK Part 2 (2020): Showed no advantage of 0.40 mg/kg over 0.25 mg/kg for reperfusion (19.3% vs 19.3%), with numerically higher symptomatic ICH at the higher dose (4.7% vs 1.3%) 7
• Dose-escalation studies identified 0.5 mg/kg as unsafe (15% symptomatic ICH rate), while 0.1-0.4 mg/kg were safe 8

Guideline Status

The American Heart Association/American Stroke Association suggests tenecteplase might be considered as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion (Class IIb, Level of Evidence B-R). 1, 3

For large vessel occlusions specifically, the 0.25 mg/kg dose demonstrates superior recanalization rates (22% vs 10% with alteplase) and improved 3-month outcomes. 3, 9

Safety Profile

Tenecteplase shares similar contraindications with alteplase: 1, 2

Absolute contraindications: 4

• Any prior intracranial hemorrhage
• Known structural cerebral vascular lesion
• Known malignant intracranial neoplasm
• Ischemic stroke within 3 months (except acute ischemic stroke within 4.5 hours)
• Suspected aortic dissection
• Active bleeding or bleeding diathesis
• Significant closed-head or facial trauma within 3 months
• Severe uncontrolled hypertension (SBP >180 or DBP >110 mm Hg)

Relative contraindications: 4

• Recent internal bleeding (within 2-4 weeks)
• Noncompressible vascular punctures
• Pregnancy
• Active peptic ulcer
• Current oral anticoagulant therapy

The symptomatic intracranial hemorrhage risk is approximately 6% (number needed to harm = 17), balanced against a number needed to treat of 8-14 for favorable outcomes. 3, 2