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

Tenecteplase Dosing for Acute Ischemic Stroke

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

Dosing Guidelines

• Tenecteplase is administered as a single IV weight-based bolus at 0.25 mg/kg (maximum dose of 25 mg) for acute ischemic stroke 1
• Unlike alteplase, tenecteplase is given as a single bolus rather than an infusion due to its longer half-life (90-130 minutes) 1, 2
• The single-bolus administration offers significant workflow advantages, particularly in centers considering endovascular therapy or patient transfer 1, 3

Evidence Supporting the 0.25 mg/kg Dose

• 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) 4, 1
• The 0.25 mg/kg dose is specifically recommended for large vessel occlusions based on trials demonstrating superior recanalization and improved 3-month outcomes relative to alteplase 1, 2
• Recent meta-analyses indicate that tenecteplase 0.25 mg/kg is superior to alteplase 0.9 mg/kg in achieving excellent functional outcomes (OR, 1.16; 95% CrI, 1.01-1.33) 5
• The ORIGINAL trial demonstrated that tenecteplase at 0.25 mg/kg was noninferior to alteplase with respect to excellent functional outcomes (mRS score of 0 or 1) at 90 days 6

Higher Dose Considerations

• While a 0.4 mg/kg dose has been studied, evidence does not suggest an advantage of this higher dose over the 0.25 mg/kg dose 2
• In network meta-analyses, tenecteplase 0.25 mg/kg ranked first in efficacy outcomes while tenecteplase 0.4 mg/kg ranked last 5
• The EXTEND-IA TNK Part 2 trial was designed to compare 0.25 mg/kg versus 0.4 mg/kg tenecteplase, but results did not demonstrate clear superiority of the higher dose 7

Safety Profile

• Tenecteplase has a safety profile similar to alteplase with respect to symptomatic intracerebral hemorrhage 6, 5, 8
• In the ORIGINAL trial, symptomatic intracerebral hemorrhage occurred in 1.2% of patients in both the tenecteplase and alteplase groups 6
• Both tenecteplase and alteplase share similar contraindications, including evidence of intracranial hemorrhage, recent significant trauma or surgery, and uncontrolled hypertension 1, 3

Clinical Implementation

• Treatment with tenecteplase should be initiated as soon as possible after patient arrival and CT scan, with every effort made to minimize door-to-needle times 1
• The single-bolus administration of tenecteplase (versus the 1-hour infusion required for alteplase) may improve workflow in acute stroke management 1, 3

Caution

• The benefit of IV fibrinolytic agents other than alteplase and tenecteplase is unproven; therefore, their administration is not recommended outside a clinical trial 4
• While tenecteplase is approved for use in myocardial infarction at a dose of 0.5 mg/kg, this higher dose is not recommended for stroke treatment 2