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
Standard Dosing Protocol
- Administer 0.25 mg/kg as a single IV bolus (maximum 25 mg) within 4.5 hours of symptom onset 1, 2
- This single-bolus administration contrasts with alteplase's more complex regimen (10% bolus followed by 1-hour infusion), offering significant workflow advantages particularly when endovascular therapy or patient transfer is being considered 3
- The longer half-life of tenecteplase (90-130 minutes) enables this convenient single-bolus dosing 1, 2
Critical Dosing Caveat
Do not confuse stroke dosing with myocardial infarction dosing—the stroke dose is 0.25 mg/kg (max 25 mg), NOT the 0.5 mg/kg used for MI. 3 This is a common and potentially dangerous error that clinicians must avoid.
Evidence Supporting the 0.25 mg/kg Dose
The 0.25 mg/kg dose is specifically recommended based on:
- Superior recanalization rates in large vessel occlusions compared to alteplase 1
- Improved 3-month functional outcomes relative to alteplase in patients with large vessel occlusions 1
- The ORIGINAL trial demonstrated noninferiority to alteplase for excellent functional outcomes (mRS 0-1 at 90 days) with similar safety profile 4
- Meta-analyses of 1,585 randomized patients support noninferiority in disability-free outcomes without increased symptomatic intracranial hemorrhage 5
Why Not Higher Doses?
Avoid the 0.4 mg/kg dose in moderate to severe stroke—pooled analysis from the NOR-TEST trials showed this higher dose resulted in:
- Worse functional outcomes (OR 0.52 for favorable outcome, p=0.003) 6
- Significantly higher mortality (OR 2.48, p=0.01) 6
- Increased rates of intracranial hemorrhage, particularly in severe strokes 6
The 0.25 mg/kg dose has emerged as the optimal balance of efficacy and safety 7, 5
Clinical Context and Patient Selection
The American Heart Association/American Stroke Association suggests tenecteplase as an alternative to alteplase (Class IIb, Level of Evidence B-R) in patients with:
- Minor neurological impairment and no major intracranial occlusion 1, 3
- However, the 0.25 mg/kg dose shows particular advantage in large vessel occlusions where superior recanalization has been demonstrated 1
Administration Timing
- Initiate treatment as soon as possible after CT scan 1
- Target door-to-needle time <60 minutes in 90% of treated patients 3
- Patients eligible for IV thrombolysis should receive it even if endovascular therapy is being considered (Class I, Level of Evidence A) 2
Contraindications
Both tenecteplase and alteplase share similar contraindications:
- Evidence of intracranial hemorrhage 1, 2
- Recent significant trauma or surgery 1, 2
- Uncontrolled hypertension 1, 2
- Recent internal bleeding (within 2-4 weeks), noncompressible vascular punctures, pregnancy, active peptic ulcer, and current oral anticoagulant use are relative contraindications 1, 2