According to the 2026 AHA/ASA stroke guideline, what are the indications, dosing regimen, and recommendation class for tenecteplase in acute ischemic stroke?

Tenecteplase for Acute Ischemic Stroke: Dosing, Indications, and Recommendations

Primary Recommendation

For patients with acute ischemic stroke presenting within 4.5 hours of symptom onset who are eligible for intravenous thrombolysis, tenecteplase 0.25 mg/kg (maximum 25 mg) administered as a single intravenous bolus over 5-10 seconds is recommended as a safe and effective alternative to alteplase, particularly in patients with large vessel occlusion. 1, 2, 3

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Dosing Regimen

• Standard dose: 0.25 mg/kg administered as a single IV bolus over 5-10 seconds, with a maximum dose of 25 mg 1, 2
• Critical dosing distinction: The stroke dose (0.25 mg/kg, max 25 mg) differs from the STEMI dose (0.5 mg/kg, max 50 mg)—clinicians must not confuse these protocols 4, 2
• No infusion pump required: The entire dose is delivered as a rapid bolus, eliminating the 60-minute infusion required for alteplase 1, 4
• Weight estimation acceptable: Precise weight measurement is not mandatory; estimated weight can be used to avoid treatment delays 2

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Indications and Recommendation Class

Strong Recommendations (Class I Equivalent)

• Large vessel occlusion (LVO) within 4.5 hours: Tenecteplase 0.25 mg/kg is recommended over alteplase 0.9 mg/kg for patients with LVO acute ischemic stroke eligible for IVT (moderate evidence, strong recommendation) 3
• General acute ischemic stroke <4.5 hours: Tenecteplase 0.25 mg/kg can be used as a safe and effective alternative to alteplase 0.9 mg/kg (moderate evidence, strong recommendation) 3

Weaker Recommendations (Class IIb)

• Minor neurological impairment without major intracranial occlusion: The American Heart Association/American Stroke Association suggests tenecteplase might be considered as an alternative to alteplase (Class IIb, Level of Evidence B-R) 1, 4
• Prehospital mobile stroke unit management: Tenecteplase 0.25 mg/kg is suggested over alteplase 0.90 mg/kg (low evidence, weak recommendation) 3

Strong Recommendations Against

• Tenecteplase 0.40 mg/kg dose: Not recommended for any acute ischemic stroke patients (low evidence, strong recommendation) 3, 5
• Wake-up stroke or unknown onset selected with non-contrast CT: Tenecteplase 0.25 mg/kg is not recommended (low evidence, strong recommendation) 3

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Time Window and Treatment Urgency

• Treatment window: Up to 4.5 hours from symptom onset or last known well 1, 2, 3
• Door-to-needle time: Treatment should be initiated as soon as possible after CT scan, with target door-to-needle time <60 minutes in 90% of patients 4, 2
• Time-dependent benefit: Every effort should be made to minimize delays, as time to treatment is strongly associated with outcomes 6

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Contraindications (Shared with Alteplase)

Absolute Contraindications

• Evidence of intracranial hemorrhage on CT 4, 2
• Recent significant trauma or surgery within 3 months 6, 4
• Uncontrolled hypertension (>185/110 mm Hg) 4, 2
• Unclear or unwitnessed symptom onset with time last known well >4.5 hours 6
• Prior ischemic stroke within 3 months 6

Relative Contraindications

• Recent internal bleeding within 2-4 weeks 1
• Noncompressible vascular punctures 1
• Pregnancy 1
• Active peptic ulcer 1
• Current use of oral anticoagulant therapy (requires careful assessment) 1

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Clinical Advantages Over Alteplase

• Single-bolus administration: Tenecteplase's longer half-life (90-130 minutes) allows single-bolus delivery versus alteplase's 60-minute infusion 1, 4
• Workflow benefits: Particularly advantageous in centers considering endovascular therapy or patient transfer 1, 4
• Reduced medication errors: Simplified administration reduces nursing time and potential infusion-related errors 4, 2
• Superior recanalization in LVO: Achieves higher reperfusion rates (22% vs 10% substantial reperfusion) before mechanical thrombectomy 4, 7

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Integration with Endovascular Therapy

• Do not delay thrombectomy: Patients should proceed directly to mechanical thrombectomy without waiting to observe clinical response after tenecteplase administration—delaying worsens outcomes 2
• Combined therapy preferred: For basilar artery occlusion, combined IVT and endovascular therapy is suggested over direct endovascular therapy when IVT is not contraindicated 6
• Patients eligible for IVT should receive it: Even if endovascular therapies are being considered, eligible patients should receive IV thrombolysis (Class I, Level of Evidence A) 4

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Critical Pitfalls to Avoid

• Wrong dose for indication: Never use the STEMI dose (0.5 mg/kg) for stroke; only 0.25 mg/kg is evidence-based 6, 4, 2
• Do not administer as infusion: Tenecteplase must be given as a rapid bolus, not diluted for infusion over time 2
• Avoid higher doses: The 0.40 mg/kg dose has inferior outcomes and is not recommended 3, 5
• Blood pressure control: Ensure BP can be safely lowered to <185/110 mm Hg before administration 6
• Imaging requirements: CT must exclude intracranial hemorrhage and extensive hypoattenuation (frank hypodensity representing irreversible injury) 6

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Evidence Quality and Nuances

• Non-inferiority established: Multiple randomized controlled trials demonstrate tenecteplase 0.25 mg/kg is non-inferior to alteplase for functional outcomes at 90 days 3, 5
• Potential superiority in LVO: The European Stroke Organisation provides a strong recommendation for tenecteplase over alteplase specifically in large vessel occlusion cases based on moderate-quality evidence 3
• Comparable safety profile: No significant difference in symptomatic intracranial hemorrhage rates between tenecteplase 0.25 mg/kg and alteplase 3, 5
• Dose-response relationship: Subgroup analyses demonstrate 0.25 mg/kg is more beneficial than 0.40 mg/kg doses 5