What is the recommended Tenecteplase dosing regimen for an adult acute ischemic stroke presenting within 4.5 hours of symptom onset with no contraindications to thrombolysis?

Tenecteplase Dosing for Acute Ischemic Stroke

For adults with acute ischemic stroke presenting within 4.5 hours of symptom onset, administer tenecteplase 0.25 mg/kg (maximum 25 mg) as a single intravenous bolus over 5-10 seconds. 1, 2

Evidence Basis and Regulatory Status

The American Heart Association/American Stroke Association assigns tenecteplase a Class IIb, Level B-R recommendation as an alternative to alteplase for patients with minor neurological impairment and no major intracranial occlusion. 3, 2 However, the most recent high-quality trials demonstrate that tenecteplase 0.25 mg/kg is non-inferior to alteplase across the full spectrum of stroke severity within 4.5 hours. 4, 5

Key Trial Evidence Supporting 0.25 mg/kg Dosing:

• ATTEST-2 (2024): In 1,777 UK patients treated within 4.5 hours, tenecteplase 0.25 mg/kg was non-inferior to alteplase 0.9 mg/kg for 90-day functional outcomes (OR 1.07,95% CI 0.90-1.27), with similar safety profiles including symptomatic ICH rates of 2% in both groups. 4

• ORIGINAL (2024): In 1,465 Chinese patients, tenecteplase 0.25 mg/kg achieved excellent outcomes (mRS 0-1) in 72.7% versus 70.3% with alteplase (RR 1.03,95% CI 0.97-1.09), meeting non-inferiority with identical symptomatic ICH rates of 1.2%. 5

Administration Protocol

Pre-Treatment Requirements:

• Blood pressure must be <185/110 mmHg before administering tenecteplase; treat hypertension aggressively to achieve this target. 2
• Non-contrast CT or MRI must exclude intracranial hemorrhage. 1, 6
• Blood glucose must be >50 mg/dL. 1

Dosing Calculation:

• Calculate 0.25 mg/kg of actual body weight (not ideal body weight). 1, 2
• Maximum dose is 25 mg regardless of weight. 1, 2
• Administer as a single IV bolus over 5-10 seconds—this is the key practical advantage over alteplase's 60-minute infusion. 1, 2

Post-Administration Monitoring:

• Neurological assessments every 15 minutes during and immediately after bolus, then every 30 minutes for 6 hours. 2
• Blood pressure monitoring: every 15 minutes for 2 hours, then every 30 minutes for 6 hours, then hourly to 24 hours. 2
• Maintain BP ≤180/105 mmHg for at least 24 hours post-treatment. 2
• If severe headache, acute hypertension, nausea, or vomiting occur, obtain emergent CT immediately. 2

Time Window Considerations

0-3 Hour Window:

• Tenecteplase may be offered to all eligible patients meeting NINDS criteria, including those >80 years old and with severe strokes (NIHSS >25). 2

3-4.5 Hour Window (ECASS III Criteria):

• Additional exclusions apply: age >80 years, any oral anticoagulant use (regardless of INR), NIHSS >25, or combined history of diabetes and prior stroke. 1, 2

Beyond 4.5 Hours:

• Do not use tenecteplase beyond 4.5 hours outside of clinical trials. The TIMELESS trial (2024) showed no benefit when tenecteplase was given 4.5-24 hours after onset, even with perfusion imaging selection. 7
• Observational data beyond 4.5 hours show higher intracranial hemorrhage rates with tenecteplase compared to alteplase without improved outcomes. 8

Absolute Contraindications

• Prior intracranial hemorrhage at any time. 1, 2
• Ischemic stroke or severe head trauma within 3 months. 1, 2
• Intracranial or spinal surgery within 3 months. 1
• Active internal bleeding. 1
• Uncontrolled BP >185/110 mmHg despite treatment. 1, 2
• Platelet count <100,000/mm³ or INR >1.7. 1
• Blood glucose <50 mg/dL. 1

Clinical Decision-Making Algorithm

Step 1: Confirm stroke onset or last known well time is <4.5 hours. 1, 2

Step 2: Obtain immediate non-contrast CT to exclude hemorrhage. 1, 6

Step 3: Verify BP <185/110 mmHg and glucose >50 mg/dL. 1, 2

Step 4: If 0-3 hours from onset, proceed with tenecteplase for all eligible patients regardless of age or stroke severity. 2

Step 5: If 3-4.5 hours from onset, exclude patients >80 years, on any oral anticoagulant, NIHSS >25, or with both diabetes and prior stroke. 1, 2

Step 6: Administer 0.25 mg/kg (max 25 mg) as single IV bolus over 5-10 seconds. 1, 2

Step 7: If large vessel occlusion suspected (NIHSS ≥6, cortical signs), proceed immediately to endovascular thrombectomy evaluation—do not wait to assess tenecteplase response. 6

Practical Advantages Over Alteplase

• Single-bolus administration eliminates the need for infusion pumps and 60-minute monitoring, facilitating pre-hospital use and interhospital transfers. 1, 4
• Longer half-life (90-130 minutes) provides sustained thrombolytic activity. 2
• Greater fibrin specificity may reduce systemic bleeding risk. 9
• The ATTEST-2 investigators concluded that "easier administration of tenecteplase, especially in the context of interhospital transfers, indicates that tenecteplase should be preferred to alteplase for thrombolysis in acute ischemic stroke." 4

Common Pitfalls to Avoid

• Do not use the 0.4 mg/kg dose studied in earlier trials; the 0.25 mg/kg dose has the strongest evidence for non-inferiority and safety. 3, 4, 5
• Do not delay tenecteplase to obtain CTA or assess for thrombectomy eligibility—administer thrombolysis first, then proceed with imaging and endovascular evaluation. 6
• Do not withhold tenecteplase from patients with minor but disabling deficits (e.g., isolated aphasia, hand weakness)—these can cause substantial functional loss. 1
• Do not use tenecteplase beyond 4.5 hours even with perfusion imaging—recent trial data show no benefit and potential harm. 7, 8