Tenecteplase (TNK) for Acute Ischemic Stroke
Tenecteplase is now a suitable alternative to alteplase for acute ischemic stroke treatment within 4.5 hours of symptom onset, with the advantage of single-bolus administration and superior recanalization rates, particularly in patients with large vessel occlusion. 1, 2
Key Pharmacologic Advantages
Tenecteplase offers significant practical benefits over alteplase:
- Single-bolus administration (0.25 mg/kg, maximum 25 mg) versus alteplase's 1-hour infusion protocol, reducing nursing time and medication errors 1, 3
- Longer half-life (90-130 minutes) compared to alteplase, allowing for simplified dosing 1
- Greater fibrin specificity with reduced systemic coagulopathy 4, 5
- Superior recanalization rates (22% vs 10% substantial reperfusion) prior to mechanical thrombectomy 1
Weight-Based Dosing Protocol
Administer tenecteplase as a single IV bolus using the following weight-based dosing 1:
- <60 kg: 30 mg
- 60-69 kg: 35 mg
- ≥70 kg: Standard 0.25 mg/kg (maximum 25 mg)
For comparison, alteplase requires 0.9 mg/kg (maximum 90 mg) with 10% as initial bolus over 1 minute, then 90% infused over 60 minutes 3
Clinical Efficacy Evidence
The highest quality recent evidence demonstrates noninferiority to alteplase:
- ORIGINAL trial (2024): Tenecteplase achieved 72.7% excellent functional outcomes (mRS 0-1) versus 70.3% with alteplase, meeting noninferiority criteria 2
- Meta-analysis of 5 trials: TNK showed 57.9% disability-free outcomes versus 55.4% with alteplase, with the lower confidence interval well within noninferiority margins 6
- Recanalization superiority: TNK demonstrates higher recanalization rates without increasing intracerebral hemorrhage risk 5, 7
Guideline Recommendations and Time Windows
Current guidelines support tenecteplase use with specific considerations:
- Within 3 hours: Both agents are strongly recommended (Level A evidence) 3
- 3-4.5 hours: Both agents are conditionally recommended for carefully selected patients (Level B evidence) 3
- AHA/ASA position: Tenecteplase may be considered as an alternative to alteplase, particularly in patients with minor neurological impairment and no major intracranial occlusion (Class IIb, Level B-R) 1
Critical caveat: Even if endovascular therapy is planned, eligible patients should still receive IV thrombolysis without delay 1
Blood Pressure Requirements
Identical strict blood pressure criteria apply to both agents 3:
Pre-treatment (absolute contraindication if not met):
- SBP must be <185 mmHg
- DBP must be <110 mmHg
Post-treatment targets for 24 hours:
- SBP ≤180 mmHg
- DBP ≤105 mmHg
Monitoring frequency 3:
- Every 15 minutes for first 2 hours
- Every 30 minutes for hours 2-8
- Hourly from hours 8-24
Safety Profile
Both agents share similar safety profiles:
- Symptomatic ICH rate: 1.2% for both tenecteplase and alteplase in head-to-head comparison 2
- 90-day mortality: 4.6% with tenecteplase versus 5.8% with alteplase 2
- Shared contraindications: Prior intracranial hemorrhage, recent significant trauma/surgery, uncontrolled hypertension 1
Practical Clinical Advantages
Tenecteplase offers workflow benefits that make it particularly attractive:
- Faster administration in centers considering endovascular therapy or patient transfer 1
- Reduced complexity eliminates infusion pump setup and monitoring 1
- Lower risk of dosing errors with single-bolus administration 1
Agents to Avoid
Never use streptokinase due to unacceptably high hemorrhage rates 1. Other agents (reteplase, urokinase, anistreplase) lack extensive stroke testing and are not recommended 1.
Post-Thrombolytic Management
Regardless of agent chosen 3:
- Admit to ICU or stroke unit for minimum 24 hours intensive monitoring
- Neurological assessments every 15 minutes during/immediately after administration
- Every 30 minutes for 6 hours post-treatment
- Hourly from hours 6-24
If symptomatic ICH suspected: Immediately discontinue infusion, obtain emergent CT, consider cryoprecipitate for fibrinogen replacement, and obtain neurosurgical consultation 3