What is the administration window and protocol for Tenecteplase (TNK) in acute ischemic stroke?

Tenecteplase (TNK) Administration Window and Protocol for Acute Ischemic Stroke

Tenecteplase should be administered as a single IV bolus at a dose of 0.25 mg/kg (maximum 25 mg) within 4.5 hours of stroke symptom onset. 1

Dosing and Administration

• Tenecteplase is administered as a single IV weight-based bolus at 0.25 mg/kg with a maximum dose of 25 mg 1
• Unlike alteplase which requires a bolus followed by an hour-long infusion, tenecteplase is given as a single bolus due to its longer half-life (90-130 minutes) 1, 2
• Treatment should be initiated as soon as possible after patient arrival and CT scan, with efforts to minimize door-to-needle times 1
• The single-bolus administration offers significant workflow advantages, particularly in centers considering endovascular therapy or patient transfer 1, 2

Time Window

• The standard treatment window for tenecteplase in acute ischemic stroke is within 4.5 hours of symptom onset 1, 3
• Recent research (TIMELESS trial) showed no benefit of tenecteplase when administered 4.5 to 24 hours after stroke onset, even in patients with salvageable tissue on perfusion imaging 4
• Treatment should be initiated as early as possible within this window, as efficacy decreases with time 1

Clinical Evidence and Guidelines

• 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) 5, 2
• The 0.25 mg/kg dose is specifically recommended for large vessel occlusions based on trials demonstrating superior recanalization compared to alteplase 1
• 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 3
• Network meta-analyses suggest that 0.25 mg/kg may be the optimal dose of tenecteplase for patients with acute ischemic stroke, with the best balance of efficacy and safety 6, 7

Contraindications

• Absolute contraindications include: 8

  • Any prior intracranial hemorrhage
  • Known structural cerebral vascular lesion (e.g., arteriovenous malformation)
  • Known malignant intracranial neoplasm (primary or metastatic)
  • Ischemic stroke within 3 months
  • Suspected aortic dissection
  • Significant closed-head or facial trauma within 3 months

• Relative contraindications include: 8

  • History of chronic, severe, poorly controlled hypertension
  • Significant hypertension on presentation (SBP >180 mm Hg or DBP >110 mm Hg)
  • History of prior ischemic stroke >3 months
  • Dementia
  • Major surgery (<3 weeks)
  • Recent internal bleeding (within 2-4 weeks)
  • Noncompressible vascular punctures
  • Pregnancy
  • Active peptic ulcer
  • Current use of oral anticoagulant therapy

Safety Considerations

• Tenecteplase appears to have a similar safety profile to alteplase 3, 6
• Higher doses of tenecteplase (0.40 mg/kg) have not shown improved efficacy over the 0.25 mg/kg dose and may increase the risk of symptomatic intracranial hemorrhage 9, 7
• In elderly patients, tenecteplase 0.25 mg/kg may have a lower rate of symptomatic intracranial hemorrhage compared to alteplase 0.9 mg/kg 7

Comparison to Other Thrombolytics

• Tenecteplase and alteplase are the only recommended fibrinolytic agents for acute ischemic stroke 5
• The benefit of other IV fibrinolytic agents is unproven and not recommended outside clinical trials 5
• Streptokinase should not be used due to unacceptably high rates of hemorrhage 5