What is the dose of tenecteplase (tissue plasminogen activator) for acute ischemic stroke?

Tenecteplase Dosing for Acute Ischemic Stroke

For acute ischemic stroke, tenecteplase should be administered as a single intravenous weight-based bolus at a dose of 0.25 mg/kg (maximum 25 mg). 1, 2

Dosing Guidelines

• Tenecteplase is administered as a single IV weight-based bolus, with the following dosing recommendations 3:

  • 30 mg for weight <60 kg
  • 35 mg for 60-69 kg
  • 40 mg for 70-79 kg
  • 45 mg for 80-89 kg
  • 50 mg for ≥90 kg

• However, for acute ischemic stroke specifically, clinical evidence supports using a lower dose of 0.25 mg/kg (maximum 25 mg) 1, 2

Advantages Over Alteplase

• Tenecteplase has higher fibrin specificity and a longer half-life (90-130 minutes) compared to alteplase, allowing for single-bolus administration rather than the 1-hour infusion required for alteplase 1, 4
• The single-bolus administration offers significant workflow advantages, particularly in centers considering endovascular therapy or patient transfer 1
• Tenecteplase has demonstrated noninferiority to alteplase with respect to excellent functional outcomes at 90 days with a similar safety profile 5
• In patients with large vessel occlusions, tenecteplase has shown superior recanalization rates compared to alteplase 4, 2

Safety Considerations

• Dose-escalation studies have established that tenecteplase doses of 0.1 to 0.4 mg/kg are safe in ischemic stroke 6
• Higher doses (0.4 mg/kg and above) have been associated with increased rates of symptomatic intracranial hemorrhage 7, 6
• The 0.25 mg/kg dose has emerged as the optimal balance between efficacy and safety 4, 2

Time Window for Administration

• Tenecteplase should be administered within 4.5 hours of stroke symptom onset, similar to the time window for alteplase 5, 2
• The American Heart Association/American Stroke Association recommends tenecteplase as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion 1

Contraindications

• Contraindications for tenecteplase are similar to those for alteplase, including 1:
  • Any prior intracranial hemorrhage
  • Known structural cerebral vascular lesions
  • Known malignant intracranial neoplasms
  • Ischemic stroke within 3 months (except acute ischemic stroke within 4.5 hours)
  • Suspected aortic dissection
  • Active bleeding or bleeding diathesis
  • Significant closed-head or facial trauma within 3 months
  • Intracranial or intraspinal surgery within 2 months
  • Severe uncontrolled hypertension (SBP >180 mm Hg or DBP >110 mm Hg)

Clinical Evidence

• 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 5
• The EXTEND-IA TNK trial showed that tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcomes than alteplase among patients with ischemic stroke treated within 4.5 hours 2