What is the dosage and administration of tenecteplase for acute ischemic stroke and pulmonary embolism?

Tenecteplase Dosing and Administration

Acute Ischemic Stroke

For acute ischemic stroke, administer tenecteplase as a single intravenous bolus at 0.25 mg/kg (maximum dose 25 mg) within 4.5 hours of symptom onset. 1, 2

Weight-Based Dosing Protocol

• <60 kg: 30 mg 1
• 60-69 kg: 35 mg 1
• ≥70 kg: Calculate 0.25 mg/kg, maximum 25 mg 2

Administration Details

• Single bolus injection over 5-10 seconds—this is a critical advantage over alteplase's 1-hour infusion 1, 2
• Initiate immediately after CT scan confirms no hemorrhage, with every effort to minimize door-to-needle times 2
• The longer half-life (90-130 minutes) eliminates the need for infusion pumps and continuous monitoring 1, 2

Clinical Evidence Supporting This Dose

• The ORIGINAL trial (2024) demonstrated noninferiority of tenecteplase 0.25 mg/kg versus alteplase 0.9 mg/kg, with 72.7% achieving excellent functional outcomes (mRS 0-1) at 90 days 3
• Meta-analyses suggest the 0.25 mg/kg dose is superior to 0.4 mg/kg with better efficacy and lower hemorrhage risk 4
• For large vessel occlusions specifically, the 0.25 mg/kg dose demonstrates superior recanalization and improved 3-month outcomes compared to alteplase 2, 5

Guideline Recommendations

• The American Heart Association/American Stroke Association considers tenecteplase as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion (Class IIb, Level B-R) 1, 2
• Patients eligible for IV thrombolysis should receive treatment even if endovascular therapy is planned (Class I, Level A) 1

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Pulmonary Embolism

For acute pulmonary embolism, tenecteplase is administered as an intravenous bolus, though specific dosing is not standardized in current guidelines. 6

Clinical Context

• The 2014 ESC Guidelines tested tenecteplase against placebo in intermediate-risk PE patients 6
• Tenecteplase showed fewer adverse outcomes, better functional capacity, and greater quality of life at 3 months when added to LMWH 6
• However, the PEITHO trial revealed significant safety concerns: 2% hemorrhagic stroke rate (versus 0.2% placebo) and 6.3% major non-intracranial bleeding (versus 1.5% placebo) 6

Critical Safety Considerations

• Accelerated regimens over 2 hours are preferable to prolonged 12-24 hour infusions of first-generation agents 6
• Greatest benefit occurs when initiated within 48 hours of symptom onset, though may be useful up to 6-14 days 6
• Increasing age and comorbidities significantly elevate bleeding risk 6

Important Caveats

• The ESC guidelines reference "approved regimens" in Web Addenda Table III, but specific tenecteplase dosing for PE is not detailed in the provided evidence 6
• Consider reduced-dose strategies or catheter-directed approaches in patients at high bleeding risk 6
• Thrombolysis should be reserved for high-risk or selected intermediate-high-risk PE given the hemorrhage risks 6

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Contraindications (Both Indications)

Absolute Contraindications

• Evidence of intracranial hemorrhage on imaging 2
• Recent significant trauma or surgery 2
• Uncontrolled hypertension 2

Relative Contraindications

• Recent internal bleeding (within 2-4 weeks) 2
• Noncompressible vascular punctures 2
• Pregnancy 2
• Active peptic ulcer 2
• Current oral anticoagulant therapy 2

Special Warning: Do Not Use Before Primary PCI

• The ASSENT 4 PCI trial was terminated early due to higher mortality when tenecteplase was given before planned primary PCI for STEMI 7
• This principle may apply to stroke patients being transferred for thrombectomy, though the single-bolus administration actually facilitates transfer logistics 1, 2