Tenecteplase: Comprehensive Clinical Overview
Mechanism and Pharmacology
Tenecteplase is a genetically engineered variant of alteplase with superior fibrin specificity and a significantly longer half-life (90-130 minutes), enabling single-bolus administration rather than the 1-hour infusion required for alteplase. 1, 2
- The enhanced fibrin specificity allows for more targeted clot dissolution with potentially reduced systemic bleeding complications 3, 4
- The extended half-life eliminates the need for continuous infusion, offering substantial workflow advantages particularly in centers performing endovascular therapy or patient transfers 1, 2
Acute Ischemic Stroke
Dosing and Administration
For acute ischemic stroke, tenecteplase should be administered as a single intravenous bolus at 0.25 mg/kg (maximum dose 25 mg) within 4.5 hours of symptom onset. 2, 1
- Weight-based dosing: 30 mg for <60 kg, 35 mg for 60-69 kg 1
- Critical warning: The stroke dosing (0.25 mg/kg, max 25 mg) differs from myocardial infarction dosing (0.5 mg/kg)—clinicians must not confuse these protocols 1
- Treatment should be initiated as soon as possible after CT scan, targeting door-to-needle time <60 minutes in 90% of patients 1, 2
Guideline Recommendations
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). 1, 2
- For the 0-3 hour window: IV thrombolysis should be offered to patients meeting NINDS inclusion/exclusion criteria 1
- For the 3-4.5 hour window: IV thrombolysis should be considered in patients meeting ECASS III criteria 1
- Patients eligible for IV thrombolysis should receive it even if endovascular therapies are being considered (Class I, Level of Evidence A) 1
Clinical Efficacy
The ORIGINAL trial demonstrated that tenecteplase 0.25 mg/kg was noninferior to alteplase, with 72.7% achieving excellent functional outcomes (mRS 0-1) at 90 days versus 70.3% with alteplase. 5, 1
- For large vessel occlusions prior to mechanical thrombectomy, tenecteplase achieves superior reperfusion rates (22% vs 10% substantial reperfusion with alteplase) 1
- The EXTEND-IA TNK trial demonstrated higher reperfusion rates, though not powered for clinical outcomes 1
- Greater reperfusion (74% vs 44%) and major vessel recanalization rates have been observed with tenecteplase 6
Safety Profile
Both tenecteplase and alteplase share similar contraindications including intracranial hemorrhage, recent significant trauma or surgery, and uncontrolled hypertension. 1, 2
- The absolute increase in symptomatic intracranial hemorrhage risk with thrombolysis is approximately 6% (7% with thrombolysis vs 1% without), yielding a number needed to harm of 17 1
- In the ORIGINAL trial, symptomatic intracerebral hemorrhage occurred in 1.2% of patients in both tenecteplase and alteplase groups 5
- 90-day mortality was 4.6% with tenecteplase versus 5.8% with alteplase 5
Relative Contraindications
- Recent internal bleeding (within 2-4 weeks) 2
- Noncompressible vascular punctures 2
- Pregnancy 2
- Active peptic ulcer 2
- Current use of oral anticoagulant therapy (requires careful consideration with novel oral anticoagulants where reliable assays and clinical history are critical) 1, 2
Shared Decision-Making
Discussions should include the number needed to treat of 8-14 for favorable outcomes balanced against the number needed to harm of 17 for symptomatic intracranial hemorrhage. 1
Agents NOT Recommended
Streptokinase should never be used due to unacceptably high hemorrhage rates, and other agents (reteplase, urokinase, anistreplase) lack extensive testing in stroke and are not recommended. 1, 2
Acute Pulmonary Embolism
Role in PE Management
Thrombolytic treatment with tenecteplase restores pulmonary perfusion more rapidly than anticoagulation alone, leading to prompt reduction in pulmonary artery pressure and resistance with concomitant improvement in right ventricular function. 7
- Tenecteplase was tested against placebo in patients with intermediate-risk PE 7
- Over 90% of patients respond favorably to thrombolysis, as judged by clinical and echocardiographic improvement within 36 hours 7
- Greatest benefit occurs when treatment is initiated within 48 hours of symptom onset, though thrombolysis can still be useful in patients symptomatic for 6-14 days 7
Clinical Evidence in PE
In intermediate-risk PE, patients treated with tenecteplase plus LMWH had fewer adverse outcomes, better functional capacity, and greater quality of life at 3 months compared to LMWH alone. 7
Safety Concerns in PE
The PEITHO trial showed a 2% incidence of hemorrhagic stroke after tenecteplase treatment (versus 0.2% in placebo) in patients with intermediate-high-risk PE, with major non-intracranial bleeding events increased to 6.3% versus 1.5% with placebo. 7
- Increasing age and presence of comorbidities are associated with higher risk of bleeding complications 7
- These results underscore the need to improve safety of thrombolytic treatment in patients at increased risk of intracranial or life-threatening bleeding 7
- Reduced-dose rtPA strategies have appeared safe in moderate PE and in patients with hemodynamic instability 7
Administration Preferences
Accelerated regimens administered over 2 hours are preferable to prolonged infusions of first-generation thrombolytic agents over 12-24 hours. 7
Practical Workflow Advantages
The single-bolus administration of tenecteplase reduces nursing time, potential medication errors, and offers significant advantages in centers considering endovascular therapy or patient transfer. 1, 2