What is the recommended time frame for administering tenecteplase (generic name: tenecteplase) in cerebral infarction after the onset of stroke symptoms?

Tenecteplase Administration Timeframe for Cerebral Infarction

Tenecteplase should be administered within 4.5 hours of stroke symptom onset in patients with acute ischemic stroke. 1, 2

Evidence-Based Timeframe Guidelines

The administration of tenecteplase for cerebral infarction follows specific time-based protocols:

Within 3 Hours (Strongest Evidence)

• Class I, Level of Evidence A recommendation for administration within 3 hours of symptom onset 1
• Highest benefit-to-risk ratio is achieved when administered as early as possible
• Treatment should be initiated as quickly as possible as the benefit is strongly time-dependent 1

3-4.5 Hour Window

• Class I, Level of Evidence B-R recommendation for selected patients who can be treated within 3 to 4.5 hours 1
• Patients ≤80 years of age without history of both diabetes mellitus and prior stroke
• NIHSS score ≤25
• Not taking oral anticoagulants
• No imaging evidence of ischemic injury involving more than one-third of the MCA territory 1

Dosing and Administration

• Recommended dose: 0.25 mg/kg (maximum 25 mg) as a single IV bolus 2, 3
• Tenecteplase offers advantages over alteplase:
  • Higher fibrin specificity
  • Longer half-life
  • Single bolus administration (versus 60-minute infusion for alteplase)
  • Better safety profile with comparable efficacy 2

Patient Selection Considerations

Eligibility Criteria

• Measurable neurological deficit
• No evidence of intracranial hemorrhage on CT
• Blood pressure <185/110 mmHg
• No recent history of major surgery, trauma, or bleeding
• Not taking oral anticoagulants or INR <1.7 if taking warfarin 1

Contraindications

• Any prior intracranial hemorrhage
• Known structural cerebral vascular lesion
• Known malignant intracranial neoplasm
• Ischemic stroke within 3 months
• 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 2

Important Clinical Considerations

Beyond 4.5 Hours

• Recent evidence from the TRACE-III trial suggests potential benefit of tenecteplase in selected patients with large vessel occlusion and salvageable brain tissue on perfusion imaging between 4.5-24 hours 4
• However, the TIMELESS trial showed no benefit of tenecteplase between 4.5-24 hours in patients who mostly underwent thrombectomy 5
• Current guidelines do not recommend routine use beyond 4.5 hours outside of clinical trials or specialized centers with advanced imaging capabilities

Special Situations

• For wake-up strokes with unknown onset time, tenecteplase is not recommended if the time last known to be at baseline state is >4.5 hours 1
• Patients with large vessel occlusion may benefit from tenecteplase prior to mechanical thrombectomy when administered within 4.5 hours 3

Implementation Considerations

• Door-to-needle time goals should be established with a primary goal of achieving treatment within 60 minutes in ≥50% of patients 1
• A secondary goal of door-to-needle times within 45 minutes in ≥50% of patients may be reasonable 1
• Multicomponent quality improvement initiatives are recommended to safely increase thrombolytic treatment rates 1

Conclusion

The evidence strongly supports administering tenecteplase within 4.5 hours of stroke symptom onset, with the greatest benefit observed within the first 3 hours. Treatment should be initiated as quickly as possible after symptom onset, as the effectiveness of therapy is highly time-dependent.