What should be the gap between 2 tPA (tissue Plasminogen Activator) doses?

Recommended Gap Between TNK (Tenecteplase) Doses

For reteplase (rPA), two 10-unit IV boluses should be administered 30 minutes apart, while for tenecteplase (TNK-tPA), a single IV weight-based bolus is the recommended administration method with no need for a second dose. 1

Administration Protocols for Different tPA Formulations

Tenecteplase (TNK-tPA)

• Administered as a single IV weight-based bolus 1:
  • 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

Reteplase (rPA)

• Administered as two 10-unit IV boluses given 30 minutes apart (each administered over 2 minutes) 1

Alteplase (tPA)

• Administered as a 90-minute weight-based infusion 1:
  • Adults ≥67 kg: 100-mg total dosage as 15-mg IV bolus, followed by 50-mg IV over 30 min, then 35-mg IV over 60 min
  • Adults <67 kg: 15-mg IV bolus, followed by 0.75 mg/kg IV (≤50 mg) over 30 min, then 0.5 mg/kg IV (≤35 mg) over 60 min

Clinical Applications of tPA Formulations

For Acute Myocardial Infarction

Tenecteplase is preferred over non-fibrin-specific agents due to:

• Higher specificity for fibrin
• Superior patency rates
• Less immunogenicity
• Reduced non-cerebral bleeding compared to alteplase 1

For Pleural Infection

When using tPA plus DNase for pleural infection:

• Standard regimen: 10 mg tPA twice daily + 5 mg DNase twice daily for 3 days 1
• Alternative lower-dose regimen: 5 mg tPA twice daily + 5 mg DNase twice daily for 3 days 1

For Acute Ischemic Stroke

• Alteplase is administered at 0.9 mg/kg (maximum 90 mg) with 10% given as IV bolus over 1 minute and remaining 90% as IV infusion over 60 minutes 2
• The therapeutic window for IV alteplase is within 4.5 hours of symptom onset 2

For Catheter Clearance

• For catheter dysfunction due to thrombosis, tPA is administered at a lumen fill volume and allowed to dwell for 1 hour or longer 1

Important Considerations

Safety Profile

• Tenecteplase has demonstrated a favorable safety profile with lower rates of intracranial hemorrhage compared to alteplase, even at the highest weight-optimized dosage of 50 mg 3
• Recent meta-analyses show tenecteplase 0.25 mg/kg is superior to alteplase for excellent functional outcomes in acute ischemic stroke while maintaining similar safety profiles 4

Pharmacokinetics

• Tenecteplase has a prolonged half-life (17 ± 7 minutes) compared to wild-type tPA (3.5 ± 1.4 minutes) 5
• This extended half-life allows for single-bolus administration rather than requiring multiple doses 5

Common Pitfalls to Avoid

1. Using the wrong dosing protocol for the specific indication (stroke vs. myocardial infarction vs. catheter clearance)
2. Administering a second dose of tenecteplase when it's designed as a single-dose agent
3. Confusing the administration protocols between different tPA formulations
4. Not adjusting doses based on patient weight when indicated
5. Not considering contraindications such as recent surgery, bleeding disorders, or uncontrolled hypertension 1, 2

Remember that tenecteplase is administered as a single bolus with no need for a second dose, while reteplase requires two boluses 30 minutes apart, and alteplase is given as a 90-minute infusion.