What is the recommended dosing regimen for Tenecteplase (TNK)?

Tenecteplase (TNK) Dosing Regimen

The recommended dosing regimen for Tenecteplase (TNK) is a single intravenous weight-based bolus administered over 5 seconds as follows: 30 mg for weight <60 kg, 35 mg for 60-69 kg, 40 mg for 70-79 kg, 45 mg for 80-89 kg, and 50 mg for ≥90 kg. 1, 2

Weight-Based Dosing Protocol

Patient Weight (kg)	TNKase Dose (mg)	Volume to be administered (mL)
< 60	30	6
60 to < 70	35	7
70 to < 80	40	8
80 to < 90	45	9
≥ 90	50	10

Administration Guidelines

1. Preparation:

   • Use a sterile syringe to withdraw 10 mL of Sterile Water for Injection
   • Reconstitute the TNKase vial with the 10 mL diluent to obtain a 5 mg/mL concentration
   • Gently swirl until completely dissolved (do not shake)
   • The solution should be colorless to pale yellow and transparent

2. Administration:

   • Administer as a single IV bolus over 5 seconds
   • Flush dextrose-containing IV lines with 0.9% sodium chloride before and after administration (TNKase is incompatible with dextrose solutions) 2

Clinical Context and Timing

• Initiate treatment as soon as possible after onset of STEMI symptoms
• Greatest benefit occurs within the first 12 hours after symptom onset 1
• May be considered in symptomatic patients presenting >12 hours after symptom onset with a large area of myocardium at risk or hemodynamic instability when PCI is unavailable 1

Adjunctive Therapy

When administering TNKase, the following adjunctive therapies should be provided:

1. Antiplatelet therapy:

   • Aspirin: 162-325 mg loading dose, followed by daily maintenance
   • Clopidogrel: 300 mg loading dose for patients <75 years of age, 75 mg for patients ≥75 years 1, 3

2. Anticoagulation:

   • Unfractionated heparin (UFH): 60 U/kg IV bolus (maximum 4000 U) followed by 12 U/kg/hr infusion (maximum 1000 U/hr), adjusted to maintain aPTT at 1.5-2.0 times control (approximately 50-70 seconds) 1
   • Alternatively, enoxaparin may be used in patients <75 years without significant renal dysfunction 1

Special Considerations

1. Elderly patients:

   • Consider half-dose for patients >75 years old to reduce the risk of intracranial hemorrhage 3

2. Post-fibrinolysis care:

   • Transfer to a PCI-capable center immediately after fibrinolytic therapy 1
   • Early angiography between 2 and 24 hours with intent to perform PCI is recommended to reduce rates of death or MI 1

Contraindications

Absolute Contraindications:

• Any prior intracranial hemorrhage
• Known structural cerebral vascular lesion
• Known malignant intracranial neoplasm
• 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) 1, 2

Relative Contraindications:

• History of chronic, severe, poorly controlled hypertension
• Significant hypertension on presentation
• History of prior ischemic stroke >3 months
• Dementia
• Known intracranial pathology not covered in absolute contraindications
• Traumatic or prolonged CPR
• Major surgery (<3 weeks)
• Recent internal bleeding
• Noncompressible vascular punctures
• Pregnancy
• Active peptic ulcer 1

Clinical Advantages of TNKase

Tenecteplase has higher fibrin specificity compared to other thrombolytic agents and offers several advantages:

• Single bolus administration (vs. 90-minute infusion for alteplase)
• Equivalent 30-day mortality rates compared to alteplase
• Reduced non-cerebral bleeding compared to alteplase 1
• No procoagulant effects compared to streptokinase or rt-PA 4

This weight-based dosing regimen was developed based on extensive clinical research showing that higher doses per unit body weight result in faster culprit artery flow, which may reflect earlier opening, reduced stunning, or improved microvascular function 5, 6.