What is the appropriate tenecteplase (TNK) dose for an adult with ST‑elevation myocardial infarction based on weight?

Tenecteplase (TNK) Dosing for STEMI

Tenecteplase is administered as a single intravenous weight-based bolus over 5 seconds, with doses ranging from 30 mg for patients <60 kg to 50 mg for patients ≥90 kg. 1, 2

Weight-Based Dosing Regimen

The dosing is strictly weight-adjusted as follows: 1, 2

• <60 kg: 30 mg (6 mL)
• 60-69 kg: 35 mg (7 mL)
• 70-79 kg: 40 mg (8 mL)
• 80-89 kg: 45 mg (9 mL)
• ≥90 kg: 50 mg (10 mL)

This weight-based approach is critical because pharmacokinetic studies demonstrate that a 10 kg increase in body weight results in a 9.6 mL/min increase in drug clearance, and weight explains 19% of the variability in clearance. 3 Plasma exposure correlates directly with achieving TIMI 3 flow—more than 75% of patients achieve normal coronary flow when their plasma concentration exceeds 3.6 mcg/mL. 3

Preparation and Administration

Reconstitute the lyophilized powder with exactly 10 mL of Sterile Water for Injection (supplied) to achieve a final concentration of 5 mg/mL. 2 Gently swirl—do not shake—and allow large bubbles to dissipate by standing undisturbed for several minutes. 2

Flush any dextrose-containing IV lines with 0.9% sodium chloride before and after TNK administration, as precipitation occurs when TNK contacts dextrose. 2 Administer the calculated dose as a single IV bolus over 5 seconds directly into an IV port. 2

If not used immediately after reconstitution, refrigerate at 2-8°C and use within 8 hours. 2

Timing Considerations

Initiate TNK as soon as possible after symptom onset, ideally within the first 2 hours when benefit is maximal. 1 Fibrinolytic therapy is indicated when primary PCI cannot be performed within 120 minutes of first medical contact. 1 Benefits extend up to 12 hours after symptom onset, though efficacy diminishes with time. 1

For patients presenting 12-24 hours after symptom onset with ongoing ischemia and a large area of myocardium at risk or hemodynamic instability, fibrinolysis may still be considered if PCI is unavailable. 1

Mandatory Adjunctive Therapy

All patients receiving TNK must receive aspirin and anticoagulation. 1

Antiplatelet Therapy:

• Aspirin: 150-325 mg orally (chewable, non-enteric coated) or 250-500 mg IV if oral not possible, then 75-100 mg daily. 1
• Clopidogrel:
  • Age ≤75 years: 300 mg loading dose, then 75 mg daily 1
  • Age >75 years: No loading dose—start with 75 mg daily 1

Anticoagulation:

Enoxaparin is preferred over unfractionated heparin. 1

• Age <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneous every 12 hours 1
• Age ≥75 years: No IV bolus—start with 0.75 mg/kg subcutaneous every 12 hours 1

If enoxaparin unavailable, use unfractionated heparin: 60 U/kg IV bolus (maximum 4000 U) followed by 12 U/kg/hour infusion (maximum 1000 U/hour) for 24-48 hours. 1

Continue anticoagulation until revascularization or hospital discharge (up to 8 days). 1

Absolute Contraindications

Do not administer TNK if any of the following are present: 1

• Any prior intracranial hemorrhage
• Known structural cerebral vascular lesion (e.g., arteriovenous malformation)
• Known malignant intracranial neoplasm (primary or metastatic)
• Ischemic stroke within 3 months (except acute ischemic stroke within 4.5 hours)
• Suspected aortic dissection
• Active bleeding or bleeding diathesis (excluding menses)
• 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 unresponsive to therapy)

Post-Fibrinolytic Management

Transfer all patients to a PCI-capable center following fibrinolysis. 1 Perform angiography and PCI of the infarct-related artery between 2-24 hours after successful fibrinolysis in stable patients. 1

Immediate emergency angiography and PCI is indicated if fibrinolysis fails, defined as <50% ST-segment resolution at 60-90 minutes after TNK administration. 1

Critical Pitfalls to Avoid

Accurate weight measurement is essential—underdosing due to estimated weight reduces efficacy, as plasma concentrations directly correlate with achieving coronary patency. 3, 4 The pharmacokinetic data show that weight-adjusted dosing optimizes the therapeutic regimen. 4

Never mix TNK with dextrose-containing solutions—this causes precipitation and loss of drug activity. 2 Always flush lines with normal saline before and after administration.

Do not delay administration for non-absolute contraindications—relative contraindications (e.g., recent surgery <3 weeks, pregnancy, active peptic ulcer) require clinical judgment weighing ischemic risk against bleeding risk, but should not automatically preclude therapy when myocardial salvage is substantial. 1

Unlike streptokinase, TNK can be re-administered if clinically indicated, as it is not antigenic. 1