What is the appropriate weight‑based dosing of tenecteplase for acute ST‑segment‑elevation myocardial infarction (or pulmonary embolism), including maximum dose, contraindications, and any required dose adjustments?

Tenecteplase Dosing for STEMI and Pulmonary Embolism

For acute ST-elevation myocardial infarction (STEMI), administer tenecteplase as a single intravenous bolus over 5 seconds using weight-tiered dosing: 30 mg for <60 kg, 35 mg for 60–69 kg, 40 mg for 70–79 kg, 45 mg for 80–89 kg, and 50 mg (maximum) for ≥90 kg. 1

Weight-Based Dosing Table for STEMI

Patient Weight	Tenecteplase Dose	Volume (mL)*
<60 kg	30 mg	6
60–69 kg	35 mg	7
70–79 kg	40 mg	8
80–89 kg	45 mg	9
≥90 kg	50 mg (maximum)	10

*From one vial reconstituted with 10 mL Sterile Water for Injection 1

This weight-tiered approach approximates 0.5 mg/kg with a ceiling dose of 50 mg, endorsed by both the American College of Cardiology and European Society of Cardiology. 2, 3, 4

Administration Technique

• Reconstitute the 50 mg vial with exactly 10 mL of the supplied Sterile Water for Injection (final concentration 5 mg/mL). 1
• Gently swirl until dissolved; do NOT shake. 1
• Draw up the appropriate volume based on weight tier from the table above. 1
• Administer as a single rapid intravenous bolus over 5 seconds (not as an infusion). 2, 1
• Flush any dextrose-containing IV lines with 0.9% sodium chloride before and after administration, as tenecteplase precipitates with dextrose. 1

Dose Adjustments and Special Populations

Obesity (BMI ≥30)

The maximum dose remains capped at 50 mg regardless of weight above 90 kg. 5, 1 The 2024 European Society of Cardiology consensus on antithrombotic therapy in obesity confirms this ceiling dose for STEMI, noting that patients >90 kg receive 50 mg without further dose escalation. 5

Elderly Patients (≥75 years)

• For STEMI: Use the standard weight-tiered tenecteplase dosing without reduction. 3, 4
• For stroke: If using tenecteplase off-label for acute ischemic stroke, the dose is 0.25 mg/kg (maximum 25 mg), with some guidelines suggesting half-dosing in patients >75 years. 5

Renal Dysfunction

No specific dose adjustment for tenecteplase itself is required in renal impairment. 1 However, avoid enoxaparin as ancillary anticoagulation if creatinine >2.5 mg/dL (men) or >2.0 mg/dL (women); use unfractionated heparin instead. 5, 4

Mandatory Ancillary Anticoagulation for STEMI

All patients receiving tenecteplase for STEMI require concurrent anticoagulation:

Age <75 Years with Normal Renal Function

• Enoxaparin: 30 mg IV bolus (given with or immediately after tenecteplase), then 1 mg/kg subcutaneously every 12 hours. 5, 3, 4

Age ≥75 Years OR Renal Dysfunction

• Unfractionated heparin: 60 U/kg IV bolus (maximum 4000 U), followed by 12 U/kg/hour infusion (maximum 1000 U/hour), targeting aPTT 1.5–2.0 times control (50–70 seconds). 5, 1

Additional Antiplatelet Therapy

• Aspirin: 150–325 mg oral loading dose (or 80–150 mg IV if unable to take orally), then 75–100 mg daily. 3, 4
• Clopidogrel: 300 mg loading dose for patients ≤75 years; for patients >75 years, start with 75 mg daily without loading dose. 3

Timing Considerations

Administer tenecteplase immediately after STEMI diagnosis when primary percutaneous coronary intervention (PCI) cannot be performed within 120 minutes of first medical contact. 2, 4 The greatest mortality benefit occurs when given within 12 hours of symptom onset, with maximal benefit in the first 2 hours. 3, 4

Pulmonary Embolism Dosing

For hemodynamically stable patients with acute pulmonary embolism and right ventricular dysfunction, the same weight-adjusted STEMI dosing regimen (30–50 mg based on weight tiers) has been studied and is feasible. 6 However, this remains an off-label indication in most jurisdictions, as FDA approval is limited to STEMI. 1

For massive pulmonary embolism with hemodynamic instability, alteplase 100 mg over 2 hours remains the standard FDA-approved regimen, though tenecteplase at STEMI doses has been used in clinical practice. 5

Absolute Contraindications

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

• Active internal bleeding
• History of cerebrovascular accident (any prior intracranial hemorrhage)
• Intracranial or intraspinal surgery or trauma within 2 months
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Known bleeding diathesis
• Severe uncontrolled hypertension (systolic >180 mmHg or diastolic >110 mmHg)

Critical Pitfalls to Avoid

• Never use the STEMI dose (0.5 mg/kg) for stroke. The stroke dose is 0.25 mg/kg (maximum 25 mg), and confusing these doses can cause fatal intracranial hemorrhage. 2
• Do not delay administration to obtain precise weight. Use estimated weight to select the appropriate tier; the tiered system accommodates reasonable estimates. 2
• Do not administer as an infusion. Tenecteplase must be given as a rapid 5-second bolus. 1
• Do not cap the dose below 50 mg in obese patients. Underdosing in patients >90 kg reduces the likelihood of achieving arterial patency. 5
• Flush dextrose lines before and after. Precipitation occurs when tenecteplase contacts dextrose solutions. 1

Post-Administration Monitoring

Monitor ST-segment resolution, cardiac rhythm, and symptoms at 60–90 minutes after administration. 5, 4 Successful reperfusion is indicated by:

• Relief of chest pain
• Hemodynamic and electrical stability
• ≥50% reduction in ST-segment elevation on follow-up ECG 5, 4

Transfer all patients to a PCI-capable center following fibrinolysis. 4 Perform rescue PCI immediately if fibrinolysis fails (<50% ST-segment resolution at 60 minutes). 4

Pharmacokinetic Rationale

Tenecteplase has an initial half-life of 17–24 minutes and terminal half-life of 65–132 minutes, approximately 4-fold slower clearance than alteplase. 7, 8 This prolonged half-life permits single-bolus administration. 7 Body weight explains 19% of clearance variability, with each 10 kg increase in weight resulting in 9.6 mL/min increased clearance, supporting the weight-adjusted dosing strategy. 7