Tenecteplase Dosing for Myocardial Infarction
Tenecteplase should be administered as a single intravenous bolus using weight-based dosing: 30 mg for patients <60 kg, 35 mg for 60-<70 kg, 40 mg for 70-<80 kg, 45 mg for 80-<90 kg, and 50 mg for patients ≥90 kg. 1, 2, 3
Weight-Based Dosing Table
The following weight-tiered dosing regimen is recommended:
| Patient Weight | Tenecteplase Dose | Volume to Administer |
|---|---|---|
| <60 kg | 30 mg | 6 mL |
| 60-<70 kg | 35 mg | 7 mL |
| 70-<80 kg | 40 mg | 8 mL |
| 80-<90 kg | 45 mg | 9 mL |
| ≥90 kg | 50 mg | 10 mL |
Administration Details
Tenecteplase is given as a single intravenous bolus over 5-10 seconds, which represents a major practical advantage over alteplase's 90-minute infusion. 3, 5
The drug should be reconstituted with 10 mL of Sterile Water for Injection to achieve a final concentration of 5 mg/mL. 3
Weight-adjusted dosing is critical because total body weight explains 19% of the variability in plasma clearance—a 10 kg increase in body weight results in a 9.6 mL/min increase in clearance. 6, 7
Timing Requirements
Tenecteplase must be administered within 12 hours of symptom onset, with greatest benefit occurring with earlier administration. 1, 2
The primary indication is when primary PCI cannot be performed by an experienced team within 120 minutes of first medical contact. 8, 1, 2
For patients presenting very early (<2 hours) with large infarcts and low bleeding risk, consider fibrinolysis if time from first medical contact to balloon inflation exceeds 90 minutes. 1, 2, 4
Mandatory Adjunctive Antiplatelet Therapy
Aspirin:
- Loading dose: 150-500 mg orally or 250 mg IV if oral route not possible 1, 2
- Maintenance: 75-100 mg daily indefinitely 1, 4
Clopidogrel:
- Loading dose: 300 mg orally for patients ≤75 years 1, 4
- No loading dose for patients >75 years—start with 75 mg daily 1
- Maintenance: 75 mg daily for minimum 14 days 4
Note that prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis and should not be given. 8
Required Anticoagulation
Enoxaparin (preferred over unfractionated heparin):
Patients <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneous every 12 hours (maximum 100 mg for first two doses) 1, 4
Patients ≥75 years: No IV bolus; start with 0.75 mg/kg subcutaneous every 12 hours (maximum 75 mg for first two doses) 1, 4
Renal impairment (creatinine clearance <30 mL/min): Subcutaneous doses given once every 24 hours regardless of age 1
Duration: Until revascularization or for hospital stay up to 8 days 8, 1, 4
Unfractionated heparin (alternative):
60 U/kg IV bolus (maximum 4000 U) followed by 12 U/kg/hour infusion (maximum 1000 U/hour) for 24-48 hours 1, 4
Target aPTT: 50-70 seconds or 1.5-2.0 times control, monitored at 3,6,12, and 24 hours 1
Careful monitoring is mandatory—aPTT values >70 seconds are associated with higher likelihood of bleeding, reinfarction, and death. 8
Post-Administration Monitoring and Management
Monitor ST-segment elevation, cardiac rhythm, and clinical symptoms over 60-180 minutes after administration. 1, 2
Signs of successful reperfusion include relief of symptoms, hemodynamic/electrical stability, and ≥50% reduction of initial ST-segment elevation on follow-up ECG at 60-90 minutes. 1, 2, 4
All patients must be transferred to a PCI-capable center following fibrinolysis. 8, 1, 2, 4
Rescue PCI is indicated immediately if fibrinolysis fails (<50% ST-segment resolution at 60 minutes). 8, 1, 2
For stable patients after successful fibrinolysis, routine angiography with view to revascularization should occur at 3-24 hours. 1
Pharmacologic Rationale
Tenecteplase has 15-fold higher fibrin specificity, 80-fold reduced binding to PAI-1, and 6-fold prolonged plasma half-life (22 minutes initial, 90-130 minutes terminal) compared to alteplase. 9, 6, 7
The biphasic elimination allows for single bolus administration with mean plasma clearance of 99-119 mL/min across the 30-50 mg dose range. 3, 6, 7
Tenecteplase achieves 85% TIMI 2-3 flow at 90 minutes, with more than 75% of patients achieving normal flow when plasma AUC exceeds 320 μg·min/mL. 4, 6
Clinical Efficacy Evidence
The ASSENT-2 trial (16,949 patients) demonstrated equivalent 30-day mortality between tenecteplase and alteplase (6.2% for both), with similar rates of intracranial hemorrhage (0.9% vs 0.9%) and stroke (1.8% vs 1.7%). 3, 9
Tenecteplase showed reduced mortality in patients receiving treatment more than 4 hours after symptom onset (7% vs 9.2%, p=0.018) and lower rates of non-cerebral bleeding (26.4% vs 29.0%, p=0.0003). 9, 5
Critical Safety Considerations
Avoid tenecteplase in patients >75 years when using enoxaparin as ancillary therapy due to increased intracranial hemorrhage risk demonstrated in ASSENT-3 PLUS. 8
Avoid low molecular weight heparin in patients with significant renal dysfunction (serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women). 2
The risk of intracranial hemorrhage is 0.9-1.0% overall, increased with lower weight, female sex, previous cerebrovascular disease, and hypertension on admission. 4