Tenecteplase Dosing for Acute 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
Weight-Based Dosing Regimen
The European Society of Cardiology establishes the following weight-tiered dosing schedule for tenecteplase administration 1:
- <60 kg: 30 mg (6 mL)
- 60 to <70 kg: 35 mg (7 mL)
- 70 to <80 kg: 40 mg (8 mL)
- 80 to <90 kg: 45 mg (9 mL)
- ≥90 kg: 50 mg (10 mL)
The drug is administered as a single intravenous bolus over 5-10 seconds, which represents a major practical advantage over alteplase's 90-minute infusion 3, 2, 4. This weight-adjusted dosing was developed because total body weight explains 19% of the variability in plasma clearance, with each 10 kg increase in body weight resulting in a 9.6 mL/min increase in clearance 5.
Timing and Clinical Context
Tenecteplase must be administered within 12 hours of symptom onset, with greatest benefit occurring with earlier administration 3. The drug is indicated when primary PCI cannot be performed by an experienced team within 120 minutes of first medical contact 3. For patients presenting very early (<2 hours) with large infarcts and low bleeding risk, fibrinolysis should be considered if time from first medical contact to balloon inflation exceeds 90 minutes 3.
Mandatory Adjunctive Therapy
Antiplatelet Agents
Aspirin is required with a loading dose of 150-300 mg orally or 80-150 mg IV if oral administration is not possible, followed by 75-100 mg daily maintenance 3. The European Society of Cardiology also specifies that aspirin can be given at 150-500 mg orally or 250 mg IV 1.
Clopidogrel must be administered with a loading dose of 300 mg orally if aged ≤75 years, followed by 75 mg daily maintenance 1, 3. For patients >75 years, no loading dose is given 3.
Anticoagulation (Required)
Anticoagulation is mandatory until revascularization or for the duration of hospital stay up to 8 days 3. The preferred options are:
Enoxaparin (preferred over unfractionated heparin) 3:
- Patients <75 years: 30 mg IV bolus, then 1 mg/kg subcutaneous every 12 hours (maximum 100 mg for first two doses) 1
- Patients ≥75 years: No IV bolus; start with 0.75 mg/kg subcutaneous every 12 hours (maximum 75 mg for first two doses) 1
- Renal impairment (creatinine clearance <30 mL/min): Subcutaneous doses given once every 24 hours regardless of age 1
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
- Target aPTT: 50-70 seconds or 1.5-2.0 times control, monitored at 3,6,12, and 24 hours 1
The combination of tenecteplase, aspirin, enoxaparin, and clopidogrel has been most extensively studied as part of pharmacoinvasive strategies 1.
Clinical Efficacy Evidence
The ASSENT-2 trial (16,949 patients) demonstrated that tenecteplase achieves equivalent 30-day mortality compared to alteplase (6.2% for both), with similar rates of intracranial hemorrhage (0.9% vs 0.9%) and stroke (1.8% vs 1.7%) 2, 6, 7. However, tenecteplase showed significantly fewer non-cerebral bleeding complications (26.4% vs 29.0%, p=0.0003) 6, 4. Exploratory analyses suggested reduced mortality in patients receiving treatment more than 4 hours after symptom onset (7% vs 9.2%, p=0.018) 6.
Post-Administration Management
All patients must be transferred to a PCI-capable center following fibrinolysis 3. Monitor ST-segment elevation, cardiac rhythm, and clinical symptoms over 60-180 minutes after initiation 3. 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 3.
Rescue PCI is indicated immediately if fibrinolysis fails (<50% ST-segment resolution at 60 minutes) 3. For stable patients after successful fibrinolysis, routine angiography with view to revascularization should occur at 3-24 hours 1.
Critical Safety Considerations and Pitfalls
Do not use tenecteplase in combination with planned primary PCI when PCI can be performed promptly. The ASSENT-4 PCI trial was terminated early due to higher mortality with tenecteplase plus PCI versus PCI alone (6.7% vs 4.9%), with increased rates of cardiogenic shock, CHF, recurrent MI, and repeat revascularization 2.
Avoid low molecular weight heparin in patients >75 years when using tenecteplase, and avoid LMWH in patients with significant renal dysfunction (serum creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) 3.
Do not use GP IIb/IIIa inhibitors within 12 hours before tenecteplase administration, and their use is discouraged for the first 24 hours following administration 2.
The pharmacokinetic profile of tenecteplase shows a biphasic disposition with initial half-life of 17-24 minutes and terminal half-life of 90-130 minutes, which is 6-fold longer than alteplase's 3.5 minutes 5. This prolonged half-life, combined with 15-fold higher fibrin specificity and 80-fold reduced PAI-1 binding, enables the single bolus administration 5.