What is the appropriate dosing, administration protocol, contraindications, and monitoring for tenecteplase (TNK) in a patient with acute ST‑segment‑elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention cannot be performed within the recommended time window?

Tenecteplase for STEMI When Primary PCI Cannot Be Performed Within 120 Minutes

Administer tenecteplase as a single weight-based IV bolus when primary PCI cannot be performed within 120 minutes of first medical contact in patients with STEMI presenting within 12 hours of symptom onset and no contraindications. 1

Indications and Timing

• Initiate tenecteplase when anticipated time from first medical contact to primary PCI exceeds 120 minutes in patients with ischemic symptoms less than 12 hours duration 1
• Consider fibrinolysis for patients presenting 12-24 hours after symptom onset if there is ongoing ischemia, large area of myocardium at risk, or hemodynamic instability 1
• Greatest mortality benefit occurs with earlier administration, particularly within the first 2 hours of symptom onset 1, 2
• For very early presenters (<2 hours) with large infarct and low bleeding risk, consider fibrinolysis if time to balloon inflation exceeds 90 minutes 2

Weight-Based Dosing Protocol

Administer as a single IV bolus over 5 seconds using the following weight-adjusted doses 1, 3:

• <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)

Critical Dosing Modification

• For patients ≥75 years old, reduce dose by 50% to decrease stroke risk 4
• Avoid enoxaparin as adjunctive therapy in patients >75 years due to increased intracranial hemorrhage risk 2, 5

Reconstitution and Administration

• Reconstitute 50 mg vial with 10 mL Sterile Water for Injection (supplied) to achieve 5 mg/mL concentration 3
• Gently swirl until dissolved; DO NOT SHAKE 3
• Allow large bubbles to dissipate by standing undisturbed for several minutes 3
• Flush dextrose-containing IV lines with 0.9% sodium chloride before and after administration to prevent precipitation 3
• Use large-bore peripheral IV (18-20 gauge) or central venous access 6
• Administer as single bolus over 5 seconds 3
• If not used immediately, refrigerate at 2-8°C and use within 8 hours 3

Absolute Contraindications

Do not administer tenecteplase if any of the following are present 1, 3:

• Any prior intracranial hemorrhage
• Known structural cerebral vascular lesion (arteriovenous malformation, aneurysm)
• 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 mmHg or DBP >110 mmHg unresponsive to therapy)

Relative Contraindications

Exercise caution and weigh risks versus benefits 1:

• History of chronic, severe, poorly controlled hypertension
• History of ischemic stroke >3 months ago
• Dementia
• Traumatic or prolonged CPR (>10 minutes)
• Major surgery within 3 weeks
• Recent internal bleeding (within 2-4 weeks)
• Noncompressible vascular punctures
• Pregnancy or within 1 week postpartum
• Active peptic ulcer
• Oral anticoagulant therapy
• Advanced liver disease
• Infective endocarditis

Important Clarification

• Successful resuscitation does NOT contraindicate fibrinolytic therapy 1
• Do NOT administer for ST depression unless true posterior MI suspected or ST elevation in lead aVR present 1

Mandatory Adjunctive Antiplatelet Therapy

Aspirin

• Administer 150-300 mg oral loading dose (chewed) or 80-150 mg IV if oral not possible 1, 2
• Continue 75-100 mg daily thereafter 1

P2Y12 Inhibitor

• Administer clopidogrel loading dose in addition to aspirin 1, 2, 4
• For patients ≤75 years: 300 mg loading dose 1

Mandatory Adjunctive Anticoagulation

Continue anticoagulation until revascularization or for duration of hospital stay (up to 8 days) 2, 4:

Preferred Option: Enoxaparin

• 30 mg IV bolus followed by 1 mg/kg subcutaneous every 12 hours 2, 5
• Maximum 7 days duration 5
• Avoid in patients >75 years (use UFH instead) 2, 5
• Avoid if serum creatinine >2.5 mg/dL (men) or >2.0 mg/dL (women) 2

Alternative: Unfractionated Heparin

• 60 units/kg IV bolus (maximum 4000 units) 1
• 12 units/kg/hour infusion (maximum 1000 units/hour) 1
• Target aPTT 50-75 seconds 1
• Continue for 48 hours 5

Post-Administration Monitoring Protocol

Immediate Assessment (60-90 minutes)

Monitor for signs of successful reperfusion 2:

• ≥50% reduction in ST-segment elevation on repeat ECG at 60-90 minutes
• Relief of chest pain symptoms
• Maintenance or restoration of hemodynamic stability
• Absence of ventricular arrhythmias

Failed Reperfusion Indicators

Proceed immediately to rescue PCI if 2, 4:

• <50% ST-segment resolution at 60-90 minutes
• Persistent chest pain
• Hemodynamic instability (systolic BP <100 mmHg, heart rate >100 bpm)
• Electrical instability (ventricular arrhythmias)
• Cardiogenic shock (Killip class II-III)

Mandatory Transfer and PCI Strategy

All Patients

• Transfer to PCI-capable center immediately after tenecteplase administration without waiting to assess reperfusion success 2, 4
• Do not delay transfer to determine whether fibrinolysis was successful 4

Successful Fibrinolysis

• Perform coronary angiography and PCI of infarct-related artery between 2-24 hours after tenecteplase 2, 4
• This pharmacoinvasive strategy reduces mortality by 38% and reinfarction by 41% compared to delayed or ischemia-driven PCI 4

Failed Fibrinolysis

• Perform rescue PCI immediately (within 60-90 minutes of tenecteplase) 2, 4

Bleeding Complications Management

If Serious Bleeding Occurs

• Discontinue concomitant heparin and antiplatelet agents immediately 3
• Apply local pressure if accessible bleeding site 3
• Administer blood products as needed 3

Expected Bleeding Rates

• Intracranial hemorrhage: 0.93% (similar to alteplase) 7
• Non-cerebral bleeding: 26.4% (lower than alteplase at 29%) 7
• Blood transfusion requirement: 4.3% (lower than alteplase at 5.5%) 7

Critical Pitfalls to Avoid

Do NOT Use Facilitated PCI Strategy

• Do not administer full-dose tenecteplase immediately before planned primary PCI (within 1-3 hours) 8
• This strategy increases in-hospital mortality (6% vs 3%), stroke (1.8% vs 0%), and reinfarction (6% vs 4%) 8
• The evidence from ASSENT-4 PCI trial definitively shows harm with this approach 8

Do NOT Re-administer Streptokinase

• Tenecteplase can be safely re-administered as it does not cause antibody formation 6
• However, never re-administer streptokinase due to antibody formation and allergic reaction risk 1

Avoid Dextrose Solutions

• Tenecteplase precipitates in dextrose-containing solutions 3
• Always flush lines with 0.9% sodium chloride 3

Age-Related Considerations

• Reduce dose by 50% in patients ≥75 years 4
• Use UFH instead of enoxaparin in patients >75 years to avoid excess intracranial hemorrhage 2, 5

Pharmacologic Advantages

• Terminal half-life of 17-24 minutes (initial phase) allows single-bolus administration 9
• 80-fold reduced binding to PAI-1 compared to alteplase provides superior resistance to inhibition 9, 10
• 15-fold higher fibrin specificity than alteplase reduces systemic fibrinolysis 9, 10
• Equivalent 30-day mortality to alteplase (6.18% vs 6.15%) with easier administration 7