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Inj tenectaplase

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Injection Tenecteplase (TNK-tPA)

Drug Class

Third-generation fibrinolytic (thrombolytic) agent — a genetically engineered variant of tissue plasminogen activator (tPA).

Mechanism of Action

Tenecteplase activates plasminogen to plasmin, which degrades fibrin clots. Three key genetic modifications distinguish it from alteplase:
ModificationEffect
New glycosylation site added to kringle-1 domainLonger half-life (20–24 min vs. ~5 min for alteplase)
Removal of existing glycosylation site on kringle-1Restores fibrin affinity
Tetra-alanine substitution at residues 296–29980× greater PAI-1 resistance than alteplase
  • 14× more fibrin-specific than alteplase → selective clot lysis, less systemic fibrinogenolysis
  • Does not stimulate thrombin-antithrombin complex formation (unlike streptokinase and alteplase), potentially reducing bleeding risk
  • Lower affinity for (DD)E fragment → less systemic plasminogen activation
— Tintinalli's Emergency Medicine, Braunwald's Heart Disease, Harrison's Principles of Internal Medicine 22E

Indications

  1. STEMI (ST-elevation myocardial infarction) — primary indication when PCI is not available within 120 minutes
  2. Acute Ischemic Stroke — used in many countries; AHA/ASA 2018 guidelines give a Class IIb recommendation as an alternative to alteplase

Dosing

STEMI

Weight-based single IV bolus (advantage: no infusion required):
Body WeightDose
< 60 kg30 mg
60–69 kg35 mg
70–79 kg40 mg
80–89 kg45 mg
≥ 90 kg50 mg (maximum)
  • Given as a single IV bolus over 5–10 seconds

Acute Ischemic Stroke

  • 0.25 mg/kg IV bolus over 5 seconds, maximum 25 mg
    • (Lower dose than for STEMI — higher doses associated with increased ICH risk)
— Swanson's Family Medicine Review, Harrison's 22E, Rosen's Emergency Medicine

Comparison with Alteplase (in STEMI)

  • Equal 30-day mortality (non-inferior in phase III trial of >16,000 patients)
  • Similar intracranial hemorrhage rates
  • Less non-cerebral bleeding and reduced need for blood transfusions
  • Simpler administration (single bolus vs. weight-adjusted infusion) → fewer medication errors

Contraindications

Absolute:
  • Any prior intracranial hemorrhage
  • Known intracranial structural lesion (AVM, tumor)
  • Ischemic stroke within 3 months (except acute stroke within 4.5 h)
  • Suspected aortic dissection
  • Active bleeding / bleeding diathesis
  • Significant head/facial trauma within 3 months

Key Advantages Over Alteplase

  • Single-bolus administration (no infusion) → improves workflow, simplifies transfer to cath lab / thrombectomy centre
  • Higher fibrin specificity → less systemic plasmin generation
  • PAI-1 resistant → prolonged clot-bound activity
  • Fewer non-cerebral bleeding complications

Important Notes

  • Administer with concomitant anticoagulation (unfractionated heparin or enoxaparin) per STEMI protocol
  • In stroke, tenecteplase obviates need for a 1-hour infusion, simplifying transfer for mechanical thrombectomy
  • Not associated with allergic reactions (unlike streptokinase)
— Braunwald's Heart Disease, Tintinalli's Emergency Medicine, Harrison's Principles of Internal Medicine 22E, Rosen's Emergency Medicine
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