Tenecteplase (TNKase) is a modified tissue plasminogen activator (tPA) designed to break down blood clots by converting plasminogen to plasmin, which then degrades fibrin. Its use is indicated in emergency medical situations requiring rapid intervention. The FDA has approved tenecteplase for two primary conditions.
FDA-Approved Indications for Tenecteplase
Acute ST-Elevation Myocardial Infarction (STEMI)
For over two decades, tenecteplase has been approved to reduce mortality in patients with acute ST-elevation myocardial infarction (STEMI), a severe heart attack caused by a completely blocked coronary artery. It is particularly useful when immediate primary percutaneous coronary intervention (PCI) is not feasible. The convenience of a single, weight-based intravenous bolus is a key benefit in emergency STEMI management.
Acute Ischemic Stroke (AIS)
In March 2025, tenecteplase received FDA approval for the treatment of acute ischemic stroke (AIS), which occurs due to a blood clot in the brain. It provides an alternative to alteplase, the previous standard of care. Tenecteplase for AIS must be administered within 3 hours of symptom onset. Studies, such as the AcT trial, demonstrated that tenecteplase was comparable to alteplase in preventing disability and safety. Its single-bolus administration is advantageous for timely stroke treatment.
Comparison of Tenecteplase and Alteplase
Tenecteplase is a bioengineered version of alteplase with distinct pharmacological properties.
| Feature | Tenecteplase (TNK) | Alteplase (r-tPA) |
|---|---|---|
| Mechanism | Higher fibrin specificity, increased resistance to PAI-1. | Lower fibrin specificity, less resistant to PAI-1. |
| Half-Life | Longer half-life (approx. 20-24 minutes). | Shorter half-life (approx. 5 minutes). |
| Administration | Single IV bolus over 5 seconds. | IV bolus followed by a 1-hour infusion. |
| Logistical Benefit | Simpler, faster, easier administration; reduces door-to-needle time. | More complex, requiring infusion pumps and longer administration time. |
| Efficacy in LVO Stroke | Some trials show higher rates of reperfusion and non-inferiority. | Long-standing standard of care, but may be surpassed by TNK in certain contexts. |
Off-Label Use for Pulmonary Embolism (PE)
Tenecteplase is not FDA-approved for pulmonary embolism (PE), but it may be used off-label in high-risk or massive PE cases, which involve significant hemodynamic instability due to a blood clot in the pulmonary artery. However, its use in intermediate-risk PE has been associated with an increased risk of major bleeding and hemorrhagic stroke, as seen in studies like the PEITHO trial. Therefore, using tenecteplase for PE requires careful assessment of risks versus benefits.
Warnings, Precautions, and Side Effects
As a thrombolytic, tenecteplase carries a substantial risk of bleeding, including potentially life-threatening intracranial hemorrhage. For details on potential side effects and contraindications, refer to {Link: The Medical Letter https://secure.medicalletter.org/TML-article-1727d}.
Conclusion
Tenecteplase is an important thrombolytic agent approved by the FDA for the treatment of acute ST-elevation myocardial infarction and acute ischemic stroke. For additional details on tenecteplase in acute ischemic stroke, refer to resources such as this review from the American Heart Association Journals {Link: American Heart Association Journals https://www.ahajournals.org/doi/10.1161/JAHA.123.031692}.
