Thrombolytic
Tenecteplase
Also called TNK
Indications
- Acute ischemic stroke within 3 h (label, 2025), or to 4.5 h as an equal choice to alteplase (AHA/ASA 2026; off-label beyond 3 h)
- Large vessel occlusion stroke before thrombectomy or transfer
- STEMI, to reduce mortality (label), when PCI within 120 min is not possible
- Massive pulmonary embolism or cardiac arrest from it (off-label)
Mechanism of action
Tenecteplase is an engineered variant of human tissue plasminogen activator that, like alteplase, binds fibrin and converts clot-bound plasminogen to plasmin. Three amino acid changes slow its liver clearance and make it about 14 times more fibrin-specific and 80 times more resistant to PAI-1 than alteplase (Keyt 1994), so a single bolus gives sustained lysis with less loss of circulating fibrinogen.
Pharmacology
- Hematologic: fibrinogen falls only 4–15% and plasminogen 11–24% after STEMI doses, against a 16–36% fibrinogen fall with alteplase (labels)
- CNS: matched alteplase for 90-day function in stroke; before thrombectomy it reperfused more (22% vs 10%; EXTEND-IA TNK 2018)
- Cardiovascular: in STEMI, 30-day mortality equaled accelerated alteplase (6.2%; ASSENT-2) with fewer non-cerebral bleeds (26.4% vs 29.0%)
- Respiratory: in intermediate-high-risk PE it prevented collapse but raised hemorrhagic stroke (2.0% vs 0.2%; PEITHO 2014)
Pharmacokinetics
| Onset | Minutes after a single IV bolus over 5 s |
|---|---|
| Duration | Bleeding risk outlasts plasma levels |
| Half-life | Initial 20–24 min (older label); terminal 90–130 min (label) |
| Distribution | Central Vd 4.2–5.4 L, about plasma volume; steady state 6.1–8.0 L (label) |
| Metabolism | Hepatic uptake and breakdown, slower than alteplase |
| Clearance | 99–119 mL/min, about a quarter of alteplase's (label) |
| Routes | IV bolus only; flush dextrose lines with saline before and after (it precipitates) |
Chemistry
- A 527-amino acid glycoprotein of 58,742 Da (label) from CHO cells; TNK names the three altered sites
- T103N adds a sugar chain to kringle 1 and N117Q removes the high-mannose chain liver receptors bind; both slow clearance
- Four alanines replace KHRR at positions 296–299 in the protease domain, giving PAI-1 resistance and fibrin specificity
- Lyophilized 25 mg (stroke) and 50 mg (STEMI) vials with L-arginine, phosphoric acid and polysorbate 20; 5 mg/mL in sterile water, pH about 7.3; do not shake; use within 8 h
Adverse effects and cautions
In the one-pagers
- Pulmonary EmbolismReperfusion and the PE response team: Systemic lysis is harmful in A to C2. PEITHO (tenecteplase, intermediate-high): death or collapse 2.6% vs 5.6%, hemorrhagic stroke 2.0% vs 0.2%. HI-PEITHO (2026): catheter lysis 4.0% vs 10.3%, no intracranial bleeds. PERT review: Class 1 for C to E.
- ACS and STEMIReperfusion: timelines and strategy: If PCI within 120 min is impossible and symptoms began under 12 h ago, lyse within 30 min and transfer: emergently for failed reperfusion or shock, otherwise for angiography at 2–24 h. In STREAM (2013), in patients seen within 3 h, this pharmacoinvasive approach matched primary PCI (30-day composite 12.4% vs 14.3%), but intracranial hemorrhage ran 1.0% vs 0.2%
- Neuro: ICP and StrokeAcute ischemic stroke: Tenecteplase: 0–4.5 h: 0.25 mg/kg IV push, max 25 mg
Practice Pulmonary Embolism questions free8 exam-style questions with rationales on the topic where Tenecteplase comes up most. No account or download needed.
In the algorithms
Other thrombolytic drugs
Practice free in your browser2,450+ exam-style questions with rationales. No account, no ads. Also free on the App Store and Google Play.
Sources
- FDA label: TNKase (2025)
- Keyt 1994 (PNAS)
- ASSENT-2 (Lancet 1999)
- AHA/ASA acute ischemic stroke guideline (2026)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.