Thrombolytic

Tenecteplase

Also called TNK

Reviewed by Alex G, BSN, RN, CEN, CCRN, CMC, NREMT-P · From the Reference tab of the app

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)

On the quick cards

Thrombolytics (-teplase)NCLEX Drug Classes: Acute ischemic stroke, MI, massive PE

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

Safety

Symptomatic ICH 3.4% vs 3.1% with alteplase in the label stroke trial (AcT, 0–3 h); ICH 0.9% in STEMI (ASSENT-2), more in older patients
Dose errors: the stroke dose (0.25 mg/kg, max 25 mg) is half the STEMI dose (max 50 mg); check the table and vial
STREAM halved the STEMI dose at 75 or older after excess intracranial bleeding (1.0% vs 0.2% with PCI)
Contraindicated with active bleeding, intracranial or spinal surgery or trauma within 2 months, bleeding diathesis or severe uncontrolled hypertension; for STEMI also prior ICH or stroke within 3 months (label)
Post-lysis care as for alteplase: BP below 180/105 and no antithrombotics for 24 h after stroke lysis
Orolingual angioedema in 1.0% vs 1.4% with alteplase in the same trial; anaphylaxis is rare (label)
No antidote: cryoprecipitate to fibrinogen 150 mg/dL or more plus tranexamic acid for symptomatic bleeding

In the algorithms

Stroke Code

Alteplase

Practice free in your browser2,150+ 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 the order, the label and your institution's protocols.