TNKase (Tenecteplase)
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Acute ischemic stroke (AIS) | Adults; initiate as soon as possible and within 3 hours of symptom onset (per FDA label); active intracranial haemorrhage excluded by imaging | Monotherapy with concomitant supportive care | FDA Approved (2/2025) |
| Acute ST-elevation myocardial infarction (STEMI) | Adults — to reduce the risk of death associated with acute STEMI | With concomitant aspirin and IV heparin (per ASSENT-2 evidence) | FDA Approved (2000) |
Tenecteplase is a genetically modified recombinant human tissue plasminogen activator developed to retain the fibrin-binding properties of native t-PA while increasing fibrin specificity, prolonging plasma half-life, and reducing inhibition by plasminogen activator inhibitor-1. These pharmacological modifications enable single-bolus dosing rather than the prolonged infusion required for alteplase. Initial U.S. approval for STEMI was 2000. The acute ischemic stroke indication was added in February 2025 on the basis of the AcT non-inferiority trial (Menon BK et al, Lancet 2022). TNKase is currently the only single-bolus thrombolytic FDA-approved for both acute STEMI and AIS in the United States.
AIS within the 3 to 4.5-hour window — the FDA AIS label restricts the approved indication to within 3 hours of symptom onset. Per the FDA prescribing information, the AcT trial enrolled patients up to 4.5 hours, but only the 0–3 hour subset (n = 1147) was used to assess efficacy because the comparator (alteplase) is approved only for that window. The ATTEST-2 trial (UK, 2024; n = 1858) confirmed non-inferiority between 0 and 4.5 hours, and AHA/ASA stroke guidelines support tenecteplase as an alternative to alteplase in selected patients within 4.5 hours of symptom onset; verify the current AHA/ASA guideline recommendation in force at the time of practice. Evidence quality: high (multiple non-inferiority RCTs).
AIS in patients eligible for endovascular thrombectomy — single-bolus tenecteplase as the bridging thrombolytic before mechanical thrombectomy is widely used and was tested in EXTEND-IA TNK; logistical advantages over alteplase include faster administration and simpler interhospital transfer. Off-label per the strict 0–3 hour FDA AIS window but supported by published RCT evidence and registry data. Evidence quality: moderate to high.
AIS in the 4.5 to 9-hour window with imaging selection — investigational/off-label use guided by perfusion-imaging selection (CT perfusion or MRI mismatch). Recent AHA/ASA updates have introduced extended-window thrombolysis recommendations; confirm the current guideline at the time of practice. Evidence quality: moderate.
Massive / submassive pulmonary embolism — tenecteplase has been tested in PE (e.g., the PEITHO trial in intermediate-risk PE) but is not FDA-approved for this indication. PEITHO showed reduced haemodynamic decompensation but increased major bleeding without overall mortality benefit. Evidence quality: moderate (single RCT; not approved).
Dosing
Tenecteplase is administered as a single intravenous bolus over 5 seconds. Dose is weight-tiered and indication-specific, with different maximum doses for AIS (25 mg) and STEMI (50 mg). The AIS regimen targets approximately 0.25 mg/kg, and the STEMI regimen targets approximately 0.5–0.6 mg/kg (about twice the AIS dose). Both vial strengths reconstitute to a final concentration of 5 mg/mL. Tenecteplase is incompatible with dextrose-containing solutions; flush dextrose lines with 0.9% sodium chloride before and after the bolus. Reconstitute immediately before use; if not used immediately, the reconstituted solution may be refrigerated at 2–8 °C and used within 8 hours.
Acute Ischemic Stroke — Maximum Dose 25 mg
| Patient Weight | TNKase Dose | Volume to Administer | Notes |
|---|---|---|---|
| < 60 kg | 15 mg | 3 mL | Confirm no intracranial haemorrhage on imaging before bolus Pretreatment BP must be < 185/110 mm Hg (per AHA/ASA standards) |
| 60 to < 70 kg | 17.5 mg | 3.5 mL | No antiplatelet or other antithrombotic agents within 24 h after bolus (per AcT trial protocol and FDA PI) |
| 70 to < 80 kg | 20 mg | 4 mL | Initiate as soon as possible and within 3 hours of symptom onset |
| 80 to < 90 kg | 22.5 mg | 4.5 mL | If pretreatment INR > 1.7 or aPTT elevated in patients without recent anticoagulant use, monitor closely (per FDA PI Section 2.1) |
| ≥ 90 kg | 25 mg | 5 mL | Maximum recommended AIS dose; do not exceed |
Acute STEMI — Maximum Dose 50 mg
| Patient Weight | TNKase Dose | Volume to Administer | Notes |
|---|---|---|---|
| < 60 kg | 30 mg | 6 mL | Initiate as soon as possible after onset of STEMI symptoms Concomitant aspirin 150–325 mg loading and IV heparin per ASSENT-2 protocol |
| 60 to < 70 kg | 35 mg | 7 mL | For weight ≤ 67 kg in ASSENT-2: heparin 4000-unit IV bolus then 800 U/h infusion |
| 70 to < 80 kg | 40 mg | 8 mL | For weight > 67 kg in ASSENT-2: heparin 5000-unit IV bolus then 1000 U/h infusion; aPTT target 50–75 s |
| 80 to < 90 kg | 45 mg | 9 mL | Patients should not have received GP IIb/IIIa inhibitors in the prior 12 h (per ASSENT-2 exclusion) |
| ≥ 90 kg | 50 mg | 10 mL | Maximum recommended STEMI dose; do not exceed Choose either thrombolysis or primary PCI as the reperfusion strategy — do not routinely combine |
Population-Specific Considerations
| Population | Adjustment | Rationale |
|---|---|---|
| Geriatric (≥ 65 years), AIS | No formal dose adjustment | 72% of AcT TNKase patients (426/592) were ≥ 65 yr; 49% (290/592) were ≥ 75 yr; no overall safety differences observed (FDA PI Section 8.5), but greater sensitivity in some older individuals cannot be excluded |
| Geriatric (≥ 65 years), STEMI | No formal dose adjustment; counsel on increased risk | In ASSENT-2, 41% (3500/8458) of TNKase-treated STEMI patients were ≥ 65 yr; this group had higher rates of 30-day mortality, stroke, ICH, and major bleeds than younger patients (per FDA PI Section 8.5) |
| Renal impairment | No specified adjustment | Clearance is hepatic; severe renal disease may increase bleeding risk via uraemic platelet dysfunction (FDA PI Section 5.1) |
| Hepatic impairment | Use with caution | Significant hepatic dysfunction is listed by the FDA PI Section 5.1 as a condition that increases bleeding risk; weigh against anticipated benefit |
| Pediatric AIS / STEMI | Not established | Per FDA PI Section 8.4, safety and effectiveness in paediatric patients have not been established |
Tenecteplase’s single 5-second bolus is its principal practical advantage. Both vial strengths are supplied as lyophilised powder under partial vacuum, co-packaged with the appropriate volume of Sterile Water for Injection (5.2 mL for the 25 mg vial, 10 mL for the 50 mg vial). Reconstitute only with the supplied diluent (no preservative); both vials yield a final concentration of 5 mg/mL. Slight foaming is normal — let the bubbles settle, then swirl gently (do not shake). Withdraw the weight-based volume into a syringe and connect directly to the IV port. Flush dextrose-containing IV lines with 0.9% sodium chloride before and after the bolus — tenecteplase precipitates in dextrose. Discard any unused reconstituted solution after 8 hours of refrigerated storage.
Three Genentech thrombolytics are commonly confused: TNKase (tenecteplase, single 5-second IV bolus, weight-tiered to 25 mg max for stroke or 50 mg max for STEMI), Activase (alteplase 50 / 100 mg vials, IV bolus + 60-minute infusion for stroke or weight-banded 90-minute infusion for STEMI), and Cathflo Activase (alteplase 2 mg vial, intracatheter only). The FDA has issued specific medication-error alerts about confusion between these products. Verify the product name, vial strength, indication, and weight band on every order.
Pharmacology
Mechanism of Action
Tenecteplase is a 527-amino-acid glycoprotein produced by recombinant DNA technology in a Chinese hamster ovary cell line (per FDA PI Section 11). It was bioengineered from native human tissue plasminogen activator by introducing three deliberate substitutions: threonine 103 to asparagine and asparagine 117 to glutamine in the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain. Its molecular weight is 58,742 daltons and biological potency is expressed as 200 tenecteplase specific units per milligram. These modifications increase the molecule’s resistance to plasminogen activator inhibitor-1, prolong its plasma half-life, and increase fibrin specificity. Like alteplase, tenecteplase binds to fibrin within a thrombus and converts entrapped plasminogen to plasmin, which then degrades the fibrin matrix and lyses the clot. In vitro studies show enhanced relative conversion of plasminogen to plasmin in the presence of fibrin compared with alteplase. The FDA prescribing information explicitly notes that the clinical significance of this fibrin specificity for safety (e.g., bleeding) or efficacy has not been established.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | IV administration only — single 5-second bolus reconstituted to 5 mg/mL | No oral bioavailability (large glycoprotein); precipitates in dextrose-containing solutions — flush lines with normal saline |
| Distribution | Biphasic disposition; central Vd 4.2–5.4 L (≈ plasma volume); steady-state Vd 6.1–8.0 L (~50% greater, suggesting some extravascular distribution) | Local fibrin-bound action at the thrombus; modest extravascular distribution |
| Metabolism | Hepatic clearance is the major elimination mechanism; degraded as a protein | Significant hepatic dysfunction increases bleeding risk and warrants caution |
| Elimination | Terminal phase half-life 90–130 min in STEMI patients; plasma clearance 99–119 mL/min for 30–50 mg doses (linear PK); body weight explains 19% of clearance variability and 11% of Vd variability | Longer terminal half-life than alteplase enables single-bolus dosing rather than continuous infusion |
At STEMI doses (30–50 mg bolus), tenecteplase produces only a 4–15% reduction in circulating fibrinogen and an 11–24% reduction in plasminogen (per FDA PI Section 12.2). For comparison, alteplase at a 100 mg dose reduces fibrinogen by 16–36%. The lesser systemic fibrinogen depletion is a direct consequence of tenecteplase’s enhanced fibrin specificity. Whether this translates into a clinically meaningful difference in bleeding risk is not established by either label, although large randomised trials (ASSENT-2, AcT, ATTEST-2) have shown comparable safety profiles overall.
Immunogenicity
In a study of patients with STEMI, four of 625 (0.64%) patients tested for anti-drug antibodies had a positive antibody titre at 30 days (FDA PI Section 12.6). The clinical relevance of this low-frequency finding is unclear; tenecteplase is administered as a single dose, so chronic immunogenicity is not a practical concern.
Side Effects
The FDA prescribing information identifies bleeding as the most frequent adverse reaction across both approved indications. Adverse-reaction rates are drawn directly from FDA PI Table 3 (AcT trial, AIS) and Table 5 (ASSENT-2 trial, STEMI). Because tenecteplase has been tested head-to-head against alteplase in both indications, the figures below include the comparator rates from those trials.
| Adverse Effect | Incidence (TNKase) | Clinical Note |
|---|---|---|
| Death (90-day) — AIS cohort | 15.0% | Identical to alteplase comparator (15.0%) per FDA PI Table 3; reflects underlying stroke severity rather than drug toxicity |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Death or non-fatal stroke at 30 days (STEMI — ASSENT-2) | 7.1% | Alteplase 7.0%; relative risk 1.01 (95% CI 0.91–1.13); composite endpoint per FDA PI Table 5 |
| 30-day mortality (STEMI — ASSENT-2) | 6.2% | Identical to alteplase 6.2%; relative risk 1.00 (95% CI 0.89–1.12) per FDA PI Table 5 |
| Symptomatic intracerebral haemorrhage (AIS — AcT) | 3.4% | Alteplase 3.1% in the same trial; defined per FDA PI as ICH temporally related to and directly responsible for neurological worsening |
| Any stroke at 30 days (STEMI — ASSENT-2) | 1.8% | Alteplase 1.7%; relative risk 1.07 (95% CI 0.86–1.35) |
| Orolingual angioedema (AIS — AcT) | 1.0% | Alteplase 1.4% in the same trial; higher risk reported with concomitant ACE inhibitors |
| Extracranial bleeding requiring blood transfusion (AIS — AcT) | 1.0% | Alteplase 0.7%; per FDA PI Table 3 |
| Intracranial haemorrhage at 30 days (STEMI — ASSENT-2) | 0.9% | Alteplase 0.9%; relative risk 0.99 (95% CI 0.73–1.35) |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Symptomatic intracerebral haemorrhage (AIS) | 3.4% in AcT | Usually first 24–36 h | Urgent CT; cryoprecipitate ± antifibrinolytic (tranexamic acid or aminocaproic acid); platelet transfusion if low or on antiplatelet; neurosurgery consult |
| Major systemic bleeding | Increased over baseline; varies by site | During or after bolus; can occur 1+ days later if anticoagulated | Discontinue any concomitant heparin or antiplatelet immediately; pressure on compressible sites; cryoprecipitate; transfusion as needed |
| Hypersensitivity reactions (urticarial / anaphylactic) | Reported (frequency not quantified in PI) | During and for several hours after bolus | Antihistamines, corticosteroids, epinephrine; manage airway; includes anaphylaxis, angioedema, laryngeal oedema, rash, and urticaria |
| Cholesterol embolisation | Reported (incidence unknown) | Days after exposure | Recognise (livedo reticularis, purple toes, AKI, gangrenous digits, pancreatitis); supportive care; can be fatal |
| Reperfusion arrhythmias (STEMI) | Common during STEMI thrombolysis | Minutes to hours after bolus | Sinus bradycardia, AIVR, PVCs, VT — manage with standard antiarrhythmic measures; have antiarrhythmic therapy available at the bedside (per FDA PI Section 5.5) |
| Thromboembolism (left heart thrombus lysis) | Reported | During or after bolus | Higher risk in mitral stenosis or atrial fibrillation; consider risk-benefit before administration |
| Heart failure / recurrent ischaemia (STEMI + planned PCI) | Worse vs PCI alone (ASSENT-4 PCI) | Within 90 days of strategy | Do not routinely combine TNKase with planned primary PCI; choose one reperfusion strategy (per FDA PI Section 5.6) |
| Reason to Withhold or Reverse | Incidence | Context |
|---|---|---|
| Suspected intracranial haemorrhage | Per protocol | Acute neurological deterioration after bolus → urgent CT, stop concomitant anticoagulation, reverse with cryoprecipitate ± antifibrinolytic |
| Major extracranial bleeding | Per protocol | Stop all concomitant anticoagulants/antiplatelets; supportive transfusion; mechanical compression for accessible sites |
| Hypersensitivity / angioedema | Per protocol | Secure airway; antihistamines, corticosteroids, epinephrine |
| Pretreatment INR > 1.7 or aPTT elevated (AIS) | Per protocol | If labs return after bolus in patients without recent anticoagulant use, monitor closely (per FDA PI Section 2.1) |
Sudden neurological deterioration, severe headache, acute hypertension, nausea or vomiting after a tenecteplase bolus mandates urgent non-contrast CT. Discontinue any concomitant heparin or antiplatelet immediately. While imaging is pending, send fibrinogen, platelets, PT/aPTT, and type and crossmatch. If ICH is confirmed, administer cryoprecipitate (typically 10 units; target fibrinogen ≥ 150 mg/dL), consider an antifibrinolytic (tranexamic acid 1 g IV or aminocaproic acid), correct platelets if needed, and consult neurosurgery and haematology promptly. Reversal protocols vary by institution — follow local guidance. Note that the longer terminal half-life of tenecteplase (90–130 min) compared with alteplase means circulating drug may still be present at the time of recognition.
Drug Interactions
The FDA prescribing information for TNKase has a brief Drug Interactions section (Section 7.1) that addresses primarily an in vitro coagulation-test artifact rather than direct drug–drug interactions. Clinically relevant interactions, however, are well established through the Warnings and Precautions section and through general antithrombotic pharmacology, and are summarised below.
The FDA prescribing information cautions that coagulation tests and measures of fibrinolytic activity may be unreliable during tenecteplase therapy because circulating drug remains active in vitro and can degrade fibrinogen in blood samples after collection (Section 7.1). Specific precautions (rapid sample handling and inhibitor addition) are required for accurate post-treatment fibrinogen measurement.
Monitoring
Tenecteplase requires intensive bedside monitoring after the bolus. The dominant priorities are early detection of bleeding (especially intracranial), tight blood-pressure control, airway assessment for hypersensitivity, and — for STEMI — surveillance for reperfusion arrhythmias. AHA/ASA stroke guidelines specify a structured neurological- and BP-monitoring schedule for the first 24 hours after AIS thrombolysis, summarised below.
-
Blood Pressure (AIS)
Every 15 min × 2 h, then q 30 min × 6 h, then q 60 min × 16 h
Routine Goal < 180/105 mm Hg for the first 24 h after AIS thrombolysis (AHA/ASA standards). Treat with IV labetalol, nicardipine, or clevidipine per institutional protocol. Pretreatment BP must be < 185/110 mm Hg before the bolus. -
Neurological Exam
Same schedule as BP for first 24 h
Routine NIHSS or focused neurological check; any acute deterioration mandates urgent CT to exclude ICH and immediate cessation of any concomitant anticoagulant. -
Bleeding Surveillance
Continuous after bolus; clinical monitoring ≥ 24 h
Routine Inspect arterial puncture sites, mucous membranes, urine, and stool. Avoid IM injections, urinary catheters, NG tubes, and central venous access during the first 24 h unless essential. The FDA PI specifically advises against internal jugular and subclavian venous punctures because these sites are not amenable to manual compression. -
Airway / Hypersensitivity
During and for several hours after bolus
Routine Inspect tongue and oropharynx; observe for urticaria, rash, and hypotension. Have antihistamines, corticosteroids, and epinephrine available. Higher angioedema risk in patients on ACE inhibitors. -
Cardiac Rhythm (STEMI)
Continuous telemetry
Routine Watch for reperfusion arrhythmias (sinus bradycardia, AIVR, PVCs, VT) and mechanical complications. Have antiarrhythmic therapy available at the bedside per FDA PI Section 5.5. -
Repeat CT (AIS)
At 24 h or sooner if deterioration
Routine Required before initiating antiplatelet or anticoagulant therapy after AIS thrombolysis; sooner if any neurological worsening, severe headache, or BP surge. -
Coagulation Panel
Baseline; repeat with bleeding
Trigger-based Pretreatment INR, aPTT, platelets, type and screen. In AIS without recent anticoagulant use, treatment can begin before results return; closely monitor if INR > 1.7 or aPTT elevated. -
Fibrinogen
If clinical bleeding
Trigger-based In the event of significant bleeding, send fibrinogen and target ≥ 150 mg/dL with cryoprecipitate; remember that in vitro degradation in untreated samples can artifactually lower the measured value. -
Glucose (AIS)
At presentation
Trigger-based Hypoglycaemia and severe hyperglycaemia can mimic stroke; the AHA/ASA guideline recommends correcting glucose abnormalities before treatment but does not categorically exclude eligible patients once glucose is corrected.
Contraindications & Cautions
Absolute Contraindications — Both AIS and STEMI (FDA PI Section 4)
- Active internal bleeding
- Intracranial or intraspinal surgery or trauma within 2 months
- Known bleeding diathesis
- Current severe uncontrolled hypertension — generally interpreted clinically as BP that cannot be lowered to < 185/110 mm Hg with antihypertensives prior to thrombolysis
- Presence of intracranial conditions that may increase the risk of bleeding — e.g., intracranial neoplasm, arteriovenous malformation, or aneurysm
Additional Contraindication — AIS Only
- Active intracranial haemorrhage — confirm absence by non-contrast CT before bolus
Additional Contraindications — STEMI Only
- History of intracranial haemorrhage (any prior — not just recent)
- History of ischaemic stroke within 3 months
Relative Contraindications (Specialist Input Recommended) — FDA PI Section 5.1
The FDA PI Section 5.1 lists conditions in which the bleeding risks of TNKase therapy for the approved indications are increased and should be weighed against the anticipated benefits:
- Recent major surgery or procedure — coronary artery bypass graft, obstetric delivery, organ biopsy, previous puncture of non-compressible vessels
- Cerebrovascular disease
- Recent intracranial haemorrhage (where not already an absolute contraindication)
- Recent gastrointestinal or genitourinary bleeding
- Recent trauma
- Hypertension — systolic BP above 175 mm Hg or diastolic BP above 110 mm Hg
- Acute pericarditis
- Subacute bacterial endocarditis
- Hemostatic defects, including those secondary to severe hepatic or renal disease
- Significant hepatic dysfunction
- Pregnancy
- Diabetic haemorrhagic retinopathy or other haemorrhagic ophthalmic conditions
- Septic thrombophlebitis or occluded AV cannula at a seriously infected site
- Advanced age — increased bleeding and ICH risk in older patients (especially in STEMI per ASSENT-2 sub-analyses)
- Patients currently receiving anticoagulants (e.g., warfarin)
- Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location
Use with Caution
- Concomitant ACE inhibitor — higher reported risk of orolingual angioedema (class effect for tPA agents); monitor airway during and after bolus.
- High likelihood of left heart thrombus — mitral stenosis, atrial fibrillation; risk of systemic embolisation as the lytic state acts on the thrombus (FDA PI Section 5.3).
- Planned primary PCI for STEMI — do not routinely combine TNKase with planned PCI; ASSENT-4 PCI showed worse outcomes versus PCI alone (FDA PI Section 5.6). Choose one reperfusion strategy.
- Pediatric use — safety and effectiveness not established (FDA PI Section 8.4).
- Pregnancy — animal data showed no maternal or developmental toxicity at ~7× human STEMI exposure; limited human data in case reports of related thrombolytics. The FDA PI explicitly states that life-sustaining therapy in pregnancy should not be withheld for STEMI or AIS because of potential fetal effects.
- Lactation — no human or animal milk data; risk-benefit decision based on the acuity of indication.
TNKase can cause significant, sometimes fatal, internal or external bleeding, especially at arterial and venous puncture sites. Concomitant drugs that impair haemostasis increase the risk further. Avoid intramuscular injections; minimise venipunctures; if arterial puncture is required during therapy, use an upper-extremity vessel accessible to manual compression and apply pressure for at least 30 minutes. There is no FDA boxed warning, but the bleeding caution is the central theme of the prescribing information.
Hypersensitivity reactions (urticarial / anaphylactic — including anaphylaxis, angioedema, laryngeal oedema, rash, urticaria) have been reported. Monitor patients during and for several hours after the bolus and treat with antihistamines, corticosteroids, and epinephrine if symptoms occur.
Coronary thrombolysis may produce reperfusion arrhythmias; have antiarrhythmic therapy available. Do not routinely combine TNKase with planned primary PCI for STEMI — ASSENT-4 PCI showed worse outcomes (mortality, cardiogenic shock, congestive heart failure, recurrent MI, and repeat revascularisation) versus PCI alone. Cholesterol embolisation has been rarely reported with thrombolytic agents.
Patient Counselling
Purpose of Therapy
Tenecteplase is an emergency, single-bolus therapy. Most patients (or surrogate decision-makers) receive it under acute, time-pressured conditions for either acute ischaemic stroke or ST-elevation myocardial infarction. Counselling typically occurs in two phases: a brief consent conversation before the bolus (when feasible) covering the trade-off between potential benefit and bleeding risk, and a more thorough post-treatment conversation about ongoing observation, recovery, and follow-up.
Before the Bolus (where time permits)
Explain in plain language that the medicine works by dissolving the clot blocking a brain artery (in stroke) or a heart artery (in STEMI). Earlier treatment increases the chance of a good outcome. The most important risk is bleeding — including bleeding into the brain, which in the AcT stroke trial occurred symptomatically in around 3 of every 100 patients treated and is sometimes fatal. Despite this risk, the trial evidence shows that tenecteplase is at least as effective as alteplase, with the practical advantage of a single 5-second injection rather than a 60-minute infusion. Allergic reactions, including swelling of the tongue and lips, are uncommon but possible, especially in patients on certain blood-pressure medicines.
Sources
- TNKase® (tenecteplase) US Prescribing Information. Genentech, Inc. Revised February 2025 (Reference ID: 5540622). accessdata.fda.gov Primary FDA label; source for indications, weight-based dosing tables, contraindications, adverse-reaction Tables 3 and 5, and pharmacokinetic values cited throughout this monograph.
- FDA Approves Genentech’s TNKase® in Acute Ischemic Stroke in Adults. Genentech press release, March 3, 2025. gene.com Documents the February 2025 FDA approval of TNKase for acute ischemic stroke and the introduction of the new 25 mg vial configuration.
- Menon BK, Buck BH, Singh N, et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022;400(10347):161-169. doi.org/10.1016/S0140-6736(22)01054-6 Pivotal AcT non-inferiority trial that supported FDA approval of tenecteplase for AIS; source of the 0–3 hour subgroup analysis (n = 1147) summarised in FDA PI Tables 3 and 4.
- Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet. 1999;354(9180):716-722. doi.org/10.1016/S0140-6736(99)07403-6 Pivotal STEMI non-inferiority trial (n = 16,949) demonstrating equivalence of single-bolus tenecteplase to accelerated alteplase for 30-day mortality; basis for FDA PI Table 5.
- Cannon CP, McCabe CH, Gibson CM, et al; TIMI 10A Investigators. TNK-tissue plasminogen activator in acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial. Circulation. 1997;95(2):351-356. doi.org/10.1161/01.cir.95.2.351 Phase 1 dose-ranging pharmacokinetic / pharmacodynamic study of tenecteplase in STEMI patients that established the basis for subsequent dose-finding.
- Muir KW, Ford GA, Ford I, et al; ATTEST-2 Investigators. Tenecteplase versus alteplase for acute stroke within 4·5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial. Lancet Neurology. 2024;23(11):1087-1096. doi.org/10.1016/S1474-4422(24)00377-6 UK non-inferiority trial (n = 1858) extending the AcT findings up to 4.5 hours after stroke onset; supports off-label use in the extended window.
- Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT-4 PCI) Investigators. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet. 2006;367(9510):569-578. doi.org/10.1016/S0140-6736(06)68147-6 Trial that demonstrated harm with routine combination of full-dose tenecteplase plus planned PCI versus PCI alone, underpinning FDA PI Section 5.6.
- Powers WJ, Rabinstein AA, Ackerson T, et al; American Heart Association Stroke Council. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke. Stroke. 2019;50(12):e344-e418. doi.org/10.1161/STR.0000000000000211 2019 AHA/ASA AIS guideline update — basis for the BP and post-thrombolysis monitoring targets cited in this monograph.
- American Heart Association / American Stroke Association. Most recent guideline for the early management of patients with acute ischemic stroke (published 2025/2026). Stroke. ahajournals.org/journal/str Most recent AHA/ASA AIS guideline addressing tenecteplase 0.25 mg/kg as an alternative to alteplase 0.9 mg/kg in selected patients within 4.5 hours, and the extended-window thrombolysis recommendation. Confirm the published citation (authors, journal, year, DOI) at the time of publication.
- O’Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation / American Heart Association Task Force. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. J Am Coll Cardiol. 2013;61(4):e78-e140. doi.org/10.1016/j.jacc.2012.11.019 ACC/AHA STEMI guideline — context for fibrinolytic therapy when timely PCI is not available, including weight-based tenecteplase dosing.
- TNKase® (tenecteplase) US Prescribing Information, Section 12.3 (Pharmacokinetics) and Section 8 (Use in Specific Populations). Genentech, Inc. accessdata.fda.gov Primary source for the terminal half-life (90–130 minutes), plasma clearance (99–119 mL/min), volume of distribution, hepatic clearance, body-weight covariate effects, geriatric data, and absence of paediatric and lactation data.