ACUTE ISCHEMIC STROKE
Tenecteplase
David Goldemund M.D.
Updated on 01/09/2024, published on 24/07/2024
Updated on 01/09/2024, published on 24/07/2024
Introduction
- tenecteplase (METALYSE) is a genetically modified form of tissue plasminogen activator (tPA) with increased resistance to PAI, greater fibrin specificity, and a longer half-life (17±7min), allowing for a single bolus administration
- historically, the term “tPA” has been used to refer to alteplase because it has long been the only tissue plasminogen activator in use
- nowadays, it is important to use the name of the specific agent instead
- tenecteplase appears to be a safe and effective alternative to alteplase for the treatment of acute ischemic stroke (AIS)
- recent studies and trials have shown its efficacy and potential benefits over the standard thrombolytic treatment with alteplase
- EXTEND-IA TNK showed a higher incidence of reperfusion and better functional outcome with TNK compared to alteplase in patients with large artery occlusion (LVO) followed by MT (complete reperfusion 22% with TNK vs. 10% with alteplase)
- ACT (2022) and ATTEST-2 (2023) showed non-inferiority of TNK at a dose of 0.25 mg/kg compared to alteplase in a standard indication
- meta-analysis of 4 RCTs in patients with LVO [Katsanos, 2020]
- advantages over alteplase:
- a single bolus administration is more convenient, reducing the complexity of care, especially in emergency settings
- generally, tenecteplase is less expensive than alteplase
Indications
| Indication | Dosage | Comments |
| stroke < 4.5 hours | 0.25 mg/kg | safe and effective alternative to alteplase with easier administration as a single bolus |
| 0.40 mg/kg | the higher dose is not recommended due to the potential increased risk of sICH and the lack of additional benefit | |
| stroke < 4.5 hours + large vessel occlusion (LVO) | 0.25 mg/kg | preferable over alteplase before mechanical thrombectomy (MT); higher reperfusion and better functional outcomes were observed |
| stroke on awakening or of unknown onset | 0.25 mg/kg | not recommended without advanced imaging for patient selection a reasonable alternative to alteplase for patients who are eligible for IVT after selection with advanced imaging (FLAIR-DWI mismatch or perfusion mismatch) |
Stroke onset ≤ 4.5 hours
- tenecteplase (TNK) 0.25 mg/kg can be used as a safe and effective alternative to alteplase 0.9 mg/kg
- tenecteplase at a dose of 0.40 mg/kg is not recommended (negative NOR-TEST 2 trial part A + in ExTEND-IA trial part 2, a dose of 0.40 mg/kg versus 0.25 mg/kg did not significantly improve reperfusion before MT)
- guidelines suggest favoring tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg for patients with acute ischaemic stroke in light of safety and efficacy data and because tenecteplase can be administered with a single bolus rather than a 1-hour infusion (ESO guidelines, 2023)
Stroke onset > 4.5 hours
- there are no hard data from trials, and this scenario is not discussed in recent ESO guidelines (2023)
- administration of tenecteplase (TNK) in such cases is off-label
- however, tenecteplase is suggested for WUS or stroke of unknown onset in selected patients based on advanced imaging; the same may apply for IVT beyond 4.5 hours (using the same imaging criteria as with alteplase)
Stroke onset ≤ 4.5h + large vessel occlusion (LVO)
- tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg is recommended
- patients with LVO who are directly admitted to a thrombectomy-capable center, IVT with tenecteplase 0.25 mg/kg or 0.40 mg/kg is suggested over skipping IVT (ESO guidelines 2023)
- patients with LVO who are admitted to a center without mechanical thrombectomy capability, tenecteplase 0.25 mg/kg followed by rapid transfer to a thrombectomy-capable center is recommended
Wake-up stroke (WUS)/unknown onset
- patients with AIS on awakening from sleep or stroke of unknown onset selected with non-contrast CT: tenecteplase 0.25 mg/kg outside the context of a clinical trial is not recommended
- tenecteplase 0.25 mg/kg could be a reasonable alternative to alteplase 0.9 mg/kg for patients who are eligible for IVT after selection with advanced imaging (FLAIR-DWI mismatch or perfusion mismatch as outlined in the 2021 ESO Guidelines on IVT) (expert consensus)
Contraindications and adverse events
- contraindications are same as for alteplase
- most common adverse events:
- bleeding, including intracranial hemorrhage
- allergic reactions
- hypotension
- nausea and vomiting
- fever
Administration, dosing
- the recommended dose for acute ischemic stroke is 0.25 mg/kg body weight, with a maximum dose of 25 mg
- the vial of tenecteplase (METALYSE) is diluted with the supplied solution
- each vial contains 10,000 units (50 mg) of tenecteplase, and each pre-filled syringe contains 10 mL of solvent ⇒ the reconstituted solution contains 1000 IU/5mg per 1mL
- the solution is administered as a single bolus injection over 5-10 seconds via a separate cannula (do not mix with other medications)
- after that, continuous monitoring for signs of bleeding, neurological assessments, and blood pressure monitoring should be conducted regularly
