Tenecteplase versus Alteplase for ischemic stroke

As a hospital pharmacist, you'll hear about more hospitals switching from alteplase (Activase) to tenecteplase (TNKase) to treat acute ischemic stroke. Tenecteplase is easier to give. It's a single IV push, due to its longer half-life rather than a bolus plus 1-hour infusion for alteplase. This may also speed up transfers for patients who need thrombectomy. And Tenecteplase with lower cost and a more favourable pharmacokinetic profile.

Compared to alteplase, using tenecteplase within 4.5 hours of stroke symptoms seems to have similar rates of neurological and functional improvement, mortality and intracranial hemorrhage. But most comparison trials are small and open-label. And the best tenecteplase data are in patients with a large vessel occlusion who are eligible for thrombectomy. Alteplase has more evidence overall. Plus the manufacturer replaces unused, reconstituted vials of alteplase, BUT not tenecteplase, since use in stroke is off-label.

     Ensure a safe transition if your hospital shifts to tenecteplase. Apply similar inclusion and exclusion criteria as alteplase. Limit tenecteplase to patients presenting within 4.5 hours of symptom onset. Ongoing studies will address use outside this window.

Ensure correct dosing. Tenecteplase is 0.25 mg/kg up to 25 mg for stroke. Acute MI or pulmonary embolism doses are higher. And it comes as a 50 mg vial, in a kit with MI dosing printed under the box lid. After the dose, monitor similar to alteplase. Watch for neuro changes AND maintain blood pressure less than 180/105 mmHg and stay alert for rare angioedema. If alteplase is kept for other indications (catheter-directed thrombolysis, etc), avoid errors by using separate storage, labels, etc.

Tenecteplase (TNKase), intravenous (off-label)
Consider for… Dose Comments
Patients without contraindications to IV fibrinolysis who are also eligible for mechanical thrombectomy (lower dose; reasonable to choose over alteplase).

Patients with minor neurological impairment (e.g., NIHSS score 4) and no major intracranial occlusion (higher dose).
Lower dose: 0.25 mg/kg, (max 25 mg) as an IV bolus.

Or

Higher dose: 0.4 mg/kg as an IV bolus.

Note: Incompatible with dextrose. Flush dextrose-containing line with saline before and after administration.
Long duration of action and fibrin specificity allows a single bolus dose, which can avoid delays in interhospital transfer.

Cheaper and likely more cost-effective than alteplase.

Safety similar to IV alteplase, but not shown to be superior.

In patients with large vessel occlusion, in an open-label study, tenecteplase was associated with greater reperfusion pre-thrombectomy than alteplase.

Tenecteplase and alteplase seem to provide similar neurologic and functional outcomes (per modified Rankin scale) and mortality, with a similar rate of intracranial hemorrhage. However, there is more evidence overall for use of alteplase.

Joint Commission appears to accept it as an alteplase alternative for its thrombolytic therapy performance measure.
The higher dose has not been proven superior or noninferior to alteplase.

REFERENCES

  • Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Bailey P, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater LA, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Investigators. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018 Apr 26;378(17):1573-1582. Available at: https://www.nejm.org/doi/10.1056/NEJMoa1716405?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov

    Burgos AM, Saver JL. Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke: Meta-Analysis of 5 Randomized Trials. Stroke. 2019 Aug;50(8):2156-2162. Available at: https://pubmed.ncbi.nlm.nih.gov/31318627

    Oliveira M, Fidalgo M, Fontão L, Antão J, Marques S, Afreixo V, Gregório T. Tenecteplase for thrombolysis in stroke patients: Systematic review with meta-analysis. Am J Emerg Med. 2021 Apr;42:31-37. Available at: https://pubmed.ncbi.nlm.nih.gov/33440328

    Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. 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: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. Available at: https://pubmed.ncbi.nlm.nih.gov/31662037

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