The Case to Replace Alteplase
/This lecture was presented at the 2021 Maine Medical Center Winter Symposium. For more information on the symposium click here.
Pharmacological differences between alteplase and tenecteplase:
Alteplase (tPA) is a recombinant version of naturally occurring enzyme called tissue plasminogen activator.
Tenecteplase (TNK) is a bioengineered variant of tPA to make it a better lytic by increasing its specificity to fibrin and more resistant to degradation by endogenous enzymes.
Half-life:
TNK: Initial: 20–24 minutes; Terminal: 90–130 minutes
tPA: Initial: 5 minutes; Terminal: 72 minutes
TNK’s greater fibrin specificity may mean fewer bleeding complications.
TNK’s longer half-life may mean better clot lysis.
TNK is easier to prepare and administer (a rapid, single-bolus) which may mean faster door-to-needle times and faster door-in-door-out times for transport (and hopefully translate into less disability after stroke).
created by JoLeen Bierlein, PharmD, BCPS
Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke: Meta-Analysis of 5 Randomized Trials. Stroke. 2019;50:2156-2162
Data Results Summary:
Efficacy: TNK has consistently been shown to have equal or better rates of recanalization and reperfusion compared with tPA and TNK has consistently shown to have equal or better clinical outcomes compared with tPA
Safety: TNK has consistently been shown to have equal or fewer intracranial hemorrhages compared with tPA. I have not seen any reports of TNK-associated angioedema in the literature, but theoretically, this could occur.
AHA/ASA Guidelines:
2018: “Tenecteplase administered as a 0.4-mg/kg single IV bolus has not been proven to be superior or noninferior to alteplase but might be considered as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion.” (based on the NOR-TEST trial)
2019 Update: “It may be reasonable to choose tenecteplase (single IV bolus of 0.25-mg/kg, maximum 25 mg) over IV alteplase in patients without contraindications for IV fibrinolysis who are also eligible to undergo mechanical thrombectomy.” (based on the EXTEND-IA TNK trial)
created by JoLeen Bierlein, PharmD, BCPS
Addressing common concerns:
Is the eligibility criteria for TNK different?
Eligibility for TNK is identical to the eligibility criteria for tPA.
How do I reverse bleeding complications with TNK?
Reversal of bleeding complications with TNK is identical to tPA reversal.
Is it expensive?
The cost of TNK is currently less than tPA.
Will payment for the use of TNK be denied because it is “off label?”
There are no issues with reimbursement for off-label use of any medication, including TNK.
Is it harder to prepare than tPA?
TNK requires less pharmacist/nursing time as it is easier and faster to prepare and administer.
Is there reimbursement for TNK like there is for tPA?
There is no reimbursement for unused TNK, however, given that ordering to administration can take less than 5 minutes, it is less likely for there to be a change in the decision to administer the lytic.
Jane Morris, MD
Tables by created by JoLeen Bierlein, PharmD, BCPS
Associate Professor of Emergency Medicine, Maine Medical Center
Edited and Posted by Jeffrey A. Holmes, MD
References
EXTEND-IA TNK Part2 NEJM. 2018;378:1573-82 [Full Article]
Burgos et al. Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke: Meta-Analysis of 5 Randomized Trials. Stroke. 2019 Aug;50(8):2156-2162.[Full Print]
