View source for Tenecteplase

{{Short description|Pharmaceutical drug}}
{{more footnotes|date=September 2012}}
{{Use dmy dates|date=February 2025}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| verifiedrevid = 477861633
| image =
| alt = 

<!-- Clinical data -->
| pronounce         = 
| tradename = Tnkase
| Drugs.com = {{drugs.com|monograph|tenecteplase}}
| MedlinePlus       = a625007
| DailyMedID        = Tenecteplase
| pregnancy_AU      = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment = 
| pregnancy_category = 
| routes_of_administration = [[Intravenous]]
| class             = [[Tissue plasminogen activator]]
| ATC_prefix = B01
| ATC_suffix = AD11
| ATC_supplemental =  
| biosimilars       = 

<!-- Legal status -->
| legal_AU          = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment  = 
| legal_BR          = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C5, D1, D2, E, F1, F2, F3, F4 -->
| legal_BR_comment  = 
| legal_CA          = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment  = 
| legal_DE          = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment  = 
| legal_NZ          = <!-- Class A, B, C -->
| legal_NZ_comment  = 
| legal_UK          = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment  = 
| legal_US = Rx-only
| legal_US_comment = <ref name="Tnkase FDA label">{{cite web | title=Tnkase- tenecteplase kit | website=DailyMed | date=18 December 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=739a3c53-caf6-40d6-a6af-84ce733a948b | access-date=28 February 2025}}</ref><ref>{{cite web | title=Tnkase- tenecteplase kit | website=DailyMed | date=10 January 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e647640d-c395-4b4b-a0be-1162f9c21d84 | access-date=28 February 2025}}</ref>
| legal_EU          = 
| legal_EU_comment  = 
| legal_UN          = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment  = 
| legal_status = Rx-only

<!-- Pharmacokinetic data -->
| bioavailability   = 
| protein_bound     = 
| metabolism        = 
| metabolites       = 
| onset             = 
| elimination_half-life = 
| duration_of_action = 
| excretion = Liver

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 191588-94-0
| PubChem =  
| IUPHAR_ligand     = 
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00031
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = WGD229O42W
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02837
| ChEBI             = 
| ChEMBL            = 
| NIAID_ChemDB      = 
| PDB_ligand        = 
| synonyms          = 

<!-- Chemical and physical data -->
| IUPAC_name = Human tissue plasminogen activator
| C=2561 | H=3919 | N=747 | O=781 | S=40
}}

'''Tenecteplase''', sold under the brand name '''Tnkase''' among others, is an [[enzyme]] used as a [[thrombolytic drug]].<ref name="Tnkase FDA label" />

Tenecteplase is a [[tissue plasminogen activator]] (tPA) produced by [[recombinant DNA]] technology using an established mammalian cell line ([[Chinese hamster ovary|Chinese hamster ovary cells]]).<ref name="Tnkase FDA label" /> Tenecteplase is a 527 amino acid [[glycoprotein]] developed by introducing the following modifications to the [[complementary DNA]] for natural human tPA: a substitution of [[threonine]] 103 with [[asparagine]], and a substitution of asparagine 117 with [[glutamine]], both within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain.<ref name="Tnkase FDA label" />

Tenecteplase was approved for medical use in the United States in June 2000.<ref name="Tnkase FDA label" /><ref>{{cite web | title=Tenecteplase Product Approval Information | website=U.S. [[Food and Drug Administration]] (FDA) | date=3 November 2008 | url=https://www.fda.gov/cder/biologics/products/tenegen060200.htm | archive-url=https://web.archive.org/web/20090119110643/https://www.fda.gov/cder/biologics/products/tenegen060200.htm | archive-date=19 January 2009 | url-status=dead | access-date=28 February 2025}}</ref>

== Medical uses ==
Tenecteplase is [[indicated]] to reduce the risk of death associated with acute ST elevation myocardial infarction and acute ischemic stroke.<ref name="Tnkase FDA label" /><ref>{{cite web | title=FDA Roundup: March 4, 2025 | website=U.S. Food and Drug Administration | date=4 March 2025 | url=https://www.fda.gov/news-events/press-announcements/fda-roundup-march-4-2025 | archive-url=https://web.archive.org/web/20250306153018/https://www.fda.gov/news-events/press-announcements/fda-roundup-march-4-2025 | url-status=dead | archive-date=6 March 2025 | access-date=7 March 2025}}</ref>

== Pharmacokinetics ==
{{unreferenced section|date=March 2025}}

Distribution: approximates [[plasma volume]]

Metabolism: Primarily liver

Half-life elimination: Biphasic: Initial: 20–24 minutes; Terminal: 90–130 minutes

Excretion: Clearance: Plasma: 99–119 mL/minute

==Gallery==
{{unreferenced section|date=March 2025}}

{{Gallery
| width=300 |height=240
| File:TNK-tPA.gif
| Here is TNK-tPA. It is very similar to t-PA, but the glycosylation occurring in Kringle 1 is manipulated. The mutation T103N means that glycosylation occurs at that point. The mutation N117Q means that the high mannose sugar residue is absent at that point.
| File:T-PA 296-299.png
| In human t-PA, the amino acids at position 296–299 are [[lysine]], [[histidine]], and two [[arginine]]s.
| File:TNK-tPA 296-299.png
| In TNK-tPA, these amino acids have been replaced by four [[alanine]]s. This mutation is responsible for increased resistance to [[PAI-1]].
}}

==Research==
Researchers at Newcastle University in Australia say they have had a significant breakthrough in treating stroke patients using the commonly used drug.<ref>{{cite journal | vauthors = Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, O'Brien B, Bladin C, McElduff P, Allen C, Bateman G, Donnan G, Davis S, Levi C | display-authors = 6 | title = A randomized trial of tenecteplase versus alteplase for acute ischemic stroke | journal = The New England Journal of Medicine | volume = 366 | issue = 12 | pages = 1099–1107 | date = March 2012 | pmid = 22435369 | doi = 10.1056/NEJMoa1109842 | hdl-access = free | hdl = 1959.13/1039697 }}</ref> The findings were published in the New England Medical Journal. Though safety has been established through previous clinical trials, there is ongoing debate about whether this is an effective treatment for [[ischemic stroke]], and significant ongoing discussion between emergency physicians, neurologists and pharmacists about whether this treatment should be used for that indication.

The [[American Heart Association]]/American Stroke Association 2019 update to the 2018 guidelines for the Early Management of Acute Ischemic Stroke supports considering tenecteplase over [[alteplase]] in patients without contraindication to intravenous thrombolytics.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = 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 | journal = Stroke | volume = 50 | issue = 12 | pages = e344–e418 | date = December 2019 | pmid = 31662037 | doi = 10.1161/str.0000000000000211 | s2cid = 204973899 | doi-access = free }}</ref>

== References ==
{{reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Gurbel PA, Hayes K, Bliden KP, Yoho J, Tantry US | title = The platelet-related effects of tenecteplase versus alteplase versus reteplase | journal = Blood Coagulation & Fibrinolysis | volume = 16 | issue = 1 | pages = 1–7 | date = January 2005 | pmid = 15650539 | doi = 10.1097/00001721-200501000-00001 | s2cid = 44664652 }}
* {{cite journal | vauthors = Melzer C, Richter C, Rogalla P, Borges AC, Theres H, Baumann G, Laule M | title = Tenecteplase for the treatment of massive and submassive pulmonary embolism | journal = Journal of Thrombosis and Thrombolysis | volume = 18 | issue = 1 | pages = 47–50 | date = August 2004 | pmid = 15744554 | doi = 10.1007/s11239-004-0174-z | s2cid = 10947258 }}
* {{cite journal | vauthors = Ohman EM, Van de Werf F, Antman EM, Califf RM, de Lemos JA, Gibson CM, Oliverio RL, Harrelson L, McCabe C, DiBattiste P, Braunwald E | display-authors = 6 | title = Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction: results of a randomized trial | journal = American Heart Journal | volume = 150 | issue = 1 | pages = 79–88 | date = July 2005 | pmid = 16084152 | doi = 10.1016/j.ahj.2005.01.007 }}
* {{cite journal | vauthors = De Luca G, Suryapranata H, Chiariello M | title = Tenecteplase followed by immediate angioplasty is more effective than tenecteplase alone for people with STEMI. Commentary | journal = Evidence-Based Cardiovascular Medicine | volume = 9 | issue = 4 | pages = 284–287 | date = December 2005 | pmid = 16380055 | doi = 10.1016/j.ebcm.2005.09.021 }}
* {{cite journal | vauthors = | title = Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial | journal = Lancet | volume = 367 | issue = 9510 | pages = 569–578 | date = February 2006 | pmid = 16488800 | doi = 10.1016/S0140-6736(06)68147-6 | s2cid = 23972378 }}
* {{cite journal | vauthors = Bozeman WP, Kleiner DM, Ferguson KL | title = Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions | journal = Resuscitation | volume = 69 | issue = 3 | pages = 399–406 | date = June 2006 | pmid = 16563599 | doi = 10.1016/j.resuscitation.2005.09.027 }}
* {{cite journal | vauthors = Hull JE, Hull MK, Urso JA, Park HA | title = Tenecteplase in acute lower-leg ischemia: efficacy, dose, and adverse events | journal = Journal of Vascular and Interventional Radiology | volume = 17 | issue = 4 | pages = 629–636 | date = April 2006 | pmid = 16614145 | doi = 10.1097/01.RVI.0000202751.74625.79 }}
* {{cite journal | vauthors = Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, O'Brien B, Bladin C, McElduff P, Allen C, Bateman G, Donnan G, Davis S, Levi C | display-authors = 6 | title = A randomized trial of tenecteplase versus alteplase for acute ischemic stroke | journal = The New England Journal of Medicine | volume = 366 | issue = 12 | pages = 1099–1107 | date = March 2012 | pmid = 22435369 | doi = 10.1056/NEJMoa1109842 | hdl-access = free | hdl = 1959.13/1039697 }}
{{refend}}

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[[Category:Antithrombotic enzymes]]
[[Category:Drugs developed by Hoffmann-La Roche]]
[[Category:Drugs developed by Genentech]]
[[Category:Fibrinolytic enzymes]]