Tenecteplase Explained

Tenecteplase, sold under the trade names TNKase, Metalyse and Elaxim, is an enzyme used as a thrombolytic drug.

Tenecteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established mammalian cell line (Chinese hamster ovary cells). 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.

Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA.

The abbreviation TNK is common for referring to tenecteplase, but abbreviating drug names is not best practice in medicine, and in fact "TNK" is one of the examples given on the Institute for Safe Medication Practices do-not-use list.

Research

Researchers at Newcastle University in Australia say they have had a significant breakthrough in treating stroke patients using the commonly used drug.^[1] 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.^[2]

Pharmacokinetics

Distribution: approximates plasma volume

Metabolism: Primarily hepatic

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

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

Further reading

• Gurbel PA, Hayes K, Bliden KP, Yoho J, Tantry US . The platelet-related effects of tenecteplase versus alteplase versus reteplase . Blood Coagulation & Fibrinolysis . 16 . 1 . 1–7 . January 2005 . 15650539 . 10.1097/00001721-200501000-00001 . 44664652 .
• Melzer C, Richter C, Rogalla P, Borges AC, Theres H, Baumann G, Laule M . Tenecteplase for the treatment of massive and submassive pulmonary embolism . Journal of Thrombosis and Thrombolysis . 18 . 1 . 47–50 . August 2004 . 15744554 . 10.1007/s11239-004-0174-z . 10947258 .
• 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 . 6 . Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction: results of a randomized trial . American Heart Journal . 150 . 1 . 79–88 . July 2005 . 16084152 . 10.1016/j.ahj.2005.01.007 .
• De Luca G, Suryapranata H, Chiariello M . Tenecteplase followed by immediate angioplasty is more effective than tenecteplase alone for people with STEMI. Commentary . Evidence-Based Cardiovascular Medicine . 9 . 4 . 284–287 . December 2005 . 16380055 . 10.1016/j.ebcm.2005.09.021 .
• Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial . Lancet . 367 . 9510 . 569–578 . February 2006 . 16488800 . 10.1016/S0140-6736(06)68147-6 . 23972378 .
• Bozeman WP, Kleiner DM, Ferguson KL . Empiric tenecteplase is associated with increased return of spontaneous circulation and short term survival in cardiac arrest patients unresponsive to standard interventions . Resuscitation . 69 . 3 . 399–406 . June 2006 . 16563599 . 10.1016/j.resuscitation.2005.09.027 .
• Hull JE, Hull MK, Urso JA, Park HA . Tenecteplase in acute lower-leg ischemia: efficacy, dose, and adverse events . Journal of Vascular and Interventional Radiology . 17 . 4 . 629–636 . April 2006 . 16614145 . 10.1097/01.RVI.0000202751.74625.79 .
• Web site: Stroke patients make 'Lazarus-like' recovery . The World Today . Peacock M . 22 March 2012 .
• 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 . 6 . A randomized trial of tenecteplase versus alteplase for acute ischemic stroke . The New England Journal of Medicine . 366 . 12 . 1099–1107 . March 2012 . 22435369 . 10.1056/NEJMoa1109842 . free . 1959.13/1039697 .

Notes and References

1. 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 . 6 . A randomized trial of tenecteplase versus alteplase for acute ischemic stroke . The New England Journal of Medicine . 366 . 12 . 1099–1107 . March 2012 . 22435369 . 10.1056/NEJMoa1109842 . free . 1959.13/1039697 .
2. 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 . 6 . 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 . 50 . 12 . e344–e418 . December 2019 . 31662037 . 10.1161/str.0000000000000211 . 204973899 . free .