Tenecteplase

Tenecteplase

Clinical data
Trade names	Metalyse
AHFS/Drugs.com	Monograph
MedlinePlus	a625007
License data	US DailyMed: Tenecteplase
Routes of administration	Intravenous
Drug class	Tissue plasminogen activator
ATC code	B01AD11 (WHO)
Legal status
Legal status	US: ℞-onlyTemplate:Infobox drug/non-ref-space In general: ℞ (Prescription only)
Pharmacokinetic data
Excretion	Liver
Identifiers
IUPAC name Human tissue plasminogen activator
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Chemical and physical data
Formula	C2561H3919N747O781S40
Molar mass	58951.37 g·mol−1
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Data page
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Tenecteplase, sold under the brand name Metalyse among others, 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 was approved for medical use in the United States in June 2000.

Medical uses

Tenecteplase is indicated to reduce the risk of death associated with acute ST elevation myocardial infarction and acute ischemic stroke.

Pharmacokinetics

The initial volume of distribution approximates plasma volume.

Tenecteplase is primarily metabolised through the liver.

Elimination is biphasic, with an initial half-life of 20–24 minutes and a terminal half-life of 90–130 minutes. Average plasma clearance ranges from 99–119 mL/minute.

Research

Researchers at Newcastle University in Australia say they have had a significant breakthrough in treating stroke patients using the commonly used drug. The findings were published in the New England Journal of Medicine. 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.

Further reading

• Gurbel PA, Hayes K, Bliden KP, Yoho J, Tantry US (January 2005). "The platelet-related effects of tenecteplase versus alteplase versus reteplase". Blood Coagulation & Fibrinolysis. 16 (1): 1–7. doi:10.1097/00001721-200501000-00001. PMID 15650539. S2CID 44664652.
• Melzer C, Richter C, Rogalla P, Borges AC, Theres H, Baumann G, et al. (August 2004). "Tenecteplase for the treatment of massive and submassive pulmonary embolism". Journal of Thrombosis and Thrombolysis. 18 (1): 47–50. doi:10.1007/s11239-004-0174-z. PMID 15744554. S2CID 10947258.
• Ohman EM, Van de Werf F, Antman EM, Califf RM, de Lemos JA, Gibson CM, et al. (July 2005). "Tenecteplase and tirofiban in ST-segment elevation acute myocardial infarction: results of a randomized trial". American Heart Journal. 150 (1): 79–88. doi:10.1016/j.ahj.2005.01.007. PMID 16084152.
• De Luca G, Suryapranata H, Chiariello M (December 2005). "Tenecteplase followed by immediate angioplasty is more effective than tenecteplase alone for people with STEMI. Commentary". Evidence-Based Cardiovascular Medicine. 9 (4): 284–287. doi:10.1016/j.ebcm.2005.09.021. PMID 16380055.
• "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. doi:10.1016/S0140-6736(06)68147-6. PMID 16488800. S2CID 23972378.
• Bozeman WP, Kleiner DM, Ferguson KL (June 2006). "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. doi:10.1016/j.resuscitation.2005.09.027. PMID 16563599.
• Hull JE, Hull MK, Urso JA, Park HA (April 2006). "Tenecteplase in acute lower-leg ischemia: efficacy, dose, and adverse events". Journal of Vascular and Interventional Radiology. 17 (4): 629–636. doi:10.1097/01.RVI.0000202751.74625.79. PMID 16614145.
• Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, et al. (March 2012). "A randomized trial of tenecteplase versus alteplase for acute ischemic stroke". The New England Journal of Medicine. 366 (12): 1099–1107. doi:10.1056/NEJMoa1109842. hdl:1959.13/1039697. PMID 22435369.