Tenecteplase

50mg lyophilized powder (IV)

Dosing Summary

Acute Myocardial Infarction with ST elevation (STEMI <12hrs)

FDA approved, 2000. Indicated when anticipated STEMI diagnosis to Percutaneous Coronary Intervention-mediated reperfusion time is >120min.

Adult dose (IV ,bolus):

  • <60 kg 30mg

  • 60 - 69 kg 35mg

  • 70 - 79 kg 40mg

  • 80 - 89 kg 45mg

  • ≥90 kg 50mg

Acute Ischemic Stroke (AIS <4.5hrs)

Not FDA approved.

Adult dose (IV ,bolus):

  • AIS eligible for mechanical thrombectomy

    • 0.25mg/kg bolus (max 25mg)

  • AIS with minor neurological impairment uneligible for a mechanical thrombectomy

    • 0.4mg/kg bolus

Pulmonary Embolism (PE)

Not FDA approved. Prefer alteplase for PE fibrinolytic therapy. If unavailable, consider tenecteplase.

Adult dose (IV, bolus):

  • <60 kg 30mg

  • 60 - 69 kg 35mg

  • 70 - 79 kg 40mg

  • 80 - 89 kg 45mg

  • ≥90 kg 50mg

Emergency Medicine Executive Summary

(Summary Version, Updated August 2021)

Emergency Medicine Executive Summary

Tenecteplase (TNK) is a modified form of the Tissue Plasminogen Activator alteplase, with enhanced fibrin affinity, diminished fibrinogenolysis (greater fibrin-specificity) and Plasminogen Activator Inhibitor-1 (PAI-1) resistance (1). These properties prolong its half-life permitting administration as a single bolus which is remarkably useful in emergency medicine.

FDA and EMA approved its use only for emergency reperfusion in Acute Myocardial Infarction with ST elevation (STEMI)(1, 2). Compared to alteplase, it is safer due to a lower risk of non-cerebral hemorrhage and blood transfusion (13), and is easier to administer. Those advantages led TNK as the fibrinolytic of choice in STEMI (3).

In the past decade tenecteplase has been studied to treat Acute Ischemic Stroke (AIS) with promising results (5, 7, 8, 17). Although this drug has not yet been universally adopted for the treatment of AIS, there are relevant data that favor it:

  • Several randomized controlled trials (eg. 7, 17) and systematic reviews with meta-analyzes (eg. 8) show no-inferiority between tenecteplase and alteplase, as well as no differences in intracranial bleeding rates.

  • Based on these studies and other important literature, the latest guidelines from the American Stroke Association recommend its use as an alternative to alteplase (3).

Therefore, the use of TNK for AIS is steadily increasing among clinicians beyond research purposes; for example in 2016 tenecteplase was approved to treat AIS by the Indian health authorities (9).

EMDrugs do not encourage its use for Pulmonary Embolism because there are no solid comparative studies of tenecteplase vs alteplase in high-risk PE (hemodynamic instability). Interestingly, when tenecteplase is compared with alteplase for PE, TNK is associated with an increased risk of major bleeding, but in myocardial infarction, the data show a reduced risk of major bleeding (10, 13). This increased risk is known to be related to the older population (significantly higher risk in patients >65 years)(11), and is probably associated with concomitant heparin administration (eg. PEITHO trial protocol)(16).

Always consider the contraindications seriously and balance the risk of tenecteplase fibrinolysis of intracranial hemorrhage and other major bleeding events versus the benefit of the therapy. This intervention must be decided -or at least supported- by a specialist (eg. emergency medicine, neurologist, cardiologist, intensivist).

Contraindications to systemic fibrinolytic therapy

There isn't a definite and universally accepted list of contraindications, and it seems to be a tendency to become simpler over the years. Beware that references differ on some issues.

Absolute contraindications (3, 4)

  • Previous intracranial haemorrhage or stroke of unknown origin at any time

  • Ischemic stroke in the preceding 6 months (except in AIS <4,5h indication)

  • Central nervous system damage or neoplasms or arteriovenous malformation

  • Recent major trauma / surgery / head injury (within the preceding month)

  • Gastrointestinal bleeding within the past month

  • Known bleeding disorder (excluding menses)

  • Aortic dissection

  • Non-compressible punctures in the past 24 hours (e.g. liver biopsy, lumbar puncture)

  • Active internal bleeding

Relative contraindications (3, 4)

  • Transient ischemic attack in the preceding 6 months

  • Oral anticoagulant therapy

  • Pregnancy or within 1 week postpartum

  • Refractory hypertension (SBP >180mmHg and/or DBP >110 mmHg)

  • Advanced liver disease

  • Infective endocarditis

  • Active peptic ulcer

  • Prolonged or traumatic resuscitation

Adult dose

  • Acute Myocardial Infarction with ST elevation (STEMI <12 hours)

FDA approval in 2000. EMA approval in 2001. Indicated when anticipated STEMI diagnosis to Percutaneous Coronary Intervention-mediated reperfusion time is >120min (3).

Relevant studies: ASSENT trial, 1999 (13).

Adult dose (IV ,bolus):

  • <60 kg 30mg

  • 60 - 69 kg 35mg

  • 70 - 79 kg 40mg

  • 80 - 89 kg 45mg

  • ≥90 kg 50mg

  • Acute Ischemic Stroke (AIS <4.5 hours)
    Not FDA approved. Recent guidelines support usage as an alternative to alteplase (4).

Studied schemes in AIS have been conducted with 0.1, 0.25 and 0.4mg/kg, possibly 0.25mg/kg is the safer and equally effective dose, but more data is needed to reassure this (15).
Adult dose based on latest AHA/ASA Guidelines For the Early Management of Acute Ischemic Stroke 2018/2019 (4):

  • AIS in patients eligible to undergo mechanical thrombectomy (7):

  • 0.25mg/kg IV bolus (max 25mg)

  • AIS with minor neurological impairment and no major intracranial occlusion (17):

    • 0.4mg/kg IV bolus

  • Pulmonary Embolism
    Not FDA approved. Prefer alteplase If alteplase is unavailable, consider same tenecteplase dose used for myocardial infarction:

Adult dose (IV, bolus):

  • <60 kg 30mg

  • 60 - 69 kg 35mg

  • 70 - 79 kg 40mg

  • 80 - 89 kg 45mg

  • ≥90 kg 50mg

Pediatric dose

Efficacy and safety not established. Pediatric tenecteplase usage data derives mostly from case reports limited to dysfunctional central venous catheters (12).


Prefer alteplase for fibrinolytic therapy.

References

  1. EMA (European Medicines Agency), Metalyse: EPAR (European Public Assessment Report) - Product Information. First published 2009, Last updated March 2021. Visited in August 2021.
    EMA

  2. US FDA (United States Food and Drug Administration) CDER (Center for Drug Evaluation and Research), Tenecteplase Product Approval Information - Licencing Action, Department of Health and Human Services, June 2, 2000.
    US-FDA

  3. Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-177. doi:10.1093/eurheartj/ehx393.
    Pubmed

  4. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association [published correction appears in Stroke. 2018 Mar;49(3):e138] [published correction appears in Stroke. 2018 Apr 18;:]. Stroke. 2018;49(3):e46-e110. doi:10.1161/STR.0000000000000158.
    Pubmed

  5. Powers WJ. Acute Ischemic Stroke. N Engl J Med. 2020;383(3):252-260. doi:10.1056/NEJMcp1917030.
    Pubmed

  6. Kheiri B, Osman M, Abdalla A, et al. Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials. J Thromb Thrombolysis. 2018;46(4):440-450. doi:10.1007/s11239-018-1721-3.
    Pubmed

  7. NOR-TEST - Logallo N, Novotny V, Assmus J, et al. Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial. Lancet Neurol. 2017;16(10):781-788. doi:10.1016/S1474-4422(17)30253-3.
    Pubmed

  8. Burgos AM, Saver JL. Evidence that Tenecteplase Is Noninferior to Alteplase for Acute Ischemic Stroke: Meta-Analysis of 5 Randomized Trials. Stroke. 2019;50(8):2156-2162. doi:10.1161/STROKEAHA.119.025080.
    Pubmed

  1. National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases & Stroke (NPCDCS) Guidelines for Prevention and Management of Stroke Directorate General of Health Services Ministry of Health and Family Welfare Government of India. 2019.
    Ministry Of Health & Family Welfare - Government of India

  2. Marti C, John G, Konstantinides S, et al. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J. 2015;36(10):605-614. doi:10.1093/eurheartj/ehu218.
    Pubmed

  3. Chatterjee S, Chakraborty A, Weinberg I, et al. Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis. JAMA. 2014;311(23):2414-2421. doi:10.1001/jama.2014.5990.
    Pubmed

  4. Tebbi C, Costanzi J, Shulman R, et al. A phase III, open-label, single-arm study of tenecteplase for restoration of function in dysfunctional central venous catheters. J Vasc Interv Radiol. 2011;22(8):1117-1123. doi:10.1016/j.jvir.2011.02.034.
    Pubmed

  5. ASSENT-2 - Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Investigators, Van De Werf F, Adgey J, et al. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet. 1999;354(9180):716-722. doi:10.1016/s0140-6736(99)07403-6.
    Pubmed

  6. NIH-NLM (National Institutes of Health National Library of Medicine). DailyMed. Label: TNKASE tenecteplase kit. Updated in December 2019. Visited in August 2021.
    DailyMed

  1. Zitek T, Ataya R, Brea I. Using Tenecteplase for Acute Ischemic Stroke: What Is the Hold Up?. West J Emerg Med. 2020;21(2):199-202. Published 2020 Feb 24. doi:10.5811/westjem.2020.1.45279.
    Pubmed

  2. PEITHO - Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med. 2014;370(15):1402-1411. doi:10.1056/NEJMoa1302097.
    Pubmed

  3. EXTEND-IA TNK Part 2 - Campbell BCV, Mitchell PJ, Churilov L, et al. Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial. JAMA. 2020;323(13):1257-1265. doi:10.1001/jama.2020.1511.
    Pubmed

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