What is the Difference Between Alteplase and Tenecteplase

The main difference between alteplase and tenecteplase is that intravenous alteplase is a tissue plasminogen activator, which is the only approved treatment for acute ischemic stroke, whereas tenecteplase is a genetically-engineered, mutant tissue plasminogen activator, which is an alternative thrombolytic agent. However, tenecteplase is more fibrin-specific and has longer activity than alteplase. Furthermore, alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke while tenecteplase is given as a bolus and may increase the incidence of vascular reperfusion.  

Alteplase and tenecteplase are two types of thrombolytic drugs used prior to thrombectomy in ischemic strokes to reperfuse ischemic areas of the brain.   

Key Areas Covered 

1. What is Alteplase
     – Definition, Origin, Importance
2. What is Tenecteplase
     – Definition, Origin, Importance
3. What are the Similarities Between Alteplase and Tenecteplase
     – Outline of Common Features
4. What is the Difference Between Alteplase and Tenecteplase
     – Comparison of Key Differences

Key Terms 

Acute Ischemic Stroke (AIS), Alteplase, Tenecteplase, Thrombolytic Drugs, Tissue Plasminogen Activator

Difference Between Alteplase and Tenecteplase - Comparison Summary

What is Alteplase 

Alteplase is a thrombolytic drug primarily used to treat acute ischemic stroke (AIS), acute myocardial infarction as well as acute massive pulmonary embolism. Significantly, the patients are eligible for the treatment within 4.5 hours of ischemic stroke onset. Generally, AIS is a high mortality and high disability disease. Moreover, it is the most common stroke subtype, life-threatening illness.

Difference Between Alteplase and Tenecteplase

Figure 1: T-PA Pathway

Furthermore, alteplase is a second-generation drug. However, as it is a tissue plasminogen activator, it selectively activates fibrin-bound plasminogen to convert into plasmin, facilitating thrombolysis and recanalizing the occluded blood vessels. It is also a serine protease, and it binds fibrin in a thrombus at the systemic circulation, initiating thrombolysis. However, there are some limitations to alteplase. They include low recanalization rate, the risk of bleeding, especially intracranial hemorrhage (ICH), the requirement of continuous infusion, short half-life, etc.  

What is Tenecteplase 

Tenecteplase is a genetically-modified tissue plasminogen activator designed for better safety and efficacy when compared to alteplase. Basically, it is a 527 amino acid long glycoprotein with introduced modifications to the natural human tissue plasminogen factor (t-PA). These modifications include a substitution of threonine 103 with asparagine, and a substitution of asparagine 117 with glutamine within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain. Also, it is  third-generation fibrinolytic agent. 

Alteplase vs Tenecteplase

Figure 2: Human T-PA

Furthermore, the main features of tenecteplase are the higher fibrin specificity, longer free plasma half-life, and the ability to administrate at faster rates. Additionally, it shows greater resistance to inactivation by plasminogen activator inhibitor-1 and no procoagulant effects. Therefore, these pharmacodynamic differences between alteplase and tenecteplase cause rapid and complete reperfusion, reducing the risk of ICH.  

Similarities Between Alteplase and Tenecteplase 

  • Alteplase and tenecteplase are thrombolytic two drugs used prior to endovascular thrombectomy in ischemic strokes to reperfuse ischemic areas of the brain.  
  • Moreover, they are used for the intravenous thrombolysis. 
  • They are given for large-vessel occlusion of the internal carotid, middle cerebral, or basilar artery. 
  • Both are tissue plasminogen activators. 
  • Both are administrated intravenously within 4.5 hours after symptom onset.   
  • Their mechanism of action is to selectively bind to the fibrin component of the thrombus to convert thrombus-bound plasminogen to plasmin, degrading the fibrin matrix of the thrombus.  
  • Furthermore, their secondary outcomes include the modified Rankin scale score at 90 days.   
  • Their safety outcomes include death and symptomatic intracerebral hemorrhage.  
  • Besides, both drugs lead to a lower incidence of systemic hemorrhage. 

Difference Between Alteplase and Tenecteplase 


Alteplase refers to a thrombolytic drug used to treat acute myocardial infractions and other severe conditions caused by breaking up the blood clots while tenecteplase refers to a recombinant enzyme used as a thrombolytic drug. Thus, this is the main difference between alteplase and tenecteplase.

Trade Names 

The trade names of alteplase are Activase and Actilyse, and the trade names of tenecteplase are TNKase and Metalyse. 


Alteplase is a tissue plasminogen activator while tenecteplase is a recombinant tissue plasminogen activator produced using an established mammalian cell line. 


The regular dose of alteplase is 0.9 mg/kg, while the dose of tenecteplase is 0.25 mg/kg. (This is only a piece of basic information, not a prescription)

Maximum Dose 

The maximum dose of alteplase is 90 mg, while the maximum dose of tenecteplase is 25 mg. (This is only a piece of basic information, not a prescription)

Method of Administration 

Alteplase is given as an infusion over a period of approximately 1 hour while tenecteplase is given as a bolus; administration at faster rates. 

Incidence of Vascular Reperfusion  

Incidence of vascular reperfusion is low with alteplase, while the incidence of vascular reperfusion is high with tenecteplase. 

90-Day Functional Outcome  

The 90-day functional outcome is good with alteplase, while the 90-day functional outcome is better with tenecteplase. 

Early Major Neurological Improvement   

Alteplase shows a good early major neurological improvement while tenecteplase shows a significantly better early major neurological improvement. 

Fibrin Specificity 

Moreover, Alteplase is less fibrin-specific while tenecteplase is more fibrin-specific. 


Alteplase has a comparatively a shorter half-life while tenecteplase has a longer half-life. 

Inactivation by Alteplase Inhibitors  

Also, another difference between alteplase and tenecteplase is that Alteplase is inactivated by alteplase inhibitors, while tenecteplase is not inactivated by alteplase inhibitors. 

Intracranial Hemorrhage 

Alteplase has an increased risk of intracranial hemorrhage, while tenecteplase has a reduced risk of intracranial hemorrhage. 


Alteplase is more expensive than tenecteplase. 


Alteplase is the conventional thrombolytic drug used prior to endovascular thrombectomy and thrombolysis in ischemic strokes. Also, it is a tissue plasminogen activator. On the other hand, tenecteplase is a genetically-modified form of alteplase. Significantly, it shows high fibrin-specificity, longer half-life, safety, and efficacy when compared to alteplase. Therefore, the main difference between alteplase and tenecteplase is the characteristics of drugs. 


1. Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, et al. “Tenecteplase versus Alteplase for Acute Ischemic Stroke.” New England Journal of Medicine, vol. 367, no. 3, 2012, pp. 275–276., doi:10.1056/nejmc1205829.
2. Xu, Na, et al. “Different Doses of Tenecteplase vs Alteplase in Thrombolysis Therapy of Acute Ischemic Stroke: Evidence from Randomized Controlled Trials.” Drug Design, Development and Therapy, Volume 12, 2018, pp. 2071–2084., doi:10.2147/dddt.s170803.

Image Courtesy:

1. “Tpa pathways” By Djain2 – Own work (CC BY-SA 4.0) via Commons Wikimedia   
2. “T-PA” By MedicineFTWq – Own work (CC BY-SA 4.0) via Commons Wikimedia   

About the Author: Lakna

Lakna, a graduate in Molecular Biology and Biochemistry, is a Molecular Biologist and has a broad and keen interest in the discovery of nature related things. She has a keen interest in writing articles regarding science.

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