Tenecteplase Injection (TNKase — Genentech, Inc.)
January 15, 2001 3 minutes read
Pharmacology Update
Tenecteplase Injection (TNKase—Genentech, Inc.)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
The fda has approved tenecteplase, a new single bolus thrombolytic for the treatment of acute myocardial infarction (AMI). Tenecteplase is a modified tissue plasminogen activator produced by recombinant DNA technology using Chinese Ovary cells. Genentech has modified its other thrombolytic, human tissue plasminogen activator (tPA), to create the new agent. The changes result in a 527 amino acid glycoprotein with a lower plasma clearance and more fibrin specificity allowing it to be administered in a single bolus over 5 seconds.
Tenecteplase is marketed as TNKase by Genentech.
Indications
Tenecteplase is indicated for use in the reduction of mortality associated with AMI.1
Dosage
The dose of tenecteplase is based on body weight: 30 mg for patients less than 60 kg; 35 mg for those 60 kg or more, but less than 70 kg; 40 mg for patients 70 kg or more, but less than 80 kg; 45 mg for patients 80 kg or more, but less than 90 kg; and 50 mg for those 90 kg or more. The single intravenous bolus dose should be administered over 5 seconds and should be initiated as soon as possible after the onset of AMI symptoms.1
Tenecteplase is supplied as 50 mg lyophilized powder with 10 mL sterile water for injection.
Potential Advantages
The primary advantage of tenecteplase is its ease of administration. It can be given as a single bolus dose over 5 seconds compared to alteplase (rtPA), which requires a loading bolus and infusion over 1.5 hours, and reteplase, which requires two bolus doses 30 minutes apart. In a large (n =16,949), multicenter comparative trial, Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2), the frequency of noncerebral major bleeding was lower with tenecteplase compared to alteplase (4.68% vs 5.94%; P = 0.0002).2 The frequency of transfusion was also lower (4.25% vs 5.49%; P = 0.0002).
Potential Disadvantages
As with other agents, the primary disadvantage of thrombolytic therapy is the risk of stroke. In the ASSENT-2 trial, the stroke rates were 1.78% with a rate of 0.9% for intracranial hemorrhage. These rates were comparable to that seen with alteplase, 1.66% and 0.94%. The rate of ischemic stroke was slightly higher with tenecteplase but not statistically different from altepase (0.72% vs 0.64%).2
Comments
Tenecteplase is a mutant of human tissue plasminogen activator. The alteration by recombinant DNA technology results in a molecule with a longer plasma half-life (20 min vs 4 min), greater fibrin specificity, and more resistance to inhibition by plasminogen-activator inhibitor-1 compared to alteplase.3 In the ASSENT-2 trial, tenecteplase was comparable to alteplase in 30-day mortality. ASSENT-2 was a multicenter, double-blind, randomized, controlled trial involving 16,949 patients with AMI of less than six hours with a median time of onset to treatment of 2.8 hours. Patients received 30-50 mg of tenecteplase over 5-10 seconds, depending on weight, or up to 100 mg of alteplase by rapid infusion. All patients received aspirin and heparin. Heparin was titrated to a target activated partial thromboplastin time of 50-75 seconds for 48-72 hours. The 30-day mortality was 6.18% with tenecteplase and 6.15% with alteplase. The overall rate of mortality or nonfatal stroke was 7.11% with tenecteplase and 7.04% with alteplase (relative risk of 1.01 [95% CI 0.91-1.13]). Subgroup analysis revealed that patients whose time to treatment was longer than four hours seemed to fare better with tenecteplase than alteplase (7.0% mortality vs 9.2%; P = 0.018). The ASSENT-2 investigators suggest that the higher fibrin specificity of tenecteplase may lead to better dissolution of older fibrin clots.2 However, this subgroup represented only 22% of the study population. Overall, there was no difference in 30-day mortality. Patients who received treatment within 2-4 hours, representing the largest subgroup at 47%, fared numerically but not statistically better with alteplase (5.5% vs 6.3%; P = 0.106).
Clinical Implications
Tenecteplase appears to be comparable to alteplase in 30-day mortality. Its primary advantage is the ease of administration. It also appears to have a slightly lower incidence of major bleeding and need for transfusion. The ease of administration may shorten the time between the onset of AMI symptoms and thrombolysis. A course of treatment for tenecteplase is about $2000, which is comparable to the cost of alteplase. v
References
1. TNKase Product Labeling. Genentech Inc. May 2000.
2. ASSENT-2 Investigators. Lancet 1999;354:716-722.
3. Keyt BA, et al. Proc Natl Acad Sci USA 1994;91: 3670-3674.
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