TNKase® (Tenecteplase)
TNKase® (Tenecteplase) is a single-bolus thrombolytic, or clot-busting agent, approved by the U.S. Food and Drug Administration for use in mortality reduction associated with acute myocardial infarction (AMI). Treatment should be initiated as soon as possible after the onset of AMI symptoms. It is the first thrombolytic to date that can be administered over five seconds and in one dose, which is selected based on the weight of the patient.
- TNKase works by stimulating the body's own clot-dissolving mechanism by activating plasminogen, a naturally occurring substance secreted by endothelial cells in response to injury to the artery walls that contributes to clot formation. When TNKase activates plasminogen, it converts into plasmin, which breaks down the fibrin mesh that binds the clot together. The clot is then dissolved, restoring blood flow to the heart.
The pivotal phase 3 trial, ASSENT 2 (ASsessment of the Safety and Efficacy of a New Thrombolytic agent), which the FDA approval of TNKase primarily is based on, compared TNKase with t-PA or Activase® (Alteplase, recombinant), the most widely-used thrombolytic during the past decade:
- ASSENT 2 yielded the following mortality rates: TNKase, 6.2 percent (n=8,461); Activase, 6.2 percent (n=8,488). There were similar rates for intracranial hemorrhage (Activase, 0.9 percent; TNKase, 0.9 percent) and stroke (Activase, 1.7 percent; TNKase, 1.8 percent).
- Fewer non-intracranial major bleeding complications were observed in patients treated with TNKase as compared to the Activase group, 4.7% vs. 5.9%. This resulted in a reduced need for blood transfusions in the TNKase group (4.3% vs. 5.5%).
All thrombolytic agents increase the risk of bleeding, including intracranial bleeding, and should be used only in eligible patients. In addition, thrombolytic therapy increases the risk of stroke, including hemorrhagic stroke in elderly patients.
TNKase is a bioengineered variant of Activase® (Alteplase, recombinant), which is a recombinant DNA-derived version of naturally occurring tissue plasminogen activator (t-PA). It is constructed with amino acid substitutions at three sites (the letters T, N and K represent the three regions changed from the natural t-PA protein). Together, these substitutions have led to:
- A prolonged half-life that enables single-bolus dosing.
- An enhanced specificity for fibrin, a key component of intracoronary clots (14-fold greater than wild-type t-PA), which results in less disturbance of the body's coagulation, or natural clotting, system.
- The clinical significance of fibrin specificity for safety (e.g. bleeding) or efficacy has not been established.
In addition to its clinical features, TNKase will be provided to the medical community as part of a kit, which will include a needleless injection system, the first thrombolytic to be packaged with this device. This system is designed to comply with new OSHA (Occupational Safety and Health Administration) directives to protect health care workers.
Important Safety Information TNKase therapy should not be used in the following conditions due to an increased risk of bleeding: active internal bleeding, history of stroke, brain or spinal surgery or a serious head injury within 2 months, brain tumor, an abnormal connection between veins and arteries, or abnormal bulge in the wall of an artery, problems with blood clotting, and severe uncontrolled high blood pressure.
The most common side effect with TNKase therapy is bleeding. It can be internal bleeding, bleeding in the brain, bleeding from the digestive system, the urinary system, or the reproductive system, or the lungs. Bleeding can also happen from parts of the body where needles have been injected or parts of the body that have had recent surgery. Blood thinners may increase the risk of bleeding if taken before, during, or after TNKase therapy. Patients should inform their doctor of all prescription and over-the-counter drugs they are currently taking.
A plug of cholesterol that blocks an artery (cholesterol embolism) has been reported rarely in patients treated with all types of clot dissolving agents. This is a serious condition which can be lethal, and is also associated with invasive medical procedures involving the arteries and veins.
Irregular heart beats can also occur with TNKase therapy. In serious heart attack patients, doctors should choose either drug therapy that dissolves blood clots or a mechanical means to remove the clot as the main treatment strategy.