1000 variants of rt-PA were evaluated, resulting in the identification of key structure-function relationships.1 The three targeted alterations which differentiate TNKase from the rt-PA molecule contribute to the following pharmacological improvements:
||Increased Fibrin Specificity
|TNKase has 8-10 times the fibrin selectivity in vitro of Activase® (alteplase)1 (the clinical significance of increased fibrin specificity has not been established)2
||Greater Resistance to Plasminogen Activator Inhibitor-1 (PAI-1)2
|TNKase is more resistant to PAI-1 in vitro, relative to Activase. PAI-1 is a natural fibrinolysis inhibitor that can disrupt plasminogen activation
|The initial half-life of TNKase is approximately 3 to 6 times that of Activase in vivo, allowing it to be delivered in one single bolus over 5 seconds
The clinical significance of increased fibrin specificity, greater resistance to PAI-1, and long plasma half-life have not been established.
TNKase® (Tenecteplase) is indicated for
use in the reduction of mortality associated with acute myocardial infarction
(AMI). Treatment should be initiated as soon as possible after the onset of AMI
Important Safety Information
TNKase therapy in patients with AMI is contraindicated in
the following situations because of an increased risk of bleeding: active
internal bleeding; history of cerebrovascular accident; intracranial or
intraspinal surgery, or trauma within 2 months; intracranial neoplasm,
arteriovenous malformation, or aneurysm; known bleeding diathesis; and
severe uncontrolled hypertension.
The most common complication encountered during TNKase
therapy is bleeding. Should serious bleeding (not controlled by local
pressure) occur, any concomitant heparin or antiplatelet agents should be
In clinical studies of TNKase, patients were treated with
both aspirin and heparin. Heparin may contribute to the bleeding risks
associated with TNKase. The safety of the use of TNKase with other
antiplatelet agents has not been adequately studied. Intramuscular injections
and nonessential handling of the patient should be avoided for the first few
hours following treatment with TNKase.
The risk of bleeding may be increased in the following
conditions and should be weighed against the anticipated benefits: recent
major surgery, cerebrovascular disease, recent gastrointestinal or
genitourinary bleeding, recent trauma, hypertension, high likelihood of left
heart thrombus, acute pericarditis, subacute bacterial endocarditis,
hemostatic defects, severe hepatic dysfunction, pregnancy, diabetic
hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions, septic
thrombophlebitis or occluded AV cannula at seriously infected site, advanced
age, patients currently receiving oral anticoagulants, recent administration
of GP IIb/IIIa inhibitors, and any other condition in which bleeding
constitutes a significant hazard or would be particularly difficult to manage
because of its location.
Cholesterol embolism has been reported rarely in patients
treated with all types of thrombolytic agents; the true incidence is unknown.
This serious condition, which can be lethal, is also associated with invasive
vascular procedures (e.g., cardiac catheterization, angiography, vascular
surgery) and/or anticoagulant therapy.
Coronary thrombolysis may result in arrhythmias associated
with reperfusion. It is recommended that anti-arrhythmic therapy for
bradycardia and/or ventricular irritability be available when TNKase is
Use with Percutaneous Coronary Intervention (PCI)
In patients with large ST-segment elevation myocardial
infarction, physicians should choose either thrombolysis or PCI as the primary
treatment strategy for reperfusion.
Standard management of myocardial infarction should be
implemented concomitantly with TNKase treatment.
Pregnancy (Category C)
There are no adequate and well-controlled studies in
pregnant women. TNKase should be given to pregnant women only if the potential
benefits justify the potential risk to the fetus.
It is not known if TNKase is excreted in human milk. Because
many drugs are excreted in human milk, caution should be exercised when TNKase
is administered to a nursing woman.
In elderly patients, the benefits of TNKase on mortality
should be carefully weighed against the risk of increased adverse events,
The most frequent adverse reaction associated with TNKase
Should serious bleeding occur, concomitant heparin and
antiplatelet therapy should be discontinued. Death or permanent disability
can occur in patients who experience stroke or serious bleeding episodes.
For TNKase-treated patients in ASSENT-2, the incidence of
intracranial hemorrhage was 0.9% and incidence of any stroke was 1.8%. The
incidence of all strokes, including intracranial bleeding, increases with
Allergic-type reactions (e.g., anaphylaxis, angioedema,
laryngeal edema, rash, and urticaria) have rarely (<1%) been reported in
patients treated with TNKase. Anaphylaxis was reported in <0.1% of patients
treated with TNKase; however, causality was not established.
The following adverse reactions have been reported among
patients receiving TNKase in clinical trials: cardiogenic shock, arrhythmias,
atrioventricular block, pulmonary edema, heart failure, cardiac arrest,
recurrent myocardial ischemia, myocardial reinfarction, myocardial rupture,
cardiac tamponade, pericarditis, pericardial effusion, mitral regurgitation,
thrombosis, embolism, and electromechanical dissociation. These events can be
life-threatening and may lead to death. Nausea and/or vomiting, hypotension,
and fever have also been reported.
Please see full Prescribing Information for additional
Important Safety Information.
Bennett WF, Paoni NF, Keyt BA, et al. High resolution analysis of functional determinants on human tissue-type plasminogen activator. J Biol Chem. 1991;266:5191-5201.|
|2. ||Cannon CP, McCabe CH, Gibson CM, et al. TNK-tissue plasminogen activator in acute myocardial infarction: results of the Thrombolysis Myocardial Infarction (TIMI) 10A dose-ranging trial. Circulation. 1997;95:351-356.|