An Advanced Lytic by Design

Genentech's goal in developing TNKase was to create a thrombolytic with refined clinical properties relative to wild-type recombinant tissue plasminogen activator (rt-PA). TNKase incorporates three targeted alterations, each of which contributes to the pharmacological improvements that are seen in TNKase relative to rt-PA. The process of designing TNKase began with a systematic effort to map critical features of the rt-PA molecule responsible for its clinical

properties.¹ Using site-directed mutagenesis, researchers evaluated over 1,000 variants of rt-PA, allowing them to identify key structure-function relationships.² Three targeted substitutions differentiate TNKase from the rt-PA molecule and contribute to the following pharmacological improvements:

Increased Fibrin Specificity1

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TNKase has 14-fold greater fibrin selectivity in vitro than Activase® (the clinical significance of increased fibrin specificity has not been established)

Greater Resistance to Plasminogen Activator Inhibitor-1 (PAI-1)1

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TNKase is 80-fold more resistant to PAI-1 in vitro relative to Activase. PAI-1 is a natural inhibitor to fibrinolysis that can disrupt plasminogen activation

Long Plasma Half-Life2

	•	The half-life of TNKase is 5 to 7 times that of Activase in vivo, allowing it to be delivered in one single bolus over 5 seconds
	•	With the exception of TNKase, other lytic agents must be administered either as infusions or as multiple injections

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 discontinued immediately.

In certain conditions (eg, recent major surgery, cerebrovascular disease, hypertension) the risk of TNKase therapy may be increased and should be weighed against the anticipated benefits. [See WARNINGS in full prescribing information].

Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown.

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 administered.

Please see full Prescribing Information for additional important safety information.