TNKASE

Tenecteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using a mammalian cell line (Chinese Hamster Ovary cells). Tenecteplase is a 527-amino acid glycoprotein developed by introducing the following modifications to the complementary DNA (cDNA) for natural human tPA: a substitution of threonine 103 with asparagine, and a substitution of asparagine 117 with glutamine, both within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain. It has a molecular weight of 58,742 daltons. Biological potency is determined by an in vitro clot lysis assay and is expressed in tenecteplase specific units. The specific activity of tenecteplase has been defined as 200 units/mg. TNKase (tenecteplase) for injection is a sterile, white to pale yellow, lyophilized powder for intravenous bolus administration after reconstitution with Sterile Water for Injection, USP. Each single-dose vial of TNKase nominally contains 50 mg of tenecteplase, arginine (522 mg), phosphoric acid (approximately 160 mg), and polysorbate 20 (4.0 mg). Following reconstitution with the supplied 10 mL single-dose vial of Sterile Water for Injection, USP, the final concentration is 5 mg/mL with a pH of approximately 7.3.

TNKase ® is indicated to reduce the risk of death associated with acute ST elevation myocardial infarction (STEMI). TNKase is a tissue plasminogen activator, indicated to reduce the risk of death associated with acute ST elevation myocardial infarction (STEMI). ( 1 )

Initiate treatment as soon as possible after the onset of STEMI symptoms. ( 2.1 ) TNKase is for intravenous administration only, administered as a single bolus over 5 seconds. Individualize dosage based on patient's weight. ( 2.1 ) 2.1 Recommended Dosage Initiate treatment as soon as possible after the onset of STEMI symptoms. TNKase is for intravenous (IV) administration only, administered as a single bolus over 5 seconds. Individualize dosage based on the patient's weight (see Table 1 ). Table 1: Recommended Dosage Patient Weight (kg) TNKase (mg) Volume TNKase From one vial of TNKase reconstituted with 10 mL Sterile Water for Injection. to be administered (mL) < 60 30 6 ≥ 60 to < 70 35 7 ≥ 70 to < 80 40 8 ≥ 80 to < 90 45 9 ≥ 90 50 10 2.2 Preparation Follow the below steps to prepare TNKase for administration: Remove the shield assembly from the supplied B-D ® 10 mL syringe with TwinPak™ Dual Cannula Device (see Figure 1 ) and aseptically withdraw 10 mL of Sterile Water for Injection, USP, from the supplied diluent vial using the red hub cannula syringe filling device. Only use the supplied Sterile Water for Injection, USP for reconstitution. Note: Do not discard the shield assembly. Aseptically reconstitute the vial with 10 mL Sterile Water for Injection, USP by directing the stream into the lyophilized powder to obtain a final concentration of 5 mg/mL. Slight foaming upon reconstitution is not unusual; any large bubbles will dissipate if the product is allowed to stand undisturbed for several minutes. Gently swirl until contents are completely dissolved. DO NOT SHAKE. The reconstituted preparation results in a colorless to pale yellow transparent solution. Determine the appropriate dose of TNKase [see Dosage and Administration (2.1) ] and withdraw this volume (in milliliters) from the reconstituted vial with the syringe. Discard any unused solution. Stand the shield vertically on a flat surface (with green side down) and passively recap the red hub cannula. Remove the entire shield assembly, including the red hub cannula, by twisting counterclockwise. Note: The shield assembly also contains the clear-ended blunt plastic cannula; retain for split septum intravenous access. Figure 1 Figure 1 2.3 Administration Follow the below steps for administration of TNKase; Inspect the product prior to administration for particulate matter and discoloration. Administer TNKase as reconstituted at 5 mg/mL. Precipitation may occur when TNKase is administered in an intravenous line containing dextrose. Flush dextrose-containing lines with a saline-containing solution prior to and following single bolus administration of TNKase. Administer reconstituted TNKase as a single intravenous bolus over 5 seconds. Because TNKase contains no antibacterial preservatives, reconstitute immediately before use. If the reconstituted TNKase is not used immediately, refrigerate the TNKase vial at 2°C to 8°C (36°F to 46°F) and use within 8 hours. Although the supplied syringe is compatible with a conventional needle, this syringe is designed to be used with needleless intravenous systems. From the information below, follow the instructions applicable to the intravenous system in use. Split septum intravenous system : Remove the green cap. Attach the clear-ended blunt plastic cannula to the syringe. Remove the shield and use the blunt plastic cannula to access the split septum injection port. Because the blunt plastic cannula has two side ports, air or fluid expelled through the cannula will exit in two sideways directions; direct away from face or mucous membranes. Luer-Lok ® system: Connect syringe directly to intravenous port. Conventional needle (not supplied in this kit): Attach a large bore needle, e.g., 18 gauge, to the syringe's universal Luer-Lok ® . Dispose of the syringe, cannula and shield per established procedures. 2.4 Chemical Incompatibilities TNKase is incompatible with dextrose containing solutions. When used together, precipitation may occur. Flush dextrose containing lines with saline-containing solution before using TNKase.

TNKase is contraindicated in patients with [see Warnings and Precautions (5.1) ] : 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 Severe uncontrolled hypertension Active internal bleeding ( 4 ) History of cerebrovascular accident ( 4 ) Intracranial or intraspinal surgery or trauma within 2 months ( 4 ) Intracranial neoplasm, arteriovenous malformation, or aneurysm ( 4 ) Known bleeding diathesis ( 4 ) Severe uncontrolled hypertension ( 4 )

The following adverse reactions are discussed in other sections of the label: Bleeding [see Contraindications (4) , Warnings and Precautions (5.1) ] Hypersensitivity [see Warnings and Precautions (5.6) ] The most common adverse reactions are bleeding and hypersensitivity. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Roche at 1-800-526-6367 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Immunogenicity Four of 625 (0.64%) patients tested for antibody formation to TNKase had a positive antibody titer at 30 days in studies with TNKase. The observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to TNKase with the incidence of antibodies to other products may be misleading.

During TNKase therapy, results of coagulation tests and/or measures of fibrinolytic activity may be unreliable unless specific precautions are taken to prevent in vitro artifacts. ( 7.1 ) 7.1 Drug/Laboratory Test Interactions During TNKase therapy, results of coagulation tests and/or measures of fibrinolytic activity may be unreliable unless specific precautions are taken to prevent in vitro artifacts. Tenecteplase is an enzyme that, when present in blood in pharmacologic concentrations, remains active under in vitro conditions. This can lead to degradation of fibrinogen in blood samples removed for analysis.

16.2 Stability and Storage Store lyophilized TNKase at room temperature up to 30°C (86°F) or refrigerated at 2°C to 8°C (36°F to 46°F). Do not use beyond the expiration date stamped on the vial.