Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 17 March 2018

Indication(s)

INDICATIONS AND USAGE 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 symptoms (see CLINICAL STUDIES).

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Advisory information

contraindications
CONTRAINDICATIONS TNKase therapy in patients with acute myocardial infarction is contraindicated in the following situations because of an increased risk of bleeding (see WARNINGS): 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
Special warnings and precautions
PRECAUTIONS General Standard management of myocardial infarction should be implemented concomitantly with TNKase treatment. Arterial and venous punctures should be minimized. Noncompressible arterial puncture must be avoided and internal jugular and subclavian venous punctures should be avoided to minimize bleeding from the noncompressible sites. In the event of serious bleeding, heparin and antiplatelet agents should be discontinued immediately. Heparin effects can be reversed by protamine. Readministration Readministration of plasminogen activators, including TNKase, to patients who have received prior plasminogen activator therapy has not been systematically studied. Three of 487 patients tested for antibody formation to TNKase had a positive antibody titer at 30 days. The data reflect the percentage of patients whose test results were considered positive for antibodies to TNKase in a radioimmunoprecipitation assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally, 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. Although sustained antibody formation in patients receiving one dose of TNKase has not been documented, readministration should be undertaken with caution. Hypersensitivity Hypersensitivity, including urticarial / anaphylactic reactions, have been reported after administration of TNKase (e.g., anaphylaxis, angioedema, laryngeal edema, rash, and urticaria). Monitor patients treated with TNKase during and for several hours after infusion. If symptoms of hypersensitivity occur, appropriate therapy should be initiated. Drug Interactions Formal interaction studies of TNKase with other drugs have not been performed. Patients studied in clinical trials of TNKase were routinely treated with heparin and aspirin. Anticoagulants (such as heparin and vitamin K antagonists) and drugs that alter platelet function (such as acetylsalicylic acid, dipyridamole, and GP IIb/IIIa inhibitors) may increase the risk of bleeding if administered prior to, during, or after TNKase therapy. 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. Carcinogenesis, Mutagenesis, Impairment of Fertility Studies in animals have not been performed to evaluate the carcinogenic potential, mutagenicity, or the effect on fertility. Pregnancy TNKase has been shown to elicit maternal and embryo toxicity in rabbits given multiple IV administrations. In rabbits administered 0.5, 1.5, and 5.0 mg/kg/day during organogenesis, vaginal hemorrhage resulted in maternal deaths. Subsequent embryonic deaths were secondary to maternal hemorrhage and no fetal anomalies were observed. TNKase does not elicit maternal and embryo toxicity in rabbits following a single IV administration. Thus, in developmental toxicity studies conducted in rabbits, the no observable effect level (NOEL) of a single IV administration of TNKase on maternal or developmental toxicity (5 mg/kg) was approximately 7 times human exposure (based on AUC) at the dose for AMI. 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. Nursing Mothers 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. Pediatric Use The safety and effectiveness of TNKase in pediatric patients have not been established. Geriatric Use Of the patients in ASSENT-2 who received TNKase, 4,958 (59%) were under the age of 65; 2,256 (27%) were between the ages of 65 and 74; and 1,244 (15%) were 75 and over. The 30-day mortality rates by age were 2.5% in patients under the age of 65, 8.5% in patients between the ages of 65 and 74, and 16.2% in patients age 75 and over. The ICH rates were 0.4% in patients under the age of 65, 1.6% in patients between the ages of 65 and 74, and 1.7% in patients age 75 and over. The rates of any stroke were 1.0% in patients under the age of 65, 2.9% in patients between the ages of 65 and 74, and 3.0% in patients age 75 and over. Major bleeding rates, defined as bleeding requiring blood transfusion or leading to hemodynamic compromise, were 3.1% in patients under the age of 65, 6.4% in patients between the ages of 65 and 74, and 7.7% in patients age 75 and over. In elderly patients, the benefits of TNKase on mortality should be carefully weighed against the risk of increased adverse events, including bleeding.
Adverse reactions
ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in Section PRECAUTIONS of the label: Hypersensitivity Bleeding The most frequent adverse reaction associated with TNKase is bleeding (see WARNINGS). 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 any stroke was 1.8%. The incidence of all strokes, including intracranial bleeding, increases with increasing age (see PRECAUTIONS: Geriatric Use). In the ASSENT-2 study, the following bleeding events were reported (see Table 3). Table 3 ASSENT-2 Non-ICH Bleeding Events TNKase (n = 8461) Accelerated Activase (n = 8488) Relative Risk for TNKase/Activase (95% CI) Major bleedingMajor bleeding is defined as bleeding requiring blood transfusion or leading to hemodynamic compromise. 4.7% 5.9% 0.78 (0.69, 0.89) Minor bleeding 21.8% 23.0% 0.94 (0.89, 1.00) Units of transfused blood Any 4.3% 5.5% 0.77 (0.67, 0.89) 1–2 2.6% 3.2% >2 1.7% 2.2% Non-intracranial major bleeding and the need for blood transfusions were lower in patients treated with TNKase. Types of major bleeding reported in 1% or more of the patients were hematoma (1.7%) and gastrointestinal tract (1%). Types of major bleeding reported in less than 1% of the patients were urinary tract, puncture site (including cardiac catheterization site), retroperitoneal, respiratory tract, and unspecified. Types of minor bleeding reported in 1% or more of the patients were hematoma (12.3%), urinary tract (3.7%), puncture site (including cardiac catheterization site) (3.6%), pharyngeal (3.1%), gastrointestinal tract (1.9%), epistaxis (1.5%), and unspecified (1.3%). Other Adverse Reactions The following adverse reactions have been reported among patients receiving TNKase in clinical trials. These reactions are frequent sequelae of the underlying disease, and the effect of TNKase on the incidence of these events is unknown. These events include 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.

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION Dosage TNKase® (Tenecteplase) is for intravenous administration only. The recommended total dose should not exceed 50 mg and is based upon patient weight. A single bolus dose should be administered over 5 seconds based on patient weight. Treatment should be initiated as soon as possible after the onset of AMI symptoms (see CLINICAL STUDIES). Dose Information Table Patient Weight (kg) TNKase (mg) Volume TNKaseFrom one vial of TNKase reconstituted with 10 mL SWFI. 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 The safety and efficacy of TNKase have only been investigated with concomitant administration of heparin and aspirin as described in CLINICAL STUDIES. THE ® 10 mL SYRINGE WITH TWINPAK™ DUAL CANNULA DEVICE B-D DUAL CANNULA DEVICE Reconstitution NOTE: Read all instructions completely before beginning reconstitution and administration. Remove the shield assembly from the supplied B-D® 10 mL syringe with TwinPak™ Dual Cannula Device (see figure) and aseptically withdraw 10 mL of Sterile Water for Injection (SWFI), USP, from the supplied diluent vial using the red hub cannula syringe filling device. Do not use Bacteriostatic Water for Injection, USP. Note: Do not discard the shield assembly. Inject the entire contents of the syringe (10 mL) into the TNKase vial directing the diluent stream into the powder. 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 containing TNKase at 5 mg/mL at a pH of approximately 7.3. The osmolality of this solution is approximately 290 mOsm/kg. Determine the appropriate dose of TNKase (see Dose Information Table) and withdraw this volume (in milliliters) from the reconstituted vial with the syringe. Any unused solution should be discarded. Once the appropriate dose of TNKase is drawn into the syringe, 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 IV access. Administration 1.The product should be visually inspected prior to administration for particulate matter and discoloration. TNKase may be administered as reconstituted at 5 mg/mL. 2.Precipitation may occur when TNKase is administered in an IV line containing dextrose. Dextrose-containing lines should be flushed with a saline-containing solution prior to and following single bolus administration of TNKase. 3.Reconstituted TNKase should be administered as a single IV bolus over 5 seconds. 4.Because TNKase contains no antibacterial preservatives, it should be reconstituted immediately before use. If the reconstituted TNKase is not used immediately, refrigerate the TNKase vial at 2–8°C (36–46°F) and use within 8 hours. 5.Although the supplied syringe is compatible with a conventional needle, this syringe is designed to be used with needleless IV systems. From the information below, follow the instructions applicable to the IV system in use. Split septum IV 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 IV port. Conventional needle (not supplied in this kit): Attach a large bore needle, e.g., 18 gauge, to the syringe's universal Luer‑Lok®. 6.Dispose of the syringe, cannula and shield per established procedures.
Pregnancy and lactation
Nursing Mothers 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.

Interactions

Drug Interactions Formal interaction studies of TNKase with other drugs have not been performed. Patients studied in clinical trials of TNKase were routinely treated with heparin and aspirin. Anticoagulants (such as heparin and vitamin K antagonists) and drugs that alter platelet function (such as acetylsalicylic acid, dipyridamole, and GP IIb/IIIa inhibitors) may increase the risk of bleeding if administered prior to, during, or after TNKase therapy.

More information

Category Value
Authorisation number BLA103909
Orphan designation No
Product NDC 50242-120
Date Last Revised 08-03-2018
Type HUMAN PRESCRIPTION DRUG
RXCUI 313212
Marketing authorisation holder Genentech, Inc.