ELAXIM

Tenecteplase is a tissue plasminogen activator (tPA) developed from modifications of natural human tPA complementary DNA (cDNA).

It is a 527 amino acid with a substitution of threonine with asparagine and substitution of asparagine with glutamine within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296-299 in the protease domain.

Tenecteplase is indicated for the treatment of acute ischemic stroke (AIS) in adult patients and to reduce the risk of death in adult patients following acute ST-elevated myocardial infarction (STEMI). 6,

Tenecteplase is a fibrin-specific tissue-plasminogen activator.

It binds to fibrin rich clots and cleaves the Arg/Val bond in plasminogen to form plasmin.

Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.

This helps eliminate blood clots or arterial blockages that cause myocardial infarction.

hours (mammalian reticulocytes, in vitro)

20 hours (yeast, in vivo) 10 hours (Escherichia coli, in vivo).

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TNKase is contraindicated in patients with

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 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.

Initiate treatment as soon as possible after the onset of STEMI symptoms.

TNKase is for intravenous administration only, administered as a single bolus over 5 seconds.

Individualize dosage based on patient's weight. 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.

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 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.

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.

The reconstituted preparation results in a colorless to pale yellow transparent solution.

Determine the appropriate dose of

TNKase 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.

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.

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.

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 (tenecteplase) for injection is supplied as a sterile, white to pale yellow lyophilized powder in a 50 mg single-dose vial under partial vacuum.

Each 50 mg single-dose vial of TNKase is packaged with one 10 mL single-dose vial of Sterile Water for Injection, USP for reconstitution, and the B-D ® 10 mL syringe with TwinPak™ Dual Cannula Device: NDC 50242-120-47. 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.

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.

Risk Summary There are risks to the mother and fetus from acute ST elevation myocardial infarction, which is a medical emergency in pregnancy and can be fatal if left untreated.

Published data consisting of a small number of case reports involving the use of related thrombolytic agents in pregnant women have not identified an increased risk of major birth defects.

There are no data on the use of tenecteplase during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

TNKase does not elicit maternal and direct embryo toxicity in rabbits following a single IV administration.

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 STEMI.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Maternal and/or Embryo/Fetal Risk Myocardial infarction is a medical emergency which can be fatal if left untreated.

Life-sustaining therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of tenecteplase on the fetus.

The safety and effectiveness of

TNKase in pediatric patients have not been established.

In the

ASSENT-2 study, 41% (3500/8458) of patients who were treated with TNKase were aged 65 years or older.

In this population, rates of 30-day mortality, stroke, intracranial hemorrhage and major bleeds requiring blood transfusion or leading to hemodynamic complications were higher than in those aged less than 65 years.