Tenecteplase is indicated for use in the acute phase of myocardial infarction (AMI).

Tenecteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established 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. Tenecteplase is a sterile, white to off-white, lyophilized powder for single intravenous (IV) bolus administration after reconstitution with Sterile Water for Injection (SWFI), USP. Each vial of tenecteplase nominally contains 52.5 mg tenecteplase, 0.55 g L-arginine, 0.17 g phosphoric acid, and 4.3 mg polysorbate 20, which includes a 5% overfill. Each vial will deliver 50 mg of tenecteplase.

Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA. Tenecteplase binds to fibrin-rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then 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.

Tenecteplase is intended for intravenous use only. The total recommended dose should not exceed 50 mg and is determined based on the patient’s body weight. A single bolus dose should be given over 5 seconds. Treatment should be started as soon as possible after the onset of acute myocardial infarction (AMI) symptoms.

Patient Weight:

• <60 kg: 30 mg
• ≥60 to <70 kg: 35 mg
• ≥70 to <80 kg: 40 mg
• ≥80 to <90 kg: 45 mg
• ≥90 kg: 50 mg

Readministration of plasminogen activators, including Tenecteplase, in patients previously treated with such agents has not been well studied. In clinical evaluation, a small number of patients developed antibodies to Tenecteplase within 30 days. The detection of these antibodies depends on assay sensitivity, sample handling, concurrent medications, and underlying conditions. Therefore, comparisons with other agents may not be reliable. Although sustained antibody formation has not been confirmed, repeat use should be approached with caution.

No formal interaction studies with tenecteplase and medicinal products commonly administered in patients with AMI have been performed. Medicinal products that affect coagulation or those that alter platelet function may increase the risk of bleeding prior to, during or after tenecteplase therapy.

Tenecteplase is contraindicated in patients with active internal bleeding, a history of cerebrovascular accident, recent (within 2 months) intracranial or intraspinal surgery or trauma, intracranial neoplasm, arteriovenous malformation or aneurysm, known bleeding disorders, or severe uncontrolled hypertension.

The most common adverse reaction associated with Tenecteplase is bleeding. In cases of serious bleeding, concomitant heparin and antiplatelet therapy should be discontinued. Stroke or severe bleeding events may result in death or permanent disability. In the ASSENT-2 trial, intracranial hemorrhage occurred in 0.9% of patients, and the overall stroke rate was 1.8%, with risk increasing with age. Major non-intracranial bleeding and the need for blood transfusion were lower compared to other treatments. Major bleeding (≥1%) included hematoma (1.7%) and gastrointestinal bleeding (1%). Less common major bleeding (<1%) involved the urinary tract, puncture sites (including cardiac catheterization sites), retroperitoneal area, respiratory tract, and unspecified sites. Minor bleeding (≥1%) included hematoma (12.3%), urinary tract bleeding (3.7%), puncture site bleeding (3.6%), pharyngeal bleeding (3.1%), gastrointestinal bleeding (1.9%), epistaxis (1.5%), and unspecified bleeding (1.3%).

Other adverse reactions observed in clinical trials include cardiogenic shock, arrhythmias, atrioventricular block, pulmonary edema, heart failure, cardiac arrest, recurrent myocardial ischemia, reinfarction, myocardial rupture, cardiac tamponade, pericarditis, pericardial effusion, mitral regurgitation, thrombosis, embolism, and electromechanical dissociation. These conditions may be life-threatening and can result in death. Additional reported effects include nausea, vomiting, hypotension, and fever.

In cases of myocardial infarction during pregnancy, the potential benefits of treatment should be carefully weighed against the possible risks. It is not known whether Tenecteplase is excreted in human breast milk. As many drugs are known to pass into breast milk, caution should be exercised when administering Tenecteplase to a breastfeeding woman.

General: Standard management of myocardial infarction should be implemented concomitantly with tenecteplase 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 noncompressible sites. In the event of serious bleeding, heparin and antiplatelet agents should be discontinued immediately. Heparin effects can be reversed by protamine.

Hypersensitivity: Hypersensitivity, including urticarial/anaphylactic reactions, have been reported after administration of tenecteplase (e.g., anaphylaxis, angioedema, laryngeal edema, rash, and urticaria). Monitor patients treated with tenecteplase during and for several hours after infusion. If symptoms of hypersensitivity occur, appropriate therapy should be initiated.

Pediatric Use: The safety and effectiveness of tenecteplase in pediatric patients have not been established.

Geriatric Use: Of the patients in ASSENT-2 who received tenecteplase, 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 tenecteplase on mortality should be carefully weighed against the risk of increased adverse events, including bleeding.

In the event of overdose, there may be an increased risk of bleeding. In case of severe prolonged bleeding, substitution therapy (plasma, platelets) may be considered.

Fibrinolytics (Thrombolytics)

Store lyophilized tenecteplase at a temperature not exceeding 30°C or under refrigeration at 2-8°C. Keep out of reach of children.