Metalyse

Metalyse is indicated in Acute phase of myocardial infarction (AMI).

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 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.

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

No formal interaction studies with Metalyse 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 Metalyse therapy.

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; and severe uncontrolled hypertension.

The most frequent adverse reaction associated with Metalyse is bleeding. If serious bleeding occurs, concomitant heparin and antiplatelet therapy should be discontinued. Death or permanent disability can occur in patients who experience stroke or serious bleeding episodes.For Metalyse-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. Non-intracranial major bleeding and the need for blood transfusions were lower in patients treated with Metalyse.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%). The following adverse reactions have been reported among patients receiving Metalyse in clinical trials. These reactions are frequent sequelae of the underlying disease, and the effect of Metalyse 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.

The benefit of treatment must be evaluated against the potential risks in case of myocardial infarction during pregnancy. It is not known if tenecteplase is excreted into breast milk. It is not known if Tenecteplase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when tenecteplase is administered to a nursing woman.

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

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

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