Nectelisa^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Generium, JSC (Russia)

ATC Code

B01AD11 (Tenecteplase)

Active Substance

Tenecteplase (Rec.INN registered by WHO)

Dosage Form

Nectelisa®

Lyophilisate for preparation of solution for intravenous administration 50 mg

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for intravenous administration

50 mg – vials – cardboard packs /in a kit with solvent (vials) 10 ml, adapter -1 pc., syringe – 1 pc., needle – 2 pcs. and alcohol wipes – 3 pcs./ – Prescription only
50 mg – vials – cardboard packs /in a kit with solvent (vials) 10 ml, aspiration cannula -1 pc., syringe – 1 pc., needle – 2 pcs. and alcohol wipes – 3 pcs./ – Prescription only
50 mg – vials – cardboard packs /in a kit with solvent (syringes) 10 ml, adapter -1 pc., needle – 1 pc. and alcohol wipes – 2 pcs./ – Prescription only
50 mg – vials – cardboard packs /in a kit with solvent (syringes) 10 ml, aspiration cannula -1 pc., needle – 1 pc. and alcohol wipes – 2 pcs./ – Prescription only

Clinical-Pharmacological Group

Fibrinolytic – recombinant, genetically modified plasminogen activator

Pharmacotherapeutic Group

Antithrombotic agents; enzymes

Pharmacological Action

Fibrinolytic agent, recombinant plasminogen activator, genetically modified.

Tenecteplase is a recombinant fibrin-specific plasminogen activator, a derivative of natural tissue plasminogen activator modified in three regions.

Tenecteplase binds to the fibrin component of a thrombus and selectively catalyzes the conversion of thrombus-bound plasminogen to plasmin, which destroys the fibrin framework of the thrombus. Compared to natural tissue plasminogen activator, Tenecteplase has a higher affinity for fibrin and is resistant to the inactivating action of the endogenous plasminogen activator inhibitor I.

After tenecteplase administration, a dose-dependent consumption of α₂-antiplasmin (plasmin inhibitor in the liquid phase) is observed, followed by an increase in systemic plasmin concentration, which corresponds to the expected plasminogen activation effect. In comparative studies in patients receiving maximum doses of tenecteplase (10,000 IU, equivalent to 50 mg), fibrinogen concentration decreased by less than 15%, and plasminogen concentration by less than 25%, whereas alteplase use led to a decrease in fibrinogen and plasminogen concentrations of approximately 50%.

Angiographic data show that a single intravenous administration of tenecteplase promotes recanalization of the artery, the thrombosis of which led to acute myocardial infarction. This effect is dose-dependent.

Pharmacokinetics

Tenecteplase is eliminated from the bloodstream by binding to receptors in the liver and degradation to form small peptides.

After a single injection of tenecteplase in patients with acute myocardial infarction, a biphasic elimination of the tenecteplase antigen from blood plasma was noted. In the therapeutic dose range, no dependence of tenecteplase elimination on the administered dose is observed.

The initial T_1/2 is 24±5.5 min (mean ± standard deviation), which is 5 times greater than the T_1/2 of natural tissue plasminogen activator. The terminal T_1/2 is 129±87 min; plasma clearance is 119±49 ml/min.

With increased body weight, a moderate increase in plasma clearance is observed; with increasing age, a decrease in this indicator is noted. In women, plasma clearance rates are usually lower than in men, which may be explained by lower body weight in women.

Indications

Thrombolytic therapy of acute myocardial infarction.

ICD codes

Dosage Regimen

Administer as a single intravenous bolus injection over 5-10 seconds.

Initiate therapy as early as possible following the onset of acute myocardial infarction symptoms.

Calculate the dose strictly based on the patient’s body weight.

Use the following dosing table for precise calculation: For body weight less than 60 kg, administer 6000 IU (30 mg); for 60 to 69 kg, administer 7000 IU (35 mg); for 70 to 79 kg, administer 8000 IU (40 mg); for 80 to 89 kg, administer 9000 IU (45 mg); for 90 kg or more, administer 10000 IU (50 mg).

Do not exceed the maximum dose of 10000 IU (50 mg) under any circumstances.

Reconstitute the lyophilisate immediately before use with the provided solvent.

Do not administer as an infusion.

Carefully inspect the solution visually for particulate matter and discoloration prior to administration.

Adverse Reactions

Most frequently: bleeding. Bleeding at any site/body cavity can lead to a life-threatening situation, disability, or death.

From the immune system: anaphylactoid reactions, including rash, urticaria, bronchospasm, laryngeal edema.

From the nervous system: intracranial hemorrhage (cerebral hemorrhage, brain hematoma, hemorrhagic stroke, hemorrhagic transformation of stroke, intracranial hematoma, subarachnoid hemorrhage). The following neurological syndromes may be associated with intracranial hemorrhages: drowsiness, aphasia, hemiparesis, convulsions.

From the organ of vision: intraocular hemorrhage.

From the heart: reperfusion arrhythmias (asystole, idioventricular tachyarrhythmia, arrhythmia, extrasystole, atrial fibrillation, AV-block from first degree to complete block, bradycardia, tachycardia, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia). Reperfusion arrhythmias can lead to cardiac arrest, be life-threatening and require the use of conventional antiarrhythmic therapy; pericardial bleeding.

Vascular disorders: bleeding, embolisms.

From the respiratory system: epistaxis, pulmonary hemorrhage.

From the digestive system: gastrointestinal bleeding (gastric bleeding, bleeding from gastric ulcer, rectal bleeding, hematemesis, melena, oral bleeding), nausea, vomiting, bleeding into the retroperitoneal space (retroperitoneal hematoma).

From the skin and subcutaneous tissues: ecchymoses.

From the genitourinary system: urogenital bleeding (hematuria, bleeding from the urinary tract).

Local reactions: external bleeding, usually from puncture sites or from damaged blood vessels.

General reactions associated with administration: fat embolism, which can lead to corresponding consequences from the affected internal organs.

Surgical and therapeutic procedures: need for blood transfusion.

Other: decreased blood pressure, increased body temperature.

Contraindications

Diseases accompanied by significant bleeding within the last 6 months, hemorrhagic diathesis; simultaneous use of oral anticoagulants (INR>1.3); history of CNS diseases (neoplasms, aneurysm, surgical intervention on the brain and spinal cord); severe uncontrolled arterial hypertension; major surgical interventions, biopsy of a parenchymal organ, or significant trauma within the last 2 months (including trauma combined with current acute myocardial infarction), recently suffered craniocerebral trauma; prolonged or traumatic cardiopulmonary resuscitation (>2 min) within the last 2 weeks; severe liver dysfunction, including liver failure, cirrhosis, portal hypertension (including with esophageal varices) and active hepatitis; peptic ulcer of the stomach or duodenum in the acute phase; arterial aneurysm or presence of arterial/venous vascular malformation; neoplasm with an increased risk of bleeding; acute pericarditis and/or subacute bacterial endocarditis; acute pancreatitis; history of hemorrhagic stroke or stroke of unknown etiology; ischemic stroke or transient ischemic attack within the last 6 months; hypersensitivity to tenecteplase.

Use in Pregnancy and Lactation

There is no experience with the use of tenecteplase during pregnancy. There are no data on the excretion of tenecteplase into breast milk.

If it is necessary to use it in case of acute myocardial infarction during pregnancy or lactation (breastfeeding), the expected benefit for the mother should be weighed against the potential risk to the fetus or child.

Special Precautions

Use tenecteplase with caution and after careful assessment of the expected benefit of treatment and the possible risk of bleeding in case of systolic BP >160 mm Hg; recently experienced gastrointestinal or genitourinary bleeding (within the last 10 days); recently performed intramuscular injection (within the last 2 days); in elderly patients (over 75 years); with low body weight (< 60 kg); cerebrovascular diseases.

If percutaneous coronary intervention (PCI) is planned according to current guidelines (treatment standards), tenecteplase should not be pre-administered at the full dose concomitantly with a single bolus of up to 4000 IU of unfractionated heparin, administered within 60-180 minutes before primary PCI in patients with extensive myocardial infarction.

The most frequent complication associated with the use of tenecteplase is bleeding. Simultaneous use of heparin may contribute to bleeding occurrence. After fibrin dissolution as a result of tenecteplase use, bleeding may occur at sites of recent punctures and injections. Therefore, thrombolytic treatment requires careful monitoring of areas of potential bleeding (including the catheter insertion site, arterial and venous puncture sites, incisions, and injections). The use of rigid catheters, intramuscular injections, and unnecessary manipulations should be avoided during tenecteplase treatment.

In case of serious bleeding, especially intracranial hemorrhage, concomitant heparin administration should be stopped immediately. Protamine sulfate may be prescribed if heparin was administered within 4 hours before the bleeding occurred. When conservative therapy is ineffective, transfusion medications may be indicated. Transfusion of cryoprecipitate, fresh frozen plasma, and platelets may be prescribed according to clinical and laboratory parameters determined repeatedly after each administration. Infusion of cryoprecipitate is desirable until a fibrinogen concentration of about 1 g/l is achieved. Antifibrinolytic agents may also be used.

Coronary thrombolysis may be accompanied by the occurrence of reperfusion-associated arrhythmia. Reperfusion arrhythmias can lead to cardiac arrest, be life-threatening, and require the use of conventional antiarrhythmic therapy.

Concomitant use of glycoprotein IIb/IIIa antagonists increases the risk of bleeding.

The use of tenecteplase may be accompanied by an increased risk of thromboembolic complications in patients with left heart thrombosis, including mitral stenosis or atrial fibrillation.

In case of manifestation of an anaphylactoid reaction, the injection should be discontinued.

Drug Interactions

Medicinal products affecting coagulation, as well as drugs affecting platelet function, when used before, simultaneously with, or after tenecteplase administration, can increase the risk of bleeding.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.