Tenecteplase (Metalize) is prepared by the process of recombinant DNA technology. It is almost similar to alteplase except for minor structural changes. Compared to alteplase, tenecteplase is more specific and has a longer half-life.

• ST-elevation myocardial infarction:

  • it is used in the management of ST-elevation myocardial infarction (STEMI) for the lysis of thrombi in the coronary vasculature to restore perfusion and reduce mortality.

• Recommended criteria for treatment of STEMI :

  • it is used in Ischemic symptoms within 12 hours of treatment or evidence of ongoing ischemia 12 to 24 hours after symptom onset with a large area of myocardium at risk or hemodynamic instability.

• Off Label Usage of Tenecteplase in Adults:

  • Pulmonary embolism, acute (hemodynamically unstable/massive);

  • Pulmonary embolism, acute (hemodynamically stable/submassive);

  • Pulmonary embolism associated with cardiac arrest

Tenecteplase dose in Adults

Tenecteplase dose in the treatment of Pulmonary embolism, acute (hemodynamically unstable/massive) (off-label):

• Infuse the dose intravenously as a single bolus over 5 to 10 seconds

  • <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

Tenecteplase dose in the treatment of acute Pulmonary embolism, (hemodynamically stable/submassive) (off-label):

• Not advised for most patients with acute PE without hypotension
• It should be used only in selected patients showing clinical signs of deterioration despite maintaining a systolic BP >90 mm Hg where benefits outweigh risks
• Administer the dose intravenously as a single bolus over 5 to 10 seconds :

  • <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

Tenecteplase dose in the treatment of Pulmonary embolism associated with cardiac arrest (off-label):

• Administer intravenously as a single bolus over 5 seconds :

  • <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

Tenecteplase dose in the treatment of STEMI:

• The advised total dose should not exceed 50 mg and is based on weight.
• Infuse as a single bolus over 5 seconds:

  • <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

Use in Children:

Tenecteplase is not recommended for use in children.

Tenecteplase pregnancy Risk Factor: C

• Some animal reproduction studies have shown adverse events.
• Pregnant women may be at greater risk of bleeding.
• Only give this medication to pregnant women if it is worth the risk to the unborn baby.

Tenecteplase use during breastfeeding:

• It is unknown if breast milk contains tenecteplase or not.
• Tenecteplase should be administered to nursing mothers with caution, according to the manufacturer.

Tenecteplase dose in renal disease:

• No dosage adjustment required.

Hemodialysis:

• Dialyzable: Unknown, but unlikely

Tenecteplase dose in Liver disease:

• Mild to moderate impairment:

  • No dosage adjustment is given in the manufacturer's labeling.

• Severe impairment:

  • No dosage adjustment is given in the manufacturer's labeling
  • weigh the risk of bleeding against the benefits with tenecteplase especially in patients with a coagulopathy.

Common Side Effects of Tenecteplase (Metalize):

• Hematologic & oncologic:

  • Hemorrhage
  • Hematoma

Less Common Side Effects of Tenecteplase (Metalize):

• Cardiovascular:

  • Cerebrovascular Accident

• Gastrointestinal:

  • Gastrointestinal Hemorrhage

• Genitourinary:

  • Genitourinary Tract Hemorrhage

• Hematologic & Oncologic:

  • Local Hemorrhage

• Respiratory:

  • Pharyngeal Bleeding
  • Epistaxis

Rare side effects of Tenecteplase (Metalize):

• Cardiovascular:

  • Atrioventricular Block
  • Cardiac Arrhythmia
  • Cardiac Failure
  • Cardiac Tamponade
  • Cardiogenic Shock
  • Embolism
  • Hypotension
  • Ischemic Heart Disease
  • Mitral Valve Insufficiency
  • Myocardial Reinfarction
  • Myocardial Rupture
  • Pericardial Effusion
  • Pericarditis
  • Pulmonary Edema
  • Thrombosis

• Gastrointestinal:

  • Nausea
  • Vomiting

• Miscellaneous:

  • Fever

Contraindications to Tenecteplase (Metalize):

Treatment STEMI:

• Active internal bleeding
• History of cerebrovascular accidents
• Intracranial, intraspinal or trauma surgery (within the last 2 months).
• Intracranial Neoplasm
• Aneurysm or arteriovenous malformation
• bleeding diathesis
• Hypertension that is not controlled and severe
• Within 3 months, Ischemic stroke
• Prior intracranial hemorhage
• active bleeding (excluding menses)
• Suspected aortic dissection
• Significant facial trauma or closed head trauma within three months
• Hypersensitivity to tenecteplase and any part of its formulation

Off-label treatment for pulmonary embolism

• Structural intracranial diseases
• Previous intracranial hemorhage
• Ischemic stroke in 3 months
• active bleeding
• Recent brain and spinal surgery
• Recent head trauma with fractures or brain injury
• bleeding diathesis

Warnings and precautions

• Arrhythmias:
• • Reperfusion arrhythmias can be caused by coronary thrombolysis (eg, sinus bradycardia or accelerated idioventricular rhythm), ventricular premature depolarizations, and ventricular tachycardia.
  • Therapy should include antiarrhythmic therapy.
• Bleeding
  • Internal bleeding can occur (intracranial or gastrointestinal, retroperitoneal and genitourinary) or externally (especially at puncture points).
  • All bleeding areas should be monitored
  • Patients who develop significant bleeding, the infusion of tenecteplase and any other concurrent anticoagulants like heparin and antiplatelets like aspirin should be withheld and the patient should be treated appropriately.
• Cholesterol embolization:
  • Patients treated with thrombolytic drugs have rarely experienced cholesterol embolization.
  • Cholesterol embolization can cause livedo reticularis, "purple-toe" syndrome, hypertension and pancreatitis. It is possible for patients to become fatal.
• Hypersensitivity reactions
  • After administration, hypersensitivity reactions have been observed (eg anaphylaxis and urticaria, laryngeal swelling, rash, and laryngeal effusion).
  • You should be aware of hypersensitivity reactions and monitor closely during infusions as well as for several hours afterwards.
  • If hypersensitivity symptoms are present, you should seek appropriate treatment.
• Events that are thromboembolic:
  • Patients with high risk of left-heart thrombosis (eg patients with mitral or atrial fibrillation) might be more susceptible to thromboembolic events.
• Conditions that increase bleeding risk
  • The risk of bleeding in the following conditions is higher when using thrombolytics. This should be considered along with the benefits of therapy.
• Pulmonary embolism
  • Blood pressure readings higher than 180/110mm Hg
  • Recent bleeding (non intracranial)
  • Recent surgery or an invasive procedure
  • ischemic stroke >3 months previously
  • Anticoagulated (e.g. VKA therapy).
  • Traumatic CPR
  • Pericarditis and pericardial fluid
  • Diabetic retinopathy
  • Age >75
  • Low body weight (60kg)
  • Female
  • Black
• ST-elevation myocardial Infarction
  • History of hypertension that was severe and chronically uncontrolled
  • Significant hypertension upon presentation (systolic blood pressure >180 mm Hg, or diastolic blood pressure >110 mmHg).
  • History of ischemic strokes in the past >3 months
  • Alzheimer's
  • Traumatic or prolonged CPR (>10 mins)
  • Major surgery takes 3 weeks
  • Recent internal bleeding (within 2-4 weeks)
  • noncompressible vascular punctures
  • Active peptic ulcer
  • Oral anticoagulant therapy
  • Lumbar puncture in 10 days

Tenecteplase: Drug Interaction

Monitor:

• CBC
• aPTT
• signs and symptoms of bleeding
• ECG monitoring

How to administer Tenecteplase (Metalize)?

• Tenecteplase is incompatible with dextrose solutions.
• Dextrose-containing lines should be flushed with a saline solution before and after administration.
• Administer over 5 seconds as a single intravenous bolus dose.
• Avoid intramuscular injections and nonessential handling of the patient.

Mechanism of action of Tenecteplase (Metalize):

• It stimulates fibrinolysis by binding fibrin to it and converting plasminogen into plasmin.
• Tenecteplase has a similar structure to alteplase, with 3 exceptions. It is more fibrin-specific, more resistant to the plasminogen activator inhibit -1 (PAI-1), and has a longer duration than alteplase.
• It is made using recombinant DNA technology and a mammalian cell (Chinese Hamster ovary cells).

Distribution:

• V is weight-related and approximates plasma volume

Metabolism:

• Primarily hepatic

Half-life elimination:

• Biphasic:
  • Initial: 20 - 24 minutes;
  • Terminal: 90 - 130 minutes

Excretion:

• Clearance: Plasma: 99 to 119 mL/minute

International Brand Names of Tenecteplase:

• Elaxim
• Metalize
• Metalyse

Tenecteplase Brand Names in Pakistan:

Tenecteplase is not available in Pakistan.