Usage
Tenecteplase is prescribed for the reduction of mortality associated with acute myocardial infarction (AMI), particularly ST-elevation myocardial infarction (STEMI). It is also used in some instances, though off-label, for acute ischemic stroke and acute massive pulmonary embolism. It is classified as a thrombolytic agent. Tenecteplase works by activating plasminogen, which subsequently converts to plasmin. Plasmin is an enzyme that breaks down fibrin, the primary component of blood clots. By breaking down fibrin, tenecteplase helps to restore blood flow in blocked arteries.
Alternate Names
Tenecteplase is also known as TNK-tPA. Brand names include TNKase® and Metalyse®.
How It Works
Pharmacodynamics: Tenecteplase promotes thrombolysis (breakdown of blood clots) by catalyzing the conversion of plasminogen to plasmin. Plasmin then degrades fibrin, the main protein component of thrombi. Compared to alteplase, tenecteplase has a higher fibrin specificity, greater resistance to plasminogen activator inhibitor-1 (PAI-1), and a longer half-life.
Pharmacokinetics: Administered as an intravenous bolus, tenecteplase is primarily eliminated through hepatic metabolism and has a half-life of 20 to 25 minutes. It exhibits dose-proportional pharmacokinetics.
Mode of Action: Tenecteplase binds to fibrin within the thrombus, activating plasminogen to plasmin, which then degrades the fibrin matrix of the clot. This fibrin-specific action limits systemic plasmin generation compared to other thrombolytic agents.
Elimination Pathways: Tenecteplase is primarily cleared by the liver. It is minimally excreted renally.
Dosage
Standard Dosage
Adults:
For Acute Myocardial Infarction (AMI/STEMI): Administer as a single intravenous bolus over 5 seconds based on the patient’s 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 (maximum dose)
For acute ischemic stroke (off-label): 0.25 mg/kg as a single intravenous bolus (maximum dose 25 mg).
For acute massive pulmonary embolism: Weight-based dosing as for AMI.
Children:
The safety and efficacy of tenecteplase in pediatric patients have not been established.
Special Cases:
- Elderly Patients (≥75 years): Consider reducing the dose for AMI due to increased bleeding risk.
- Patients with Renal Impairment: No dose adjustment is typically necessary as renal clearance is minimal.
- Patients with Hepatic Dysfunction: Limited data are available, and caution is advised. Dose adjustment may be necessary.
- Patients with Comorbid Conditions: Evaluate bleeding risk carefully, particularly in patients with a history of bleeding or trauma.
Clinical Use Cases
Dosing recommendations for specific clinical use cases align with the standard adult dosing outlined above.
Dosage Adjustments:
Dose modifications should be made based on patient-specific factors like age (elderly), hepatic impairment, and bleeding risk.
Side Effects
Common Side Effects:
Bleeding (including at the injection site), nausea, vomiting, fever.
Rare but Serious Side Effects:
Intracranial hemorrhage, stroke, allergic reactions (anaphylaxis, angioedema), hypotension, arrhythmias, cardiac tamponade.
Long-Term Effects:
No specific long-term side effects have been identified for a single dose administration as indicated for AMI. Repeated use is generally not recommended.
Adverse Drug Reactions (ADR)
Serious bleeding, including intracranial hemorrhage and gastrointestinal bleeding; allergic reactions, including anaphylaxis; and stroke require urgent medical attention.
Contraindications
- Active internal bleeding
- History of cerebrovascular accident
- Recent intracranial or intraspinal surgery or trauma (within 2 months)
- Intracranial neoplasm, arteriovenous malformation, or aneurysm
- Known bleeding diathesis
- Severe uncontrolled hypertension
Drug Interactions
Tenecteplase interacts with anticoagulants (heparin, warfarin, direct oral anticoagulants), antiplatelet agents (aspirin, clopidogrel), and other medications affecting coagulation. These interactions can increase the risk of bleeding. Consult a drug interaction database for a complete list.
Pregnancy and Breastfeeding
Tenecteplase is a Pregnancy Category C drug (FDA). Animal studies have shown adverse effects. There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit outweighs the potential risk to the fetus.
It is unknown whether tenecteplase is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued for the first 24 hours after thrombolytic therapy.
Drug Profile Summary
- Mechanism of Action: Activates plasminogen to plasmin, leading to fibrinolysis and thrombolysis.
- Side Effects: Bleeding, nausea, vomiting, fever. Serious side effects: intracranial hemorrhage, stroke, allergic reactions.
- Contraindications: Active bleeding, history of stroke, recent intracranial surgery/trauma, intracranial neoplasm/AVM/aneurysm, bleeding diathesis, severe uncontrolled hypertension.
- Drug Interactions: Anticoagulants, antiplatelet agents.
- Pregnancy & Breastfeeding: Category C; use with caution. Discontinue breastfeeding for 24 hours post-administration.
- Dosage: Weight-based, single IV bolus, max 50 mg for AMI/PE; 0.25 mg/kg, max 25 mg for stroke (off-label).
- Monitoring Parameters: Signs of bleeding, neurological status, blood pressure, heart rate, ECG.
Popular Combinations
Tenecteplase is commonly administered with antiplatelet agents (e.g., aspirin) and anticoagulants (e.g., heparin) as part of AMI management.
Precautions
Standard precautions include monitoring for bleeding complications, allergic reactions, and changes in neurological status. Caution should be used in elderly patients and those with hepatic impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Tenecteplase in acute myocardial infarction?
A: The dose is weight-based and administered as a single IV bolus: <60 kg: 30 mg; 60-<70 kg: 35 mg; 70-<80 kg: 40 mg; 80-<90 kg: 45 mg; ≥90 kg: 50 mg.
Q2: What is the role of Tenecteplase in stroke management?
A: Although not FDA-approved for stroke, tenecteplase is sometimes used off-label for acute ischemic stroke at a dose of 0.25 mg/kg IV bolus (maximum 25 mg).
Q3: What are the major bleeding risks associated with Tenecteplase?
A: Intracranial hemorrhage, gastrointestinal bleeding, and bleeding at the injection site are potential bleeding complications.
Q4: What are the contraindications to Tenecteplase administration?
A: Active bleeding, stroke history, recent neurosurgery/trauma, intracranial abnormalities (neoplasm, AVM, aneurysm), bleeding disorders, and uncontrolled severe hypertension are contraindications.
Q5: How does Tenecteplase differ from Alteplase?
A: Tenecteplase has a longer half-life, higher fibrin specificity, and greater resistance to PAI-1, allowing for single bolus administration.
Q6: What are the key drug interactions with Tenecteplase?
A: Concomitant use of anticoagulants (e.g., heparin, warfarin) and antiplatelet agents (e.g., aspirin, clopidogrel) increases the risk of bleeding.
Q7: Can Tenecteplase be used in patients with renal impairment?
A: Dose adjustment is usually not necessary as renal clearance is minimal.
Q8: What are the essential monitoring parameters after Tenecteplase administration?
A: Closely monitor for signs of bleeding, neurological changes, vital signs (blood pressure, heart rate), and ECG changes.
Q9: What is the maximum dose of Tenecteplase for acute myocardial infarction?
A: The maximum recommended dose is 50 mg.
Q10: How should Tenecteplase be administered?
A: It should be administered as a single intravenous bolus over 5 seconds. It should not be administered in an IV line containing dextrose.
