Tenecteplase

Approved Indications:

• Acute ST-Segment Elevation Myocardial Infarction (STEMI):
• Indicated for use in adults to reduce mortality associated with acute STEMI when administered within 6 hours (or up to 12 hours in some protocols) of symptom onset, in conjunction with standard antithrombotic therapy.

Clinically Accepted Off-Label Uses:

• Acute Ischemic Stroke (AIS):
• Increasingly used off-label in select patients within 4.5 hours of symptom onset as an alternative to alteplase. Shown to have similar or superior efficacy in clot resolution in major trials.
• Massive Pulmonary Embolism (PE):
• Considered for high-risk patients with hemodynamic instability, although not officially approved; used in critical care and interventional settings.
• Prosthetic Valve Thrombosis:
• Occasionally used as an alternative fibrinolytic in cases of left-sided prosthetic valve thrombosis unresponsive to other agents.

Route of Administration: Intravenous bolus only

Adults (STEMI):

• Weight-Based Single IV Bolus Over 5 Seconds:
• <60 kg: 30 mg
• 60–69.9 kg: 35 mg
• 70–79.9 kg: 40 mg
• 80–89.9 kg: 45 mg
• ≥90 kg: 50 mg (maximum dose)

Concomitant Therapy:

• Administer with anticoagulants (e.g., enoxaparin or unfractionated heparin) and antiplatelet agents (e.g., aspirin, clopidogrel).

Acute Ischemic Stroke (off-label):

• 0.25 mg/kg IV bolus (maximum 25 mg), based on clinical trial protocols (e.g., EXTEND-IA TNK).

Pediatrics:

• Safety and efficacy not established; not recommended.

Elderly:

• No specific dose adjustment required, but increased bleeding risk necessitates close monitoring.

Renal & Hepatic Impairment:

• No specific dose adjustment, but use with caution due to limited safety data and bleeding risks.

Tenecteplase is a genetically engineered fibrin-specific tissue plasminogen activator (tPA). It binds to fibrin in a thrombus and converts plasminogen to plasmin, which then degrades fibrin and dissolves the thrombus. It is a modified form of alteplase with increased fibrin specificity, longer half-life, and enhanced resistance to plasminogen activator inhibitor-1 (PAI-1). These properties allow for single-bolus dosing and more sustained thrombolytic activity at the site of the clot with reduced systemic fibrinolysis.

• Absorption: Not applicable (IV administration)
• Distribution: Volume of distribution ~6–8 L; minimal binding to plasma proteins
• Metabolism: Primarily hepatic clearance via binding to specific receptors and rapid degradation
• Half-life (t½): Approximately 20–24 minutes (biphasic), with terminal half-life ~90–130 minutes
• Excretion: Cleared via liver and reticuloendothelial system
• Elimination: Nonrenal route; not significantly affected by renal function

• Pregnancy:
• FDA Category C (older classification): Animal studies are insufficient; human data are limited. Use only if potential benefits justify potential risks, especially in life-threatening situations.
• Lactation:
• Unknown whether tenecteplase is excreted in human milk. Due to the short half-life and peptide structure, systemic absorption by infants is unlikely, but caution is advised. Temporary cessation of breastfeeding may be considered following administration.

• Primary Class: Thrombolytic Agent
• Subclass: Recombinant Fibrin-Specific Tissue Plasminogen Activator (r-tPA)
• Generation: Genetically modified third-generation thrombolytic

• Known hypersensitivity to tenecteplase or any component of the formulation
• Active internal bleeding
• History of hemorrhagic stroke or stroke of unknown origin at any time
• Ischemic stroke or transient ischemic attack within the past 3 months
• Known intracranial neoplasm, arteriovenous malformation, or aneurysm
• Recent intracranial or spinal surgery or significant head trauma
• Severe uncontrolled hypertension (>180/110 mmHg unresponsive to therapy)
• Bleeding diathesis or coagulation disorders
• Suspected aortic dissection
• Recent gastrointestinal or genitourinary bleeding

• Bleeding:
• Major risk includes intracranial hemorrhage and internal bleeding. Avoid invasive procedures and monitor closely for signs of bleeding.
• Hypersensitivity Reactions:
• Although rare, monitor for anaphylaxis or angioedema.
• Thromboembolism Post-lysis:
• Embolization of thrombotic material may occur (e.g., stroke, reinfarction).
• Reperfusion Arrhythmias:
• Common after clot lysis; monitor ECG closely during and after administration.
• Concomitant Anticoagulants:
• Increases risk of serious bleeding events; ensure appropriate timing and monitoring of heparin or antiplatelets.
• Monitoring:
• Regular assessment of blood pressure, neurological status, and bleeding parameters is essential during treatment.

Common:

• Cardiovascular: Hypotension, reperfusion arrhythmias
• Bleeding: Injection site bleeding, ecchymosis, mucosal bleeding

Serious:

• Intracranial Hemorrhage: May present as sudden neurological deterioration; life-threatening
• Gastrointestinal Bleeding: Hematemesis, melena
• Hematuria or Retroperitoneal Bleed: Especially with concurrent anticoagulants

Rare/Immunologic:

• Anaphylaxis, angioedema
• Fever, chills

Timing:

• Bleeding may occur within hours of administration; monitor intensively during the first 24 hours.

• Anticoagulants (e.g., Heparin, Enoxaparin):
• Additive bleeding risk; co-administration requires strict timing and monitoring.
• Antiplatelets (e.g., Aspirin, Clopidogrel):
• Enhances bleeding potential when used with tenecteplase as part of reperfusion therapy.
• Warfarin or DOACs:
• Contraindicated if INR is elevated or recent use increases bleeding risk.
• ACE Inhibitors:
• May increase risk of angioedema when given concomitantly.
• Food & Alcohol:
• No direct interactions, but avoid alcohol due to increased bleeding tendency.
• Enzymatic Interactions:
• Tenecteplase is not metabolized via the CYP450 system; thus, drug interaction potential via hepatic enzyme inhibition/induction is negligible.

• 2023 AHA/ASA Stroke Guidelines:
• Support off-label tenecteplase use at 0.25 mg/kg for acute ischemic stroke as an alternative to alteplase in select populations.
• ESC 2022 STEMI Guidelines:
• Reaffirm tenecteplase as preferred fibrinolytic for STEMI in patients where PCI cannot be performed within recommended timeframes.
• Ongoing Trials (as of 2024–2025):
• TNK-STROKE II and ATTEST trials evaluating tenecteplase superiority over alteplase in ischemic stroke.
• Regulatory:
• No new contraindications or major FDA safety changes in the past 12 months.

• Storage Temperature:
• Store between 2°C and 8°C (Refrigerated)
• Light & Humidity:
• Protect from light; store in original carton; do not freeze.
• Reconstitution:
• Reconstitute with accompanying sterile water for injection to a final concentration of 5 mg/mL.
• Use only provided diluent and syringe.
• Post-Reconstitution:
• Use immediately. If not used, discard after 8 hours at 2°C–8°C.
• Do not shake—gently swirl.
• Handling Precautions:
• Tenecteplase is a lyophilized protein; avoid excessive agitation.
• Use aseptic technique during reconstitution and administration.