Tenecteplase (Monograph)

Brand name: TNKase
Drug class: Thrombolytic Agents

Medically reviewed by Drugs.com on Sep 10, 2024. Written by ASHP.

Introduction

Thrombolytic agent; biosynthetic (recombinant DNA origin) form of human tissue-type plasminogen activator (t-PA).

Uses for Tenecteplase

Acute MI

Used as a thrombolytic agent for reduction of mortality associated with acute ST-segment-elevation MI (STEMI).

Current standard of care in patients with STEMI is timely reperfusion (with primary PCI or thrombolytic therapy). The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline states that reperfusion therapy should be administered to all eligible patients with STEMI and onset of ischemic symptoms within the previous 12 hours. Select appropriate reperfusion method based on a risk-benefit analysis, considering the time from onset of MI symptoms, patient's clinical and hemodynamic status, comorbidities (e.g., severe heart failure), bleeding risk, contraindications, and availability (and timeliness) of PCI.

Primary PCI is preferred when it can be performed in a timely manner. Thrombolytic therapy is recommended when it is anticipated that PCI cannot be performed within 120 minutes of first medical contact.

Manufacturer states that in patients with large STEMI, either thrombolysis or PCI should be chosen as primary treatment strategy for reperfusion. May perform rescue PCI or subsequent elective PCI after thrombolytic therapy if medically appropriate; however, optimal use of adjunctive antithrombotic and antiplatelet therapy in this setting is unknown.

Benefits of thrombolytic therapy in patients with STEMI are well established; 30-day and 1-year mortality rates similar after tenecteplase 30–50 mg or an accelerated infusion of alteplase.

Clinical benefit diminishes as the time period from symptom onset to initiation of therapy increases. Administer as soon as possible after onset of acute MI symptoms. ACCF and AHA recommend administration within 30 minutes of hospital arrival.

Pulmonary Embolism

Has been used for the treatment of acute PE^{† [off-label]}.

The American College of Chest Physicians (ACCP) generally recommends against the use of systemic thrombolytic therapy in most patients with acute PE; however, in patients with acute PE associated with hypotension (e.g., systolic BP <90 mm Hg), thrombolytic therapy may provide some benefit in terms of mortality reduction and is suggested as a possible treatment in patients without a high risk of bleeding.

ACCP also recommends systemic thrombolytic therapy in selected patients with acute PE who clinically deteriorate after starting anticoagulant therapy but have yet to develop hypotension and who have an acceptable bleeding risk.

Acute Ischemic Stroke

Has been used for the management of acute ischemic stroke^{† [off-label]} for improving neurologic recovery and reducing the incidence of disability.

Prompt initiation of tenecteplase treatment (e.g., within 4.5 hours following onset of stroke symptoms) appears to result in reperfusion rates and favorable long-term (e.g., 3-month) functional outcomes following acute ischemic stroke that are noninferior to those seen with alteplase treatment.

Careful diagnosis and patient selection necessary to minimize risk of hemorrhage and maximize benefit. Exclude intracranial hemorrhage as primary cause of stroke signs and symptoms prior to initiation of tenecteplase.

American Heart Association (AHA)/American Stroke Association (ASA) state that IV alteplase within 4.5 hours of stroke onset remains standard of care for most patients with acute ischemic stroke. AHA/ASA state that it may be reasonable to choose tenecteplase (single 0.25-mg/kg IV bolus, maximum 25 mg) over IV alteplase in patients without contraindications for IV fibrinolysis who also are candidates to undergo mechanical thrombectomy. AHA/ASA also state that tenecteplase administered as a single 0.4-mg/kg IV bolus has not been proven to be superior or noninferior to alteplase but might be considered as an alternative to alteplase in patients with acute ischemic stroke who have minor neurological impairment and no major intracranial occlusion. However, in some studies, tenecteplase 0.4 mg/kg was associated with worse functional and safety outcomes compared to alteplase, and some clinicians recommend against use of this dosage of tenecteplase in patients with acute ischemic stroke.

Tenecteplase Dosage and Administration

General

Patient Monitoring

Monitor patients during and for several hours after tenecteplase administration for hypersensitivity reactions and treat symptoms of hypersensitivity appropriately (e.g., antihistamines, corticosteroids).

Dispensing and Administration Precautions

Based on the Institute for Safe Medication Practices (ISMP), tenecteplase is a high-alert medication that has a heightened risk of causing significant patient harm when used in error.

Other General Considerations

Initiate therapy as soon as possible after onset of acute ST-segment-elevation MI (STEMI) symptoms.
Antiarrhythmic therapy for bradycardia and/or ventricular irritability should be available when tenecteplase is administered.

Administration

IV Administration

Administer by IV injection.

Reconstitution

Reconstitute with 10 mL of sterile water for injection without preservatives to provide a solution containing 5 mg/mL of tenecteplase.

If foaming (usually slight) occurs, leave vial undisturbed for several minutes to allow dissipation of any large bubbles. Gently swirl until contents are completely dissolved; avoid shaking.

Rate of Administration

Administer over 5 seconds.

Dosage

Dose for patients with acute STEMI is based on patient weight (see Table 1); recommended total dose should not exceed 50 mg.

Adults

Acute MI

IV

Table 1. Recommended Dosage of Tenecteplase for STEMI.1
Patient Weight (kg)	Tenecteplase Dose (mg)
<60	30
≥60 to <70	35
≥70 to <80	40
≥80 to <90	45
≥90	50

Special Populations

Geriatric Patients

Although the manufacturer makes no specific dosage recommendations, some clinicians and experts suggest a 50% reduction in the dosage of tenecteplase in patients ≥75 years of age receiving the drug for acute MI.

Cautions for Tenecteplase

Contraindications

Active internal bleeding.
History of cerebrovascular accident.
Recent (within 2 months) intracranial or intraspinal surgery or trauma.
Intracranial neoplasm, arteriovenous malformation, or aneurysm.
Known bleeding diathesis.
Severe uncontrolled hypertension.

Warnings/Precautions

Effects on Hemostasis

Possible bleeding, including intracranial hemorrhage and fatal bleeding.

Risk of bleeding increased with concomitant use of other drugs that impair hemostasis.

Minimize risk of bleeding by carefully selecting patients and monitoring all potential bleeding sites (e.g., venous punctures). Avoid IM injections and unnecessary handling of patient for the first few hours following tenecteplase administration. Perform invasive arterial and venous procedures carefully and only if required. Avoid arterial and venous invasive procedures in areas that are inaccessible to manual compression (e.g., internal jugular or subclavian punctures). Use of an artery in an upper extremity is preferred if an arterial puncture is essential. Apply pressure to the puncture site for ≥30 minutes.

If serious bleeding occurs, immediately discontinue heparin and platelet-aggregation inhibitors and initiate appropriate treatment.

Results of coagulation tests and/or measures of fibrinolytic activity during tenecteplase therapy may be unreliable unless specific precautions are taken to prevent in vitro artifacts.

Thromboembolism

Possible increased risk of thromboembolic events with thrombolytic agents in patients with a high likelihood of left heart thrombus (e.g., patients with mitral stenosis or atrial fibrillation).

Cholesterol Embolization

Cholesterol embolization reported with thrombolytic agents.

In case of any new embolic event, investigate cause and treat appropriately.

Arrhythmias

Possible reperfusion-related arrhythmias (e.g., sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, ventricular tachycardia).

Manage with standard antiarrhythmic measures. Have appropriate antiarrhythmic therapy for bradycardia and/or ventricular irritability available when tenecteplase is administered.

Increased Risk of Heart Failure and Recurrent Ischemia in Combination with Planned PCI in STEMI

Trend toward worse outcomes (mortality, cardiogenic shock, CHF, recurrent MI, repeat target vessel vascularization) observed with tenecteplase plus PCI compared with PCI alone in a trial in patients with STEMI.

Manufacturer states that either thrombolysis or PCI should be chosen as the primary treatment strategy for reperfusion in patients with large STEMI. May perform rescue PCI or subsequent elective PCI after thrombolytic therapy if medically appropriate; however, optimal use of adjunctive antithrombotic and antiplatelet therapy in this setting is unknown.

Hypersensitivity Reactions

Hypersensitivity reactions, including urticarial/anaphylactic reactions (e.g., anaphylaxis, angioedema, laryngeal edema, rash, urticaria), reported.

Monitor patients during and for several hours after tenecteplase infusion. Institute appropriate therapy (e.g., antihistamines, corticosteroids) if symptoms of hypersensitivity occur.

Immunogenicity

Antibodies to tenecteplase reported.

Specific Populations

Pregnancy

No data available on tenecteplase use during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Increased risk of major birth defects not identified in small number of case reports of use of related thrombolytic agents in pregnant women.

Acute STEMI is a medical emergency that involves risks to the mother and fetus and can be fatal if left untreated. Manufacturer states not to withhold life-sustaining therapy for pregnant woman because of potential concerns regarding effects of tenecteplase on the fetus.

Lactation

Not known whether tenecteplase is distributed into human or animal milk. Possible effects on breast-fed infant or on milk production also not known.

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.

Geriatric Use

Intracranial hemorrhage, stroke, and major bleeding (i.e., bleeding requiring blood transfusions or leading to hemodynamic compromise) more frequent in tenecteplase-treated patients ≥65 years of age than in younger adults in one principal efficacy study. Increased rates of mortality at 30 days also observed in patients ≥65 years of age in this study.

In a clinical trial in patients with STEMI, an initial excess of intracranial hemorrhage observed in patients ≥75 years of age was reduced after reducing tenecteplase dose by 50%. Some clinicians and experts recommend a 50% reduction in the dosage of tenecteplase in patients ≥75 years of age receiving the drug for STEMI.

Common Adverse Effects

Bleeding and hypersensitivity reactions.

Drug Interactions

Specific Drugs

Drug	Interaction	Comments
Aspirin	Increased risk of hemorrhage	If serious bleeding occurs, discontinue aspirin and treat appropriately
Dipyridamole	Increased risk of hemorrhage	If serious bleeding occurs, discontinue dipyridamole and treat appropriately
GP IIb/IIIa inhibitors	Increased risk of hemorrhage	If serious bleeding occurs, discontinue the GP IIb/IIIa inhibitor and treat appropriately
Heparin	Increased risk of hemorrhage	If serious bleeding occurs, discontinue heparin and treat appropriately
Warfarin	Increased risk of hemorrhage	If serious bleeding occurs, discontinue warfarin and treat appropriately

Tenecteplase Pharmacokinetics

Distribution

Extent

Not known whether tenecteplase is distributed into human or animal milk.

Elimination

Metabolism

Hepatic metabolism is principal clearance mechanism.

Half-life

Initial half-life is 20–24 minutes. Terminal half-life is 90–130 minutes.

Stability

Storage

Parenteral

Powder for Injection

Controlled room temperature ≤30°C or under refrigeration at 2–8°C.

Reconstituted solutions contain no preservative. Preferably use solution immediately after preparation; may be used up to 8 hours after reconstitution if refrigerated at 2–8ºC. Discard any unused solution after 8 hours.

Actions

Binds to fibrin and converts plasminogen to plasmin.
A relatively fibrin-selective plasminogen activator. Exhibits higher fibrin selectivity and greater resistance to plasminogen-activator inhibitors (e.g., PAI-1) than alteplase.

Advice to Patients

Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses or recent surgery.
Advise patients to inform clinicians if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Tenecteplase
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For IV use only	50 mg (with sterile water for injection)	TNKase (single-dose vial; with 10 mL sterile water for injection diluent; available with BD syringe with TwinPak dual cannula device)