Tenecteplase

B01A - Antithrombotic agents ATC B01AD11 Enzyme approved 2000 Parenteral

JFDA label: Metalyse Vial 10.000 I.U (50mg) Powder and Solvent for solution for injection (Vial)

Mechanism of Action

Exogenous Protein of Tissue-type plasminogen activator — Tissue-type plasminogen activator exogenous protein

Target	Action	Gene / class
Tissue-type plasminogen activator efficacy	EXOGENOUS PROTEIN	PLAT

Indications

Approved

Recommended criteria for treatment of STEMI (ACC/AHA [O’Gara 2013])
ST-elevation myocardial infarction
STEMI ECG definition

Off-label

Pulmonary embolism associated with cardiac arrest
Pulmonary embolism, acute (hemodynamically stable/submassive)
Pulmonary embolism, acute (hemodynamically unstable/massive)

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Hypersensitivity to tenecteplase or any component of the formulation. Treatment of PE (off-label): Structural intracranial disease, previous intracranial hemorrhage, ischemic stroke within 3 months, active bleeding, recent brain or spinal surgery, recent head trauma with fracture or brain injury, bleeding diathesis Absolute
Treatment of STEMI: Active internal bleeding Absolute
active bleeding (excluding menses) Absolute
arteriovenous malformation or aneurysm Absolute
bleeding diathesis Absolute
history of cerebrovascular accident Absolute
intracranial neoplasm Absolute
prior intracranial hemorrhage Absolute
recent (ie, within 2 months) intracranial/intraspinal surgery or trauma Absolute
severe uncontrolled hypertension Additional absolute contraindications (ACC/AHA [O’Gara 2013]): Ischemic stroke within 3 months Absolute
significant closed head or facial trauma within 3 months Absolute
suspected aortic dissection Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (16)

Common Cerebrovascular accident

Not Known Atrioventricular block · cardiac arrhythmia · cardiac failure · cardiac tamponade · cardiogenic shock · embolism · hypotension · ischemic heart disease (recurrent) · mitral valve insufficiency (regurgitation) · myocardial reinfarction · myocardial rupture · pericardial effusion · pericarditis · pulmonary edema · thrombosis

Renal and urinary disorders (1)

Common Genitourinary tract hemorrhage, epistaxis

Blood and lymphatic system disorders (2)

Very Common hematoma · Hemorrhage

Gastrointestinal disorders (3)

Common Gastrointestinal hemorrhage

Not Known Nausea · vomiting

General disorders and administration site conditions (1)

Not Known Fever

Dosing

Source: Lexicomp

Pulmonary embolism, acute (hemodynamically unstable/massive) (off-label use): IV: Administer dose as a single bolus over 5 to 10 seconds (Kline 2007; Melzer 2004): ≥60 to ≥70 to ≥80 to ≥90 kg: 50 mg Pulmonary embolism, acute (hemodynamically stable/submassive) (off-label use): Note: Not recommended for most patients with acute PE without hypotension; use only in select patients showing signs of clinical deterioration despite maintaining a systolic BP >90 mm Hg where benefits outweigh risks (Kearon 2012; Kearon 2016). IV: Administer dose as a single bolus over 5 to 10 seconds (Kline 2007; Kline 2014; Melzer 2004; Meyer 2014): ≥60 to ≥70 to ≥80 to ≥90 kg: 50 mg Pulmonary embolism associated with cardiac arrest (off-label use): IV: Administer as a single bolus over 5 seconds (Böttiger 2008; Bozeman 2006): ≥60 to ≥70 to ≥80 to ≥90 kg: 50 mg STEMI: IV: The recommended total dose should not exceed 50 mg and is based on weight. Administer as a single bolus over 5 seconds: ≥60 to ≥70 to ≥80 to ≥90 kg: 50 mg Note: Thrombolytic should be administered within 30 minutes of hospital arrival. Generally, there is only a small trend for benefit of therapy after a delay of 12 to 24 hours from symptom onset, but thrombolysis may be considered for selected patients with ongoing ischemic pain and extensive ST elevation; however, primary PCI is preferred in these patients. Administer concurrent aspirin, clopidogrel, and anticoagulant therapy (ie, unfractionated heparin, enoxaparin, or fondaparinux) with tenecteplase (O’Gara 2013).

Refer to adult dosing. Although dosage adjustments are not recommended, the elderly have a higher incidence of morbidity and mortality with the use of tenecteplase.

No dosage adjustment necessary. Hemodialysis: Dialyzable: Unknown, but unlikely (NCS/SCCM [Frontera 2016])

Mild to moderate impairment: No dosage adjustment provided in manufacturer's labeling. Severe impairment: No dosage adjustment provided in manufacturer's labeling; weigh the risk of bleeding against the benefits with tenecteplase especially in those with a coagulopathy.

Warnings & Precautions

Source: Lexicomp

Arrhythmias

Coronary thrombolysis may result in reperfusion arrhythmias.

Bleeding

Monitor all potential bleeding sites. If serious bleeding occurs, the infusion of tenecteplase and heparin should be stopped. Disease-related concerns:

Conditions that increase bleeding risk

For the following conditions, the risk of bleeding is higher with use of thrombolytics and should be weighed against the benefits of therapy:

STEMI

History of chronic, severe, poorly controlled hypertension; significant hypertension on presentation (systolic BP >180 mm Hg or diastolic BP >110 mm Hg); history of prior ischemic stroke >3 months; dementia; traumatic or prolonged CPR (>10 minutes); major surgery ( Concurrent drug therapy issues:

Anticoagulants

Use with caution in patients receiving oral anticoagulants; increased risk of bleeding. Adjunctive use of parenteral anticoagulants (eg, enoxaparin, heparin, or fondaparinux) is recommended in STEMI patients to improve vessel patency and prevent reocclusion and may also contribute to bleeding; monitor for bleeding (ACC/AHA [O’Gara 2013]).

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Elderly

Use with caution in patients with advanced age; increased risk of bleeding. The 30-day mortality in the ASSENT-2 trial of AMI patients was 2.5% for patients • Pregnancy: Use with caution in pregnancy; increased risk of bleeding. Other warnings/precautions:

Administration

Avoid intramuscular injections and nonessential handling of the patient for a few hours after administration. Venipunctures should be performed carefully and only when necessary. If arterial puncture is necessary, use an upper extremity vessel that can be manually compressed. Caution with readministration of tenecteplase.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events have been observed in some animal reproduction studies. The risk of bleeding may be increased in pregnant women. Administer to pregnant women only if the potential benefits justify the risk to the fetus.

Lactation

It is not known if tenecteplase is present in breast milk. The manufacturer recommends that caution be exercised when administering tenecteplase to breastfeeding women.

Monitoring

Clinical pearl	CBC, aPTT, signs and symptoms of bleeding, ECG monitoring

Biology & Pharmacokinetics

Pharmacokinetics

Half-life	Biphasic: Initial: 20 to 24 minutes; Terminal: 90 to 130 minutes

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Abciximab	major
Acalabrutinib	major
Anisindione	major
Apixaban	major
Ardeparin	major
Argatroban	major
Avapritinib	major
Betrixaban	major
Bivalirudin	major
Cabozantinib	major
Cangrelor	major
Caplacizumab	major
Dalteparin	major
Danaparoid	major
Dasatinib	major
Deferasirox	major
Defibrotide	major
Desirudin	major
Dicoumarol	major
Drotrecogin alfa	major
Edoxaban	major
Enoxaparin	major
Eptifibatide	major
Fondaparinux	major
Heparin	major
Ibritumomab tiuxetan	major
Ibrutinib	major
Inotersen	major
Lepirudin	major
Omacetaxine mepesuccinate	major
Panobinostat	major
Ponatinib	major
Prasugrel	major
Ramucirumab	major
Regorafenib	major
Rivaroxaban	major
Tinzaparin	major
Tipranavir	major
Tirofiban	major
Tositumomab	major

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Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Metalyse Vial 10.000 I.U (50mg) Powder and Solvent for solution for injection (Vial)	Powder for Injection 50 mg	1 PFS	The Jordan Drugstore Co	—