Acute ischemic stroke (off-label use):
Note: Perform non–contrast-enhanced CT or MRI prior to administration. After ensuring eligibility criteria are met, administer within 4.5 hours of symptom onset (Campbell 2018; Logallo 2017; Menon 2022). Symptom onset is usually defined as the time last seen normal or at baseline; however, some stroke centers use imaging-based criteria for select patients who have unknown time of symptom onset (eg, wake-up or unwitnessed stroke) (Bivard 2017; Oliveira-Filho 2022; Tsivgoulis 2020). Before starting antiplatelet agents or anticoagulation, wait 24 hours after tenecteplase administration and confirm stroke is stable with no evidence of hemorrhage via a follow-up non-contrast CT (or MRI). The risk of administering antiplatelet or anticoagulant therapy within 24 hours after tenecteplase is uncertain (AHA/ASA [Powers 2019]; Oliveira-Filho 2022).
IV: 0.25 mg/kg (maximum total dose: 25 mg) once (AHA/ASA [Powers 2019]; Campbell 2018; Campbell 2020; Menon 2022).
Pulmonary embolism, acute, hemodynamically stable, intermediate to high risk (submassive) (off-label use):
Note: For most patients without hypotension, parenteral or oral anticoagulation alone is preferred over thrombolysis and anticoagulation. Systemic thrombolysis may be considered for select, younger patients with low risk of bleeding who deteriorate (eg, progressive increase in heart rate, decrease in BP, signs of shock, worsening gas exchange, progressive right heart dysfunction on echocardiography, increase in cardiac biomarkers) despite parenteral anticoagulation (ACCP [Stevens 2021]; ASH [Ortel 2020]). Some experts prefer catheter-directed therapy (CDT) if the expertise is available and the patient has a low risk of bleeding; or may consider CDT over systemic in patients with an increased risk of bleeding or with contraindications to systemic thrombolytic therapy (Weinberg 2020).
IV: Administer dose as a single bolus over 5 to 10 seconds (Kline 2014; Meyer 2014). Institute or resume parenteral anticoagulation following thrombolytic administration (ASH [Ortel 2020]; ESC [Konstantinides 2020]). Some experts start parenteral anticoagulation following thrombolytic administration when aPTT is less than twice its ULN (Weinberg 2020).
<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
Pulmonary embolism, acute, hemodynamically unstable, high risk (massive) (off-label use):
Note: Consider systemic thrombolytic therapy followed by anticoagulation over anticoagulation alone (ACCP [Stevens 2021]; ASH [Ortel 2020]). Systemic thrombolysis is generally preferred over CDT since systemic treatment can be completed more rapidly (ACCP [Stevens 2021]; ASH [Ortel 2020]; Weinberg 2020). Some experts prefer CDT, when expertise is available, if systemic thrombolytic is contraindicated or in patients with an increased bleeding risk or persistent hemodynamic instability despite systemic thrombolysis (Weinberg 2020).
IV: Administer dose as a single bolus over 5 to 10 seconds (Kline 2007; Melzer 2004). Institute or resume parenteral anticoagulation following thrombolytic administration (ASH [Ortel 2020]; ESC [Konstantinides 2020]). Some experts start parenteral anticoagulation following thrombolytic administration when aPTT is less than twice its ULN (Weinberg 2020).
<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
Pulmonary embolism associated with cardiac arrest (off-label use):
Note: Thrombolytic therapy is not recommended for routine use during cardiopulmonary arrest. May consider on a case-by-case basis (eg, suspected PE-induced cardiac arrest) (AHA [Panchal 2020]).
IV: Administer as a single bolus (Böttiger 2008; Bozeman 2006). Use therapeutic IV anticoagulation in addition to thrombolytic therapy (AHA [Lavonas 2015]; ESC [Konstantinides 2020]):
<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
ST-elevation myocardial infarction:
Note: Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy. Thrombolytic therapy is an option in centers that do not have PCI capability, followed by transfer to a PCI capable center. Administer thrombolytic therapy within 30 minutes of first medical contact (in ambulance or emergency department) if primary PCI cannot be performed within 120 minutes; if primary PCI is not available, may still consider thrombolysis in patients who present late (within 12 to 24 hours of symptom onset) and have ongoing ischemia or extensive ST elevation. Administer aspirin, clopidogrel, and anticoagulant therapy (ie, unfractionated heparin, enoxaparin, or fondaparinux) in combination with thrombolytic (ACC/AHA [O'Gara 2013]; ESC [Ibanez 2017]).
IV: Administer 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
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
Refer to adult dosing. Although dosage adjustments are not recommended, elderly patients have a higher incidence of morbidity and mortality with use of thrombolytics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Intravenous:
TNKase: 50 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Intravenous:
TNKase: 50 mg
IV: Tenecteplase is incompatible with dextrose solutions. Dextrose-containing lines must be flushed with a saline solution before and after administration. Administer as a single IV bolus over 5 seconds. Avoid IM injections and nonessential handling of patient.
PE, acute (off-label use): Administer as an IV bolus over 5 to 10 seconds using a peripheral vein (Kearon 2012; Kearon 2016).
ST-elevation myocardial infarction: Management of ST-elevation myocardial infarction for the lysis of thrombi in the coronary vasculature to restore perfusion and reduce mortality.
Acute ischemic stroke; Pulmonary embolism, acute, hemodynamically unstable, high risk (massive); Pulmonary embolism, acute, hemodynamically stable, intermediate to high risk (submassive); Pulmonary embolism associated with cardiac arrest
TNKase may be confused with Activase, t-PA
TNK (occasional abbreviation for TNKase) is an error-prone abbreviation (mistaken as TPA or TXA, error-prone abbreviation for tranexamic acid)
The Institute for Safe Medication Practices (ISMP) includes this medication (IV) among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%: Hematologic & oncologic: Hemorrhage
1% to 10%:
Cardiovascular: Cerebrovascular accident (2%)
Dermatologic: Ecchymoses
Gastrointestinal: Gastrointestinal hemorrhage
Genitourinary: Genitourinary tract hemorrhage
Hematologic & oncologic: Puncture site bleeding
Local: Bleeding at injection site
Respiratory: Epistaxis
<1%:
Cardiovascular: Cardiac arrhythmia (reperfusion; including accelerated idioventricular rhythm, asystole, atrial fibrillation, atrioventricular block, bradycardia, extrasystoles, tachycardia, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia), decreased blood pressure, embolism (including thromboembolism), hemopericardium, hemorrhagic stroke, subarachnoid hemorrhage
Hematologic & oncologic: Hematoma (cerebral, intracranial, retroperitoneal), pulmonary hemorrhage, retroperitoneal hemorrhage
Hypersensitivity: Nonimmune anaphylaxis
Immunologic: Antibody development
Nervous system: Cerebral hemorrhage, intracranial hemorrhage
Ophthalmic: Subconjunctival hemorrhage
Frequency not defined:
Cardiovascular: Cardiogenic shock, heart failure, thrombolytic drug-induced cholesterol embolism
Gastrointestinal: Nausea, vomiting
Miscellaneous: Fever
Postmarketing: Hypersensitivity: Anaphylaxis, angioedema
Treatment of ST-elevation myocardial infarction: Active internal bleeding; history of cerebrovascular accident; recent (ie, within 2 months) intracranial/intraspinal surgery or trauma; intracranial neoplasm; arteriovenous malformation or aneurysm; bleeding diathesis; severe uncontrolled hypertension.
Additional absolute contraindications (ACC/AHA [O’Gara 2013]): Ischemic stroke within 3 months; prior intracranial hemorrhage; active bleeding (excluding menses); suspected aortic dissection; significant closed head or facial trauma within 3 months.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to tenecteplase or any component of the formulation.
Treatment of pulmonary embolism (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.
Concerns related to adverse effects:
• Arrhythmias: Coronary thrombolysis may result in reperfusion arrhythmias (eg, sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, ventricular tachycardia). Antiarrhythmic therapy should be available during therapy.
• Bleeding: Internal bleeding (intracranial, retroperitoneal, gastrointestinal, genitourinary, respiratory) or external bleeding (especially at arterial and venous puncture sites) may occur. Monitor all potential bleeding sites; if serious bleeding occurs, the infusion of tenecteplase and any other concurrent anticoagulants (eg, heparin) and antiplatelets should be stopped and the patient should be treated appropriately.
• Cholesterol embolization: Cholesterol embolization has been reported rarely in patients treated with thrombolytic agents; may present as livedo reticularis, "purple toe" syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, or rhabdomyolysis and can be fatal.
• Hypersensitivity reactions: Hypersensitivity reactions (eg, anaphylaxis, urticaria, angioedema, laryngeal edema, rash) have been reported after administration. Monitor closely for hypersensitivity reactions during infusion and for several hours after; initiate appropriate therapy if symptoms of hypersensitivity occur.
• Thromboembolic events: Use may increase risk of thromboembolic events in patients with high probability of left heart thrombus (eg, patients with mitral stenosis or atrial fibrillation).
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:
• PE: Systolic BP >180 mm Hg or diastolic BP >110 mm Hg; recent bleeding (nonintracranial); recent surgery or invasive procedure; ischemic stroke >3 months previously; anticoagulated (eg, VKA therapy); traumatic CPR; pericarditis or pericardial fluid; diabetic retinopathy; age >75 years; low body weight (<60 kg); female; black (Kearon 2012; Kearon 2016); lumbar puncture within 10 days (ASRA [Horlocker 2012]).
• 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 (<3 weeks); recent internal bleeding (within 2 to 4 weeks); noncompressible vascular punctures; active peptic ulcer; oral anticoagulant therapy (ACC/AHA [O’Gara 2013]); lumbar puncture within 10 days (ASRA [Horlocker 2012]).
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]).
Special populations:
• Older adult: 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 <65 years of age, 8.5% for patients 65 to 74 years, and 16.2% for patients ≥75 years. The intracranial hemorrhage rate was 0.4% for patients <65 years, 1.6% for patients 65 to 74 years, and 1.7% for patients ≥75 years. The risks and benefits of use should be weighed carefully in the elderly.
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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Anticoagulants: Thrombolytic Agents may enhance the anticoagulant effect of Anticoagulants. Management: Monitor for signs and symptoms of bleeding if these agents are combined. For the treatment of acute ischemic stroke, avoidance with anticoagulants is often recommended, see full Lexicomp or drug interaction monograph for details. Risk C: Monitor therapy
Aprotinin: May diminish the therapeutic effect of Thrombolytic Agents. Risk C: Monitor therapy
Dabigatran Etexilate: Thrombolytic Agents may enhance the anticoagulant effect of Dabigatran Etexilate. Management: Carefully monitor for bleeding. Dabigatran Canadian labeling recommends avoiding use with thrombolytic agents. Consider avoiding alteplase treatment of acute ischemic stroke in patients receiving dabigatran (see full drug monograph for details). Risk C: Monitor therapy
Desirudin: Thrombolytic Agents may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with thrombolytic agents prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Thrombolytic Agents. Bleeding may occur. Risk C: Monitor therapy
Limaprost: May enhance the adverse/toxic effect of Thrombolytic Agents. The risk for bleeding may be increased. Risk C: Monitor therapy
Prostacyclin Analogues: Thrombolytic Agents may enhance the adverse/toxic effect of Prostacyclin Analogues. Specifically, the antiplatelet effects of prostacyclin analogues may lead to an increased risk of bleeding when combined with thrombolytic agents. Risk C: Monitor therapy
Salicylates: May enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
Tranexamic Acid: May diminish the therapeutic effect of Thrombolytic Agents. Thrombolytic Agents may diminish the therapeutic effect of Tranexamic Acid. Risk X: Avoid combination
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.
It is not known if tenecteplase is present in breast milk. The manufacturer recommends that caution be exercised when administering tenecteplase to breastfeeding women.
CBC, aPTT, signs and symptoms of bleeding, ECG monitoring
Promotes initiation of fibrinolysis by binding to fibrin and converting plasminogen to plasmin. Tenecteplase is essentially alteplase with the exception of 3 point mutations and is more fibrin specific, more resistant to plasminogen activator inhibitor -1 (PAI-1), with a longer duration of action compared to alteplase. Produced by recombinant DNA technology using a mammalian cell line (Chinese hamster ovary cells).
Distribution: Vd is weight related and approximates plasma volume
Metabolism: Primarily hepatic
Half-life elimination: Biphasic: Initial: 20 to 24 minutes; Terminal: 90 to 130 minutes
Excretion: Clearance: Plasma: 99 to 119 mL/minute
Kit (TNKase Intravenous)
50 mg (per each): $8,313.53
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