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Tenecteplase

Pronunciation

(ten EK te plase)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Intravenous:

TNKase: 50 mg

Brand Names: U.S.

  • TNKase

Pharmacologic Category

  • Thrombolytic Agent

Pharmacology

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

Excretion

Clearance: Plasma: 99-119 mL/minute

Half-Life Elimination

Biphasic: Initial: 20-24 minutes; Terminal: 90-130 minutes

Use: Labeled Indications

Management of ST-elevation myocardial infarction (STEMI) for the lysis of thrombi in the coronary vasculature to restore perfusion and reduce mortality.

Recommended criteria for treatment of STEMI (ACCF/AHA; O’Gara, 2013): Ischemic symptoms within 12 hours of treatment or evidence of ongoing ischemia 12-24 hours after symptom onset with a large area of myocardium at risk or hemodynamic instability.

STEMI ECG definition: New ST-segment elevation at the J point in at least 2 contiguous leads of ≥2 mm (0.2 mV) in men or ≥1.5 mm (0.15 mV) in women in leads V2-V3 and/or of ≥1 mm (0.1 mV) in other contiguous precordial leads or limb leads on ECG. New or presumably new left bundle branch block (LBBB) may interfere with ST-elevation analysis and should not be considered diagnostic in isolation.

At non-PCI-capable hospitals, the ACCF/AHA recommends thrombolytic therapy administration when the anticipated first medical contact (FMC)-to-device time at a PCI-capable hospital is >120 minutes due to unavoidable delays.

Contraindications

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 contraindications (ACCF/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

Dosing: Adult

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 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

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).

Dosing: Geriatric

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.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

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.

Reconstitution

Tenecteplase should be reconstituted using the supplied 10 mL syringe with TwinPak™ Dual Cannula Device and 10 mL sterile water for injection. Do not shake when reconstituting. Slight foaming is normal and will dissipate if left standing for several minutes. The reconstituted solution is 5 mg/mL. Any unused solution should be discarded. If reconstituted and not used immediately, store in refrigerator and use within 8 hours.

Administration

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.

Compatibility

Incompatible with dextrose solutions.

Storage

Store under refrigeration of 2°C to 8°C (36°F to 46°F) or at room temperature; do not exceed 30°C (86°F). If reconstituted and not used immediately, store in refrigerator and use within 8 hours.

Drug Interactions

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Anticoagulants: Thrombolytic Agents may enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy

Aprotinin: May diminish the therapeutic effect of Thrombolytic Agents. Consider therapy modification

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). 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. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Thrombolytic Agents. Bleeding may occur. Consider therapy modification

Limaprost: May enhance the adverse/toxic effect of Thrombolytic Agents. The risk for bleeding may be increased. 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. Monitor therapy

Salicylates: May enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Monitor therapy

Test Interactions

Altered results of coagulation and fibrinolytic activity tests

Adverse Reactions

As with all drugs which may affect hemostasis, bleeding is the major adverse effect associated with tenecteplase. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the dosage administered, concurrent use of multiple agents which alter hemostasis, and patient predisposition. Rapid lysis of coronary artery thrombi by thrombolytic agents may be associated with reperfusion-related arterial and/or ventricular arrhythmia.

>10%:

Local: Hematoma (12% minor)

Hematologic: Bleeding (22% minor: ASSENT-2 trial)

1% to 10%:

Central nervous system: Stroke (2%)

Gastrointestinal: Epistaxis (2% minor), GI hemorrhage (1% major, 2% minor)

Genitourinary: GU bleeding (4% minor)

Hematologic: Bleeding (5% major; ASSENT-2 trial)

Local: Bleeding at catheter puncture site (4% minor), hematoma (2% major)

Respiratory: Pharyngeal (3% minor)

<1% (Limited to important or life-threatening): Anaphylaxis, angioedema, bleeding at catheter puncture site (<1% major), cholesterol embolism (clinical features may include livedo reticularis, “purple toe” syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, MI, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, rhabdomyolysis), GU bleeding (<1% major), intracranial hemorrhage (0.9%), laryngeal edema, rash, respiratory tract bleeding, retroperitoneal bleeding, urticaria

Additional cardiovascular events associated with use in MI: Arrhythmia, AV block, cardiac arrest, cardiac tamponade, cardiogenic shock, embolism, electromechanical dissociation, fever, heart failure, hypotension, mitral regurgitation, myocardial reinfarction, myocardial rupture, nausea, pericardial effusion, pericarditis, pulmonary edema, recurrent myocardial ischemia, thrombosis, vomiting

Warnings/Precautions

Concerns related to adverse effects:

• 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 tenecteplase and the use of tenecteplase should be weighed against the benefits of therapy: recent (within 10 days) major surgery (eg, CABG, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels), cerebrovascular disease, recent (within 10 days) gastrointestinal or genitourinary bleeding, recent trauma (within 10 days) including CPR, hypertension (systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg), high likelihood of left heart thrombus (eg, mitral stenosis with atrial fibrillation), acute pericarditis, subacute bacterial endocarditis, hemostatic defects including ones caused by severe renal or hepatic dysfunction, severe hepatic dysfunction, pregnancy, diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions, septic thrombophlebitis or occluded AV cannula at seriously infected site, and/or any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of location.

• Appropriate use: Follow standard management for ST-elevation myocardial infarction (STEMI) while administering tenecteplase.

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 to improve vessel patency and prevent reocclusion and may also contribute to bleeding; monitor for bleeding (ACCF/AHA; O’Gara, 2013).

• GP IIb/IIIa inhibitors: Use tenecteplase with caution in patients who had recent administration of GP IIb/IIIa inhibitors; bleeding risk increased.

Special populations:

• Elderly: Use with caution in patients with advanced age; increased risk of bleeding. The 30-day mortality in the ASSENT-2 trial was 2.5% for patients <65 years of age, 8.5% for patients 65-74 years, and 16.2% for patients ≥75 years. The intracranial hemorrhage rate was 0.4% for patients <65 years, 1.6% for patients 65-74 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.

Monitoring Parameters

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

Pregnancy Risk Factor

C

Pregnancy Considerations

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.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums, abnormal vaginal bleeding, bruises without a reason or that get bigger, or any bleeding that is very bad or that will not stop), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, or weight gain), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), angina, severe headache, severe abdominal pain, skin discoloration, vision changes, muscle pain, dark urine, arrhythmia, or bradycardia (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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