Tenecteplase: Difference between revisions
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{{DrugProjectFormSinglePage | |||
|authorTag={{AL}} | |||
|genericName=Tenecteplase | |||
|aOrAn=a | |||
|drugClass=[[tissue plasminogen activator]] | |||
|indicationType=treatment | |||
|indication=[[acute myocardial infarction]] | |||
|blackBoxWarningTitle=<b><span style="color:#FF0000;">TITLE</span></b> | |||
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content) | |||
|fdaLIADAdult=====Acute Myocardial Infarction=== | |||
*The recommended total dose should not exceed 50 mg and is based upon patient weight. | |||
*A single bolus dose should be administered over 5 seconds based on patient weight. | |||
[[Image:Tenecteplase01.jpg|thumb|left|500px]] | |||
{{clr}} | |||
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Tenecteplase in adult patients. | |||
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Tenecteplase in adult patients. | |||
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Tenecteplase in pediatric patients. | |||
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Tenecteplase in pediatric patients. | |||
|contraindications=TNKase therapy in patients with acute myocardial infarction is contraindicated in the following situations because of an increased risk of bleeding (seeWARNINGS): | |||
*Active internal bleeding | |||
*History of cerebrovascular accident | |||
*Intracranial or intraspinal surgery or trauma within 2 months | |||
*Intracranial neoplasm, [[arteriovenous malformation]], or [[aneurysm]] | |||
*Known bleeding diathesis | |||
*Severe uncontrolled [[hypertension]] | |||
|warnings=====Bleeding==== | |||
The most common complication encountered during TNKase therapy is bleeding. The type of bleeding associated with thrombolytic therapy can be divided into two broad categories: | |||
*Internal bleeding, involving intracranial and retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts. | |||
*Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or sites of recent surgical intervention. | |||
Should serious bleeding (not controlled by local pressure) occur, any concomitant [[heparin]] or antiplatelet agents should be discontinued immediately. | |||
In clinical studies of TNKase, patients were treated with both aspirin and [[heparin]]. [[heparin]] may contribute to the bleeding risks associated with TNKase. The safety of the use of TNKase with other antiplatelet agents has not been adequately studied. Intramuscular injections and nonessential handling of the patient should be avoided for the first few hours following treatment with TNKase. Venipunctures should be performed and monitored carefully. | |||
Should an arterial puncture be necessary during the first few hours following TNKase therapy, it is preferable to use an upper extremity vessel that is accessible to manual compression. Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding. | |||
Each patient being considered for therapy with TNKase should be carefully evaluated and anticipated benefits weighed against potential risks associated with therapy. In the following conditions, the risk of TNKase therapy may be increased and should be weighed against the anticipated benefits: | |||
*Recent major surgery, e.g., [[coronary artery bypass graft]], obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels | |||
*Cerebrovascular disease | |||
*Recent gastrointestinal or genitourinary bleeding | |||
*Recent trauma | |||
*[[hypertension]]: systolic BP ≥180 mm Hg and/or diastolic BP ≥110 mm Hg | |||
*High likelihood of left heart thrombus, e.g., mitral stenosis with [[atrial fibrillation]] | |||
*Acute [[pericarditis]] | |||
*[[Subacute bacterial endocarditis]] | |||
*Hemostatic defects, including those secondary to severe hepatic or renal disease | |||
*Severe [[hepatic dysfunction]] | |||
*Pregnancy | |||
*Diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions | |||
*Septic thrombophlebitis or occluded AV cannula at seriously infected site | |||
*Advanced age (see PRECAUTIONS: Geriatric Use) | |||
*Patients currently receiving oral anticoagulants, e.g., warfarin sodium | |||
*Recent administration of GP IIb/IIIa inhibitors | |||
*Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location | |||
====Cholesterol Embolization==== | |||
[[Cholesterol embolism]] has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g., cardiac [[catheterization]], [[angiography]], vascular surgery) and/or anticoagulant therapy. Clinical features of [[cholesterol embolism]] may include livedo [[reticularis]], "purple toe" syndrome, [[acute renal failure]], gangrenous digits, [[hypertension]], [[pancreatitis]], [[[[myocardial infarction]]]], [[cerebral infarction]], spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis. | |||
====[[Arrhythmias]]==== | |||
Coronary thrombolysis may result in arrhythmias associated with [[reperfusion]]. These [[arrhythmias]] (such as [[sinus bradycardia]], accelerated idioventricular rhythm, ventricular premature depolarizations, [[ventricular tachycardia]]) are not different from those often seen in the ordinary course of acute [[myocardial infarction]] and may be managed with standard anti‑arrhythmic measures. It is recommended that anti‑arrhythmic therapy for [[bradycardia]] and/or ventricular irritability be available when TNKase is administered. | |||
====Use with [[Percutaneous Coronary Intervention]] ([[PCI]])==== | |||
In patients with large ST segment elevation [[myocardial infarction]], physicians should choose either thrombolysis or [[PCI]] as the primary treatment strategy for [[reperfusion]]. Rescue [[PCI]] or subsequent elective [[PCI]] may be performed after administration of thrombolytic therapies if medically appropriate; however, the optimal use of adjunctive antithrombotic and antiplatelet therapies in this setting is unknown. | |||
|clinicalTrials===Adverse Reactions== | |||
===Bleeding=== | |||
The most frequent adverse reaction associated with TNKase is bleeding. | |||
Should serious bleeding occur, concomitant heparin and antiplatelet therapy should be discontinued. Death or permanent disability can occur in patients who experience stroke or serious bleeding episodes. | |||
For TNKase-treated patients in ASSENT-2, the incidence of intracranial hemorrhage was 0.9% and any stroke was 1.8%. The incidence of all strokes, including intracranial bleeding, increases with increasing age. | |||
In the ASSENT-2 study, the following bleeding events were reported (see Table 3). | |||
{| | |||
|- | |||
|[[File:Tenecteplase04.jpg|thumb|800px]] | |||
|- | |||
|} | |||
Non-intracranial major bleeding and the need for blood transfusions were lower in patients treated with TNKase. | |||
Types of major bleeding reported in 1% or more of the patients were [[hematoma]] (1.7%) and gastrointestinal tract (1%). Types of major bleeding reported in less than 1% of the patients were urinary tract, puncture site (including cardiac catheterization site), [[retroperitoneal]], respiratory tract, and unspecified. Types of minor bleeding reported in 1% or more of the patients were [[hematoma]] (12.3%), urinary tract (3.7%), puncture site (including cardiac catheterization site) (3.6%), pharyngeal (3.1%), gastrointestinal tract (1.9%), epistaxis (1.5%), and unspecified (1.3%). | |||
===Allergic Reactions=== | |||
Allergic-type reactions (e.g., anaphylaxis, angioedema, laryngeal edema, rash, and urticaria) have rarely (< 1%) been reported in patients treated with TNKase. Anaphylaxis was reported in < 0.1% of patients treated with TNKase; however, causality was not established. When such reactions occur, they usually respond to conventional therapy. | |||
===Other Adverse Reactions=== | |||
The following adverse reactions have been reported among patients receiving TNKase in clinical trials. These reactions are frequent sequelae of the underlying disease, and the effect of TNKase on the incidence of these events is unknown. | |||
These events include cardiogenic shock, [[arrhythmias]], [[atrioventricular block]], [[pulmonary edema]], heart failure, [[cardiac arrest]], recurrent [[myocardial ischemia]], myocardial reinfarction, myocardial rupture, [[cardiac tamponade]], [[pericarditis]], [[pericardial effusion]], [[mitral regurgitation]], [[thrombosis]], [[embolism]], and [[electromechanical dissociation]]. These events can be life-threatening and may lead to death. [[Nausea]] and/or [[vomiting]],[[hypotension]], and fever have also been reported. | |||
|drugInteractions=Formal interaction studies of TNKase with other drugs have not been performed. Patients studied in clinical trials of TNKase were routinely treated with [[heparin]] and [[aspirin]]. Anticoagulants (such as [[heparin]] and vitamin K antagonists) and drugs that alter platelet function (such as [[acetylsalicylic acid]], [[dipyridamole]], and GP IIb/IIIa inhibitors) may increase the risk of bleeding if administered prior to, during, or after TNKase therapy. | |||
|alcohol=Alcohol-Tenecteplase interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. | |||
}} | |||
__NOTOC__ | __NOTOC__ | ||
{{Tenecteplase}} | {{Tenecteplase}} | ||
Revision as of 19:03, 11 July 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]
Disclaimer
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Overview
Tenecteplase is a tissue plasminogen activator that is FDA approved for the treatment of acute myocardial infarction. Common adverse reactions include {{{adverseReactions}}}.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
=Acute Myocardial Infarction
- The recommended total dose should not exceed 50 mg and is based upon patient weight.
- A single bolus dose should be administered over 5 seconds based on patient weight.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Tenecteplase in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Tenecteplase in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Tenecteplase FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Tenecteplase in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Tenecteplase in pediatric patients.
Contraindications
TNKase therapy in patients with acute myocardial infarction is contraindicated in the following situations because of an increased risk of bleeding (seeWARNINGS):
- Active internal bleeding
- History of cerebrovascular accident
- Intracranial or intraspinal surgery or trauma within 2 months
- Intracranial neoplasm, arteriovenous malformation, or aneurysm
- Known bleeding diathesis
- Severe uncontrolled hypertension
Warnings
Bleeding
The most common complication encountered during TNKase therapy is bleeding. The type of bleeding associated with thrombolytic therapy can be divided into two broad categories:
- Internal bleeding, involving intracranial and retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts.
- Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or sites of recent surgical intervention.
Should serious bleeding (not controlled by local pressure) occur, any concomitant heparin or antiplatelet agents should be discontinued immediately.
In clinical studies of TNKase, patients were treated with both aspirin and heparin. heparin may contribute to the bleeding risks associated with TNKase. The safety of the use of TNKase with other antiplatelet agents has not been adequately studied. Intramuscular injections and nonessential handling of the patient should be avoided for the first few hours following treatment with TNKase. Venipunctures should be performed and monitored carefully.
Should an arterial puncture be necessary during the first few hours following TNKase therapy, it is preferable to use an upper extremity vessel that is accessible to manual compression. Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding.
Each patient being considered for therapy with TNKase should be carefully evaluated and anticipated benefits weighed against potential risks associated with therapy. In the following conditions, the risk of TNKase therapy may be increased and should be weighed against the anticipated benefits:
- Recent major surgery, e.g., coronary artery bypass graft, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels
- Cerebrovascular disease
- Recent gastrointestinal or genitourinary bleeding
- Recent trauma
- hypertension: systolic BP ≥180 mm Hg and/or diastolic BP ≥110 mm Hg
- High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation
- Acute pericarditis
- Subacute bacterial endocarditis
- Hemostatic defects, including those secondary to severe hepatic or renal disease
- Severe hepatic dysfunction
- Pregnancy
- Diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions
- Septic thrombophlebitis or occluded AV cannula at seriously infected site
- Advanced age (see PRECAUTIONS: Geriatric Use)
- Patients currently receiving oral anticoagulants, e.g., warfarin sodium
- Recent administration of GP IIb/IIIa inhibitors
- Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location
Cholesterol Embolization
Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy. Clinical features of cholesterol embolism may include livedo reticularis, "purple toe" syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, [[myocardial infarction]], cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.
Arrhythmias
Coronary thrombolysis may result in arrhythmias associated with reperfusion. These arrhythmias (such as sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, ventricular tachycardia) are not different from those often seen in the ordinary course of acute myocardial infarction and may be managed with standard anti‑arrhythmic measures. It is recommended that anti‑arrhythmic therapy for bradycardia and/or ventricular irritability be available when TNKase is administered.
Use with Percutaneous Coronary Intervention (PCI)
In patients with large ST segment elevation myocardial infarction, physicians should choose either thrombolysis or PCI as the primary treatment strategy for reperfusion. Rescue PCI or subsequent elective PCI may be performed after administration of thrombolytic therapies if medically appropriate; however, the optimal use of adjunctive antithrombotic and antiplatelet therapies in this setting is unknown.
Adverse Reactions
Clinical Trials Experience
Adverse Reactions
Bleeding
The most frequent adverse reaction associated with TNKase is bleeding.
Should serious bleeding occur, concomitant heparin and antiplatelet therapy should be discontinued. Death or permanent disability can occur in patients who experience stroke or serious bleeding episodes.
For TNKase-treated patients in ASSENT-2, the incidence of intracranial hemorrhage was 0.9% and any stroke was 1.8%. The incidence of all strokes, including intracranial bleeding, increases with increasing age.
In the ASSENT-2 study, the following bleeding events were reported (see Table 3).
{
Postmarketing Experience
There is limited information regarding Tenecteplase Postmarketing Experience in the drug label.
Drug Interactions
Formal interaction studies of TNKase with other drugs have not been performed. Patients studied in clinical trials of TNKase were routinely treated with heparin and aspirin. Anticoagulants (such as heparin and vitamin K antagonists) and drugs that alter platelet function (such as acetylsalicylic acid, dipyridamole, and GP IIb/IIIa inhibitors) may increase the risk of bleeding if administered prior to, during, or after TNKase therapy.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Tenecteplase in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Tenecteplase in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Tenecteplase during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Tenecteplase in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Tenecteplase in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Tenecteplase in geriatric settings.
Gender
There is no FDA guidance on the use of Tenecteplase with respect to specific gender populations.
Race
There is no FDA guidance on the use of Tenecteplase with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Tenecteplase in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Tenecteplase in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Tenecteplase in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Tenecteplase in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Tenecteplase Administration in the drug label.
Monitoring
There is limited information regarding Tenecteplase Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Tenecteplase and IV administrations.
Overdosage
There is limited information regarding Tenecteplase overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Tenecteplase Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Tenecteplase Mechanism of Action in the drug label.
Structure
There is limited information regarding Tenecteplase Structure in the drug label.
Pharmacodynamics
There is limited information regarding Tenecteplase Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Tenecteplase Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Tenecteplase Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Tenecteplase Clinical Studies in the drug label.
How Supplied
There is limited information regarding Tenecteplase How Supplied in the drug label.
Storage
There is limited information regarding Tenecteplase Storage in the drug label.
Images
Drug Images
{{#ask: Page Name::Tenecteplase |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Tenecteplase |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
There is limited information regarding Tenecteplase Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Tenecteplase interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Tenecteplase Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Tenecteplase Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [4]
Synonyms / Brand Names: TNKASE®
Overview
Tenecteplase (TNK) is an enzyme used as a thrombolytic drug.
Tenecteplase is a tissue plasminogen activator (tPA) produced by recombinant DNA technology using an established mammalian cell line (Chinese hamster ovary cells). Tenecteplase is a 527 amino acid glycoprotein developed by introducing the following modifications to the complementary DNA (cDNA) for natural human tPA: a substitution of threonine 103 with asparagine, and a substitution of asparagine 117 with glutamine, both within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296–299 in the protease domain.
Tenecteplase is a recombinant fibrin-specific plasminogen activator that is derived from native t-PA by modifications at three sites of the protein structure. It binds to the fibrin component of the thrombus (blood clot) and selectively converts thrombus-bound plasminogen to plasmin, which degrades the fibrin matrix of the thrombus. Tenecteplase has a higher fibrin specificity and greater resistance to inactivation by its endogenous inhibitor (PAI-1) compared to native t-PA.
Category
Cardiovascular Drugs:Thrombolytic drugs
FDA Package Insert
| Indications and Usage | Dosage and Administration | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Use in Specific Populations | Description | Clinical Pharmacology | Nonclinical Toxicology | Clinical Studies | How Supplied/Storage and Handling | Labels and Packages