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Pronunciation |
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(AL
te
plase) |
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U.S. Brand
Names |
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Activase®
Injection |
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Generic
Available |
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No |
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Canadian Brand
Names |
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Lysatec-rt-PA® |
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Synonyms |
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Alteplase, Recombinant; Alteplase, Tissue Plasminogen Activator, Recombinant;
t-PA |
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Pharmacological Index |
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Thrombolytic Agent |
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Use |
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Management of acute myocardial infarction for the lysis of thrombi in
coronary arteries; management of acute massive pulmonary embolism (PE) in adults
Acute pulmonary embolism (APE): Age less than or equal to 75 years: As soon
as possible within 5 days of thrombotic event. Documented massive pulmonary
embolism by pulmonary angiography or echocardiography or high probability lung
scan with clinical shock. |
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Pregnancy Risk
Factor |
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C |
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Contraindications |
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Treatment of acute MI or PE: Active internal bleeding; history of
CVA; recent intracranial or intraspinal surgery or trauma; intracranial
neoplasm; arteriovenous malformation or aneurysm; known bleeding diathesis;
severe uncontrolled hypertension |
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Warnings/Precautions |
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Concurrent heparin anticoagulation may contribute to bleeding. Monitor all
potential bleeding sites. Doses >150 mg are associated with increased risk of
intracranial hemorrhage. Intramuscular injections and nonessential handling of
the patient should be avoided. Venipunctures should be performed carefully and
only when necessary. If arterial puncture is necessary, use an upper extremity
vessel that can be manually compressed. If serious bleeding occurs then the
infusion of alteplase and heparin should be stopped.
Coronary thrombolysis may result in reperfusion arrhythmias. In treatment of
patients with acute ischemic stroke more than 3 hours after symptom onset is not
recommended; treatment of patients with minor neurological deficit or with
rapidly improving symptoms is not recommended. |
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Adverse
Reactions |
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As with all drugs which may affect hemostasis, bleeding is the major adverse
effect associated with alteplase. 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 atrial and/or ventricular
arrhythmias.
Cardiovascular: Hypotension
Central nervous system: Fever
Dermatologic: Bruising (1%)
Gastrointestinal: GI hemorrhage (5%), nausea, vomiting
Local: Bleeding at catheter puncture site (15.3%, accelerated administration)
Hematologic: Bleeding (0.5% major, 7% minor: GUSTO trial)
Genitourinary: GU hemorrhage (4%)
<1% (Limited to important or life-threatening symptoms): Intracranial
hemorrhage (0.4% to 0.87% when dose is less than or equal to 100 mg),
retroperitoneal hemorrhage, pericardial hemorrhage, gingival hemorrhage,
epistaxis, allergic reactions: anaphylaxis, anaphylactoid reactions, laryngeal
edema, rash, and urticaria (<0.02%).
Additional cardiovascular events associated with use in myocardial
infarction: AV block, cardiogenic shock, heart failure, cardiac arrest,
recurrent ischemia/infarction, myocardial rupture, electromechanical
dissociation, pericardial effusion, pericarditis, mitral regurgitation, cardiac
tamponade, thromboembolism, pulmonary edema, asystole, ventricular tachycardia,
bradycardia, ruptured intracranial AV malformation, seizure, hemorrhagic
bursitis, cholesterol crystal embolization
Additional events associated with use in pulmonary embolism: Pulmonary
re-embolization, pulmonary edema, pleural effusion, thromboembolism
Additional events associated with use in stroke: Cerebral edema, cerebral
herniation, seizure, new ischemic stroke |
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Overdosage/Toxicology |
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Increased incidence of intracranial bleeding |
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Drug
Interactions |
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Aminocaproic acid (antifibrinolytic agent) may decrease effectiveness.
Drugs which affect platelet function (eg, NSAIDs, dipyridamole, ticlopidine,
clopidogrel, IIb/IIIa antagonists) may potentiate the risk of hemorrhage; use
with caution.
Heparin and aspirin: Use with aspirin and heparin may increase the risk of
bleeding. However, aspirin and heparin were used concomitantly with alteplase in
many patients in myocardial infarction or pulmonary embolism trials. This
combination was prohibited in the NINDS t-PA stroke trial.
Nitroglycerin may increase the hepatic clearance of alteplase, potentially
reducing lytic activity (limited clinical information).
Warfarin or oral anticoagulants: Risk of bleeding may be increased during
concurrent therapy. |
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Stability |
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The lyophilized product may be stored at room temperature (not to exceed
30°C/86°F), or under refrigeration;
once reconstituted it must be used within 8 hours
Standard dose: 100 mg/100 mL 0.9% NaCl (total volume: 200 mL)
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Mechanism of
Action |
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Initiates local fibrinolysis by binding to fibrin in a thrombus (clot) and
converts entrapped plasminogen to plasmin |
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Pharmacodynamics/Kinetics |
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Duration: >50% present in plasma is cleared within 5 minutes after the
infusion has been terminated, and ~80% is cleared within 10 minutes
Elimination: Cleared rapidly from circulating plasma at a rate of 550-650
mL/minute, primarily by the liver; >50% present in plasma is cleared within 5
minutes after the infusion has been terminated, and ~80% is cleared within 10
minutes |
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Usual Dosage |
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Coronary artery thrombi: I.V.: Front loading dose: Total dose is 100 mg over
1.5 hours (for patients who weigh <67 kg, use 1.25 mg/kg/total dose). Add
this dose to a 100 mL bag of 0.9% sodium chloride for a total volume of 200 mL.
Infuse 15 mg (30 mL) over 1-2 minutes. Infuse 50 mg (100 mL) over 30 minutes.
Begin heparin 5000-10,000 unit bolus followed by continuous infusion of 1000
units/hour. Infuse remaining 35 mg (70 mL) of alteplase over the next hour. For
less than or equal to 67 kg: 15 mg I.V. bolus over 1-2 minutes. Infuse 0.75
mg/kg (not to exceed 50 mg) over next 30 minutes and then 0.5 mg/kg over next 60
minutes (not to exceed 35 mg).
Acute pulmonary embolism: 100 mg over 2 hours.
Acute ischemic stroke: Doses should be given within the first 3 hours of the
onset of symptoms. Load with 0.09 mg/kg as a bolus, followed by 0.81 mg/kg as a
continuous infusion over 60 minutes. Maximum total dose should not exceed 90 mg.
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Reference Range |
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Not routinely measured; literature supports therapeutic levels of 0.52-1.8
mg/mL
Fibrinogen: 200-400 mg/dL
Activated partial thromboplastin time (APTT): 22.5-38.7 seconds
Prothrombin time (PT): 10.9-12.2 seconds |
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Cardiovascular
Considerations |
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The use of tissue plasminogen activator (t-PA) therapy, administered
intravenously, has shown to be of additive benefit when used in conjunction with
aspirin in a setting of myocardial infarction. Front loaded t-PA protocols
elicit a benefit greater than that seen with streptokinase therapy when patients
present early following the onset of symptoms. It is important that t-PA therapy
in myocardial infarction be accompanied by standard myocardial infarction
therapy as indicated, including beta-blocker therapy, heparin when indicated,
and ACE-inhibitor therapy. |
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Mental Health: Effects
on Mental Status |
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None reported |
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Mental Health:
Effects on Psychiatric
Treatment |
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None reported |
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Dental Health: Local
Anesthetic/Vasoconstrictor
Precautions |
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No information available to require special precautions |
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Dental Health:
Effects on Dental Treatment |
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No effects or complications reported |
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Patient
Information |
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This medication can only be administered I.V. You will have a tendency to
bleed easily following this medication; use caution to prevent injury - use
electric razor, soft toothbrush, and use caution with sharps. Strict bedrest
should be maintained to reduce the risk of bleeding. If bleeding occurs, apply
pressure to bleeding spot until bleeding stops completely. Report unusual
bruising or bleeding; blood in urine, stool, or vomitus; bleeding gums; changes
in vision; difficulty breathing; or chest pain. |
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Nursing
Implications |
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Assess for hemorrhage during first hour of treatment |
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Dosage Forms |
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Powder for injection, lyophilized (recombinant): 20 mg [11.6 million units]
(20 mL); 50 mg [29 million units] (50 mL); 100 mg [58 million units] (100
mL) |
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References |
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Astengo D, Badano L, and Bertoli D,
"Recombinant Tissue Plasminogen Activator for Prosthetic Mitral-Valve Thrombosis,"
N Engl J Med, 1995, 333(4):259.
Bell WR,
"Thrombolytic Therapy: Agents, Indications, and Laboratory Monitoring," Med
Clin North Am, 1994, 78(3):745-64.
de Boer A and van Griensven JM,
"Drug Interactions With Thrombolytic Agents. Current Perspectives," Clin
Pharmacokinet, 1995, 28(4):315-26.
Dehmer GJ, Gresalfi N, Daly D, et al,
"Impairment of Fibrinolysis by Streptokinase, Urokinase, and Recombinant Tissue-Type Plasminogen Activator in the Presence of Radiographic Contrast Agents,"
J Am Coll Cardiol, 1995, 25(5):1069-75.
Geraets DR, Hoehns JD, Burke TG, et al,
"Thrombolytic-Associated Cholesterol Emboli Syndrome: Case Report and Literature Review,"
Pharmacotherapy, 1995, 15(4):441-50.
Hagglund H, Ringden O, Ljungman P, et al,
"No Beneficial Effects, But Severe Side Effects Caused by Recombinant Human Tissue Plasminogen Activator for Treatment of Hepatic Veno-Occlusive Disease After Allogeneic Bone Marrow Transplantation,"
Transplant Proc, 1995, 27(6):3535.
Kalish SC, Gurwitz JH, Krumholz HM, et al,
"A Cost-Effectiveness Model of Thrombolytic Therapy for Acute Myocardial Infarction,"
J Gen Intern Med, 1995, 10(6):321-30.
Kurnick PB,
"Circadian Variation in the Efficacy of Tissue-Type Plasminogen Activator,"
Circulation, 1995, 91(5):1341-6.
Lam XM, Ward CA, and du Mee CP,
"Stability and Activity of Alteplase With Injectable Drugs Commonly Used in Cardiac Therapy,"
Am J Health Syst Pharm, 1995, 52(17):1904-9.
Lee TH, "Cost Effectiveness of Tissue Plasminogen Activator," N Engl J
Med, 1995, 332(21):1443-4.
Mark DB, Hlatky MA, Califf RM, et al,
"Cost Effectiveness of Thrombolytic Therapy With Tissue Plasminogen Activator as Compared With Streptokinase for Acute Myocardial Infarction,"
N Engl J Med, 1995, 332(21):1418-24.
Sloan MA, Price TR, Petito CK, et al,
"Clinical Features and Pathogenesis of Intracerebral Hemorrhage After rt-PA and Heparin Therapy for Acute Myocardial Infarction: The Thrombolysis in Myocardial Infarction (TIMI) II Pilot and Randomized Clinical Trial Combined Experience,"
Neurology, 1995, 45(4):649-58.
The Gusto Angiographic Investigators,
"The Effects of Tissue Plasminogen Activator, Streptokinase, or Both on Coronary-Artery Patency, Ventricular Function, and Survival After Acute Myocardial Infarction,"
N Engl J Med, 1993, 329(22):1615-22.
Thomas WO, Harris CN, D'Amore TF, et al,
"Bilateral Forearm and Hand Compartment Syndrome Following Thrombolysis for Acute Myocardial Infarction: A Case Report,"
J Emerg Med, 1994, 12(4):467-72.
Virk AS, Antosia RE, and Partridge RA,
"Use of Thrombolytic Therapy in a Heart Transplant Recipient With Acute Myocardial Infarction,"
Ann Emerg Med, 1995, 25(4):548-50.
White HD, "Comparative Safety of Thrombolytic Agents," Am J Cardiol,
1991, 68(16):30E-7E.
Woo KS and White HD,
"Comparative Tolerability Profiles of Thrombolytic Agents," Drug Saf,
1993, 8(1):19-29. |
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