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Alteplase
Pronunciation
U.S. Brand Names
Generic Available
Canadian Brand Names
Synonyms
Pharmacological Index
Use
Pregnancy Risk Factor
Contraindications
Warnings/Precautions
Adverse Reactions
Overdosage/Toxicology
Drug Interactions
Stability
Mechanism of Action
Pharmacodynamics/Kinetics
Usual Dosage
Reference Range
Cardiovascular Considerations
Mental Health: Effects on Mental Status
Mental Health: Effects on Psychiatric Treatment
Dental Health: Local Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental Treatment
Patient Information
Nursing Implications
Dosage Forms
References

Pronunciation
(AL te plase)

U.S. Brand Names
Activase® Injection

Generic Available

No


Canadian Brand Names
Lysatec-rt-PA®

Synonyms
Alteplase, Recombinant; Alteplase, Tissue Plasminogen Activator, Recombinant; t-PA

Pharmacological Index

Thrombolytic Agent


Use

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.


Pregnancy Risk Factor

C


Contraindications

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


Warnings/Precautions

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.


Adverse Reactions

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


Overdosage/Toxicology

Increased incidence of intracranial bleeding


Drug Interactions

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.


Stability

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)


Mechanism of Action

Initiates local fibrinolysis by binding to fibrin in a thrombus (clot) and converts entrapped plasminogen to plasmin


Pharmacodynamics/Kinetics

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


Usual Dosage

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.


Reference Range

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


Cardiovascular Considerations

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.


Mental Health: Effects on Mental Status

None reported


Mental Health: Effects on Psychiatric Treatment

None reported


Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions


Dental Health: Effects on Dental Treatment

No effects or complications reported


Patient Information

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.


Nursing Implications

Assess for hemorrhage during first hour of treatment


Dosage Forms

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)


References

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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