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Alteplase


Pronunciation

 (AL te plase)


U.S. Brand Names

 Activase®; Cathflo™ Activase®


Synonyms

 Alteplase, Recombinant; Alteplase, Tissue Plasminogen Activator, Recombinant; tPA


Generic Available

 No


Canadian Brand Names

 Activase® rt-PA; Cathflo™ Activase®


Use

 Management of acute myocardial infarction for the lysis of thrombi in coronary arteries; management of acute massive pulmonary embolism (PE) in adults

Acute myocardial infarction (AMI): Chest pain 20 minutes, 12-24 hours; S-T elevation 0.1 mV in at least two ECG leads

Acute pulmonary embolism (APE): Age 75 years: Documented massive pulmonary embolism by pulmonary angiography or echocardiography or high probability lung scan with clinical shock

Cathflo™ Activase®: Restoration of central venous catheter function


Use - Unlabeled/Investigational

 Acute peripheral arterial occlusive disease


Pregnancy Risk Factor

 C


Lactation

 Excretion in breast milk unknown


Contraindications

 Hypersensitivity to alteplase or any component of the formulation

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

Treatment of acute ischemic stroke: Evidence of intracranial hemorrhage or suspicion of subarachnoid hemorrhage on pretreatment evaluation; recent (within 3 months) intracranial or intraspinal surgery; prolonged external cardiac massage; suspected aortic dissection; serious head trauma or previous stroke; history of intracranial hemorrhage; uncontrolled hypertension at time of treatment (eg, >185 mm Hg systolic or >110 mm Hg diastolic); seizure at the onset of stroke; active internal bleeding; intracranial neoplasm; arteriovenous malformation or aneurysm; known bleeding diathesis including but not limited to: current use of anticoagulants or an INR >1.7, administration of heparin within 48 hours preceding the onset of stroke and an elevated aPTT at presentation, platelet count <100,000/mm 3 .

Other exclusion criteria (NINDS recombinant tPA study): Stroke or serious head injury within 3 months, major surgery or serious trauma within 2 weeks, GI or urinary tract hemorrhage within 3 weeks, aggressive treatment required to lower blood pressure, glucose level <50 mg/dL or >400 mg/dL, arterial puncture at a noncompressible site or lumbar puncture within 1 week, clinical presentation suggesting post-MI pericarditis, pregnancy; breast-feeding.


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.

For the following conditions the risk of bleeding is higher with use of thrombolytics and should be weighed against the benefits of therapy: recent major surgery (eg, CABG, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels), cerebrovascular disease, recent gastrointestinal or genitourinary bleeding, recent trauma, hypertension (systolic BP >175 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, significant hepatic dysfunction, pregnancy, diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions, septic thrombophlebitis or occluded AV cannula at seriously infected site, advanced age (eg, >75 years), patients receiving oral anticoagulants, any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of location.

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.

Cathflo™ Activase®: When used to restore catheter function, use Cathflo™ cautiously in those patients with known or suspected catheter infections. Evaluate catheter for other causes of dysfunction before use. Avoid excessive pressure when instilling into catheter. Use of Cathflo™ in children <2 years of age (or weighing <10 kg) has not been studied.


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 arrhythmia. Note: Lowest rate of bleeding complications expected with dose used to restore catheter function.

1% to 10%:

Cardiovascular: Hypotension

Central nervous system: Fever

Dermatologic: Bruising (1%)

Gastrointestinal: GI hemorrhage (5%), nausea, vomiting

Genitourinary: GU hemorrhage (4%)

Local: Bleeding at catheter puncture site (15.3%, accelerated administration)

Hematologic: Bleeding (0.5% major, 7% minor: GUSTO trial)

<1% (Limited to important or life-threatening): Intracranial hemorrhage (0.4% to 0.87% when dose is 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 MI: 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 tPA 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.


Ethanol/Nutrition/Herb Interactions

 Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, red clover, horse chestnut, garlic, green tea, ginseng, ginkgo (all have additional antiplatelet activity).


Stability

Activase®: 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. Reconstitution:

50 mg vial: Use accompanying diluent (50 mL sterile water for injection); do not shake; final concentration: 1 mg/mL

100 mg vial: Use transfer set with accompanying diluent (100 mL vial of sterile water for injection); no vacuum is present in 100 mg vial; final concentration: 1 mg/mL Alteplase is incompatible with dobutamine, dopamine, heparin, and nitroglycerin infusions; physically compatible with lidocaine, metoprolol, and propranolol when administered via Y-site; compatible with either D5W or NS. Standard dose: 100 mg/100 mL 0.9% NaCl (total volume: 200 mL)

Cathflo™ Activase®: Store lyophilized product under refrigeration; protect from excessive exposure to light when stored for extended periods of time. Reconstitution: Add 2.2 mL SWFI to vial; do not shake. Final concentration: 1 mg/mL. Once reconstituted, store at 2°C to 30°C (36°F to 86°F). Do not mix other medications into infusion solution.


Compatibility

 Stable in NS, sterile water for injection; not stable with bacteriostatic water; variable stability (consult detailed reference) in D5W

Y-site administration: Compatible: Lidocaine, metoprolol, propranolol. Incompatible: Dobutamine, dopamine, heparin, nitroglycerin

Compatibility when admixed: Compatible: Lidocaine, morphine, nitroglycerin. Incompatible: Dobutamine, dopamine, heparin


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 cleared ~5 minutes after infusion terminated, ~80% cleared within 10 minutes

Excretion: Clearance: Rapidly from circulating plasma (550-650 mL/minute), primarily hepatic; >50% present in plasma is cleared within 5 minutes after the infusion is terminated, ~80% cleared within 10 minutes


Dosage

I.V.:

Coronary artery thrombi: Front loading dose (weight-based):

Patients >67 kg: Total dose: 100 mg over 1.5 hours; infuse 15 mg over 1-2 minutes. Infuse 50 mg over 30 minutes. See "Note."

Patients 67 kg: Total dose: 1.25 mg/kg; infuse 15 mg I.V. bolus over 1-2 minutes, then infuse 0.75 mg/kg (not to exceed 50 mg) over next 30 minutes, followed by 0.5 mg/kg over next 60 minutes (not to exceed 35 mg). See "Note."

Note: Concurrently, begin heparin 60 units/kg bolus (maximum: 4000 units) followed by continuous infusion of 12 units/kg/hour (maximum: 1000 units/hour) and adjust to aPTT target of 1.5-2 times the upper limit of control. Infuse remaining 35 mg of alteplase over the next hour.

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; recommended total dose: 0.9 mg/kg (maximum dose should not exceed 90 mg) infused over 60 minutes.

Load with 0.09 mg/kg (10% of the 0.9 mg/kg dose) as an I.V. bolus over 1 minute, followed by 0.81 mg/kg (90% of the 0.9 mg/kg dose) as a continuous infusion over 60 minutes. Heparin should not be started for 24 hours or more after starting alteplase for stroke.

Intracatheter: Central venous catheter clearance: Cathflo™ Activase®:

Patients 10 to <30 kg: 110% of the internal lumen volume of the catheter ( 2 mg [1 mg/mL]); retain in catheter for 2 hours; may instill a second dose if catheter remains occluded

Patients 30 kg: 2 mg (1 mg/mL); retain in catheter for 2 hours; may instill a second dose if catheter remains occluded

Intra-arterial: Acute peripheral arterial occlusive disease (unlabeled use): 0.02-0.1 mg/kg/hour for up to 36 hours

Advisory Panel to the Society for Cardiovascular and Interventional Radiology on Thrombolytic Therapy recommendation: 2 mg/hour and subtherapeutic heparin (aPTT <1.5 times baseline)


Administration

Activase®: Acute MI: Accelerated infusion:

Bolus dose may be prepared by one of three methods:

1) removal of 15 mL reconstituted (1 mg/mL) solution from vial

2) removal of 15 mL from a port on the infusion line after priming

3) programming an infusion pump to deliver a 15 mL bolus at the initiation of infusion

Remaining dose may be administered as follows:

50 mg vial: Either PVC bag or glass vial and infusion set

100 mg vial: Insert spike end of the infusion set through the same puncture site created by transfer device and infuse from vial

If further dilution is desired, may be diluted in equal volume of 0.9% sodium chloride or D5W to yield a final concentration of 0.5 mg/mL AD

Cathflo™ Activase®: Intracatheter: Instill dose into occluded catheter. Do not force solution into catheter. After a 30-minute dwell time, assess catheter function by attempting to aspirate blood. If catheter is functional, aspirate 4-5 mL of blood to remove Cathflo™ Activase® and residual clots. Gently irrigate the catheter with NS. If catheter remains nonfunctional, let Cathflo™ Activase® dwell for another 90 minutes (total dwell time: 120 minutes) and reassess function. If catheter function is not restored, a second dose may be instilled.


Monitoring Parameters

When using for central venous catheter clearance: Assess catheter function by attempting to aspirate blood.

When using for management of acute myocardial infarction: Assess for evidence of cardiac reperfusion through resolution of chest pain, resolution of baseline ECG changes, preserved left ventricular function, cardiac enzyme washout phenomenon, and/or the appearance of reperfusion arrhythmias; assess for bleeding potential through clinical evidence of GI bleeding, hematuria, gingival bleeding, fibrinogen levels, fibrinogen degradation products, prothrombin times, and partial thromboplastin times.


Reference Range

Not routinely measured; literature supports therapeutic levels of 0.52-1.8 mcg/mL

Fibrinogen: 200-400 mg/dL

Activated partial thromboplastin time (aPTT): 22.5-38.7 seconds

Prothrombin time (PT): 10.9-12.2 seconds


Patient Education

 Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. This medication can only be administered by infusion; you will be monitored closely during and after treatment. You will have a tendency to bleed easily; use caution to prevent injury (use electric razor, soft toothbrush, and use caution with knives, needles, or anything sharp). Follow instructions for strict bedrest to reduce the risk of injury. If bleeding occurs, report immediately and apply pressure to bleeding spot until bleeding stops completely. Report unusual pain (acute headache, joint pain, chest pain); unusual bruising or bleeding; blood in urine, stool, or vomit; bleeding gums; vision changes; or respiratory difficulty. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.


Nursing Implications

 Assess for hemorrhage during first hour of treatment


Anesthesia and Critical Care Concerns/Other Considerations

 The Surgery Versus Thrombolysis for Ischemia of the Lower Extremity (STILE) trial (Ann Surg, 1994) compared surgery to intra-arterial thrombolytic therapy with either urokinase (250,000 units bolus, followed by 4000 units/minute for 4 hours, followed by 2000 units/minute for 36 hours) or alteplase (0.05 mg/kg/hour for 12 hours) in patients with acute (<14 days) or chronic peripheral arterial occlusive disease (PAOD). Patients with acute PAOD who received either fibrinolytic treatment had a shorter hospital stay and an improved amputation-free survival rate. There was no difference between alteplase or urokinase with regard to efficacy or bleeding events. A group from Stanford University recently did a retrospective comparison evaluating efficacy, safety, and cost of low-dose alteplase (<2 mg/hour) and subtherapeutic heparin to urokinase and therapeutic heparin for the treatment of PAOD or DVT (Sugimoto K, 2003). Efficacy was similar for both groups. The average dose of alteplase was 0.86 mg/hour and the dose of urokinase was 2250 units/minute. Alteplase infusions were shorter and less expensive than urokinase.


Cardiovascular Considerations

ST-Elevation Myocardial Infarction: The 2004 ACC/AHA guidelines for the management of patients with acute myocardial infarction recommend prehospital thrombolysis in special circumstances (eg, transport time >30 minutes). Efforts to quickly identify and safely treat appropriate candidates for therapy continue. Reducing treatment delays is very important to improve mortality. Thrombolytic therapy is indicated in patients with ST-segment elevation of >1 mm in two or more contiguous leads or at least 2 adjacent limb leads in patients with chest discomfort >30 minutes but 12 hours. Patients with chest discomfort suggestive of ischemia and new-onset left bundle branch block (LBBB) are also candidates for thrombolysis. Generally there is only a small trend for benefit of therapy after a delay of more than 12-24 hours, but thrombolysis may be considered for selected patients with ongoing ischemic pain and extensive ST elevation. Additional absolute contraindications for fibrinolysis use in ST-elevation myocardial infarction from the 2004 ACC/AHA guidelines: Any prior intracranial hemorrhage, ischemic stroke within 3 months (except one within 3 hours), significant closed head or facial trauma within 3 months. Additional relative contraindications include history of chronic severe, poorly-controlled hypertension, severe uncontrolled hypertension on presentation (systolic BP >180 mm Hg or diastolic >110 mm Hg; could be an absolute contraindication in low-risk patients), history of prior ischemic stroke > 3 months, dementia, or known intracranial pathology, traumatic or prolonged (>10 minutes) CPR or major surgery (<3 weeks), recent (within 2-4 weeks) internal bleeding, noncompressible vascular punctures, pregnancy, active peptic ulcer, current use of anticoagulants.

Thrombolytic and GP IIb/IIIa Inhibitor: In the GUSTO V trial, patients with acute MI were randomized to standard-dose reteplase or half-dose reteplase (two boluses of 5 units each, 30 minutes apart) and full dose abciximab. Thirty-day mortality (primary endpoint) was similar in both groups. The combination treatment group had fewer deaths or nonfatal reinfarctions, less need for urgent revascularization, fewer major ischemic complications. More bleeding occurred in the combination treatment group, but intracranial hemorrhage and nonfatal disabling stroke were similar in both groups. All cause mortality at one year was similar in both groups. In TIMI 14, the combination of full-dose abciximab (0.25 mg/kg bolus followed by a 12-hour infusion of 0.125 mcg/kg/minute, maximum 10 mcg/minute) and half-dose alteplase (15 mg bolus followed by 35 mg infusion over 60 minutes) resulted in 74% of patients achieving TIMI grade 3 flow at 90 minutes. The 2004 ACC/AHA guidelines for the management of patients with acute myocardial infarction suggests that abciximab and half-dose reteplase or tenecteplase may be considered for prevention of reinfarction in patients with an anterior MI, who <75 years of age and have no risk factors for bleeding.


Dental Health: Effects on Dental Treatment

 Key adverse event(s) related to dental treatment: 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.


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions


Mental Health: Effects on Mental Status

 None reported


Mental Health: Effects on Psychiatric Treatment

 None reported


Dosage Forms

 Injection, powder for reconstitution, recombinant:

Activase®: 50 mg [29 million int. units]; 100 mg [58 million int. units]

Cathflo™ Activase®: 2 mg


References

"A Comparison of Continuous Infusion of Alteplase With Double-Bolus Administration for Acute Myocardial Infarction. The Continuous Infusion Versus Double-Bolus Administration of Alteplase (COBALT) Investigators," N Engl J Med , 1997, 337(16):1124-30.

"A Comparison of Reteplase With Alteplase for Acute Myocardial Infarction. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators," N Engl J Med , 1997, 337(16):1118-23.

Albers GW, Bates VE, Clark WM, et al, "Intravenous Tissue-Type Plasminogen Activator for Treatment of Acute Stroke: The Standard Treatment With Alteplase to Reverse Stroke (STARS) Study," JAMA , 2000, 283(9):1145-50.

Antman EM, Anbe SC, Alpert JS, et al, "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)," Circulation , 2004, 110:588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed August 26, 2004.

Antman EM, Giugliano RP, Gibson CM, et al, "Abciximab Facilitates the Rate and Extent of Thrombolysis: Results of the Thrombolysis in Myocardial Infarction (TIMI) 14 Trial. The TIMI 14 Investigators," Circulation , 1999, 99(21):2720-32.

Clark WM, Wissman S, Albers GW, et al, "Recombinant Tissue-Type Plasminogen Activator (Alteplase) for Ischemic Stroke 3 to 5 Hours After Symptom Onset: The ATLANTIS Study: A Randomized Controlled Trial," JAMA , 1999, 282(21):2019-26.

Comerota AJ and Schmieder FA, "Intraoperative Lytic Therapy: Agents and Methods of Administration," Semin Vasc Surg , 2001, 14(2):132-42.

Gerlach AT and Pickworth KK, "Use of Alteplase in Peripheral Arterial Occlusions: Outcomes and Complications," Abstracts of the American College of Clinical Pharmacy Annual Meeting, Los Angeles, 2000, November 5-8; Abs No 47.

Kwiatkowski TG, Libman RB, Frankel M, et al, "Effects of Tissue Plasminogen Activator for Acute Ischemic Stroke at One Year. National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Group," N Engl J Med , 1999, 340(23):1781-7.

Leonard MC and Shermock KM, "Using Efficacy, Safety, and Cost Data to Support a Formulary Decision Regarding Thrombolytic Therapy," Semin Vasc Surg , 2001, 14(2):150-5.

Lincoff AM, Califf RM, Van de Werf F, et al, "Mortality at 1 Year With Combination Platelet Glycoprotein IIb/IIIa Inhibition and Reduced-Dose Fibrinolytic Therapy vs Conventional Fibrinolytic Therapy for Acute Myocardial Infarction: GUSTO V Randomized Trial," JAMA , 2002, 288(17):2130-5.

Lundergan CF, Reiner JS, McCarthy WF, et al, "Clinical Predictors of Early Infarct-Related Artery Patency Following Thrombolytic Therapy: Importance of Body Weight, Smoking History, Infarct-Related Artery and Choice of Thrombolytic Regimen: The GUSTO-I Experience. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries," J Am Coll Cardiol , 1998, 32(3):641-7.

"NINDS tPA Stroke Study Group. Generalized Efficacy for Acute Stroke: Subgroup Analysis of the NINDS tPA Stroke Study Group," Stroke , 1997, 28(11):2119-25.

Ouriel K, "Current Status of Thrombolysis for Peripheral Arterial Occlusive Disease," Ann Vasc Surg , 2002, 16(6):797-804.

Ponec D, Irwin D, Haire WD, et al, "Recombinant Tissue Plasminogen Activator (Alteplase) for Restoration of Flow in Occluded Central Venous Access Devices: A Double-Blind Placebo-Controlled Trial - The Cardiovascular Thrombolytic to Open Occluded Lines (COOL) Efficacy Trial," J Vasc Interv Radiol , 2001, 12(8):951-5.

"Results of a Prospective, Randomised Trial Evaluating Surgery Versus Thrombolysis for Ischemia of the Lower Extremity. The STILE Trial," Ann Surg , 1994, 220(3):251-66; discussion 266-8.

Semba CP, Murphy TP, Bakal CW, et al, "Thrombolytic Therapy With Use of Alteplase (rtPA) in Peripheral Arterial Occlusive Disease: Review of the Clinical Literature. The Advisory Panel," J Vasc Interv Radiol , 2000, 11(2 Pt 1):149-61.

"Sixth ACCP Consensus Conference on Antithrombotic Therapy," Chest , 2001, 119(Suppl):1-370.

Sugimoto K, Hofmann LV, Razavi MK, et al, "The Safety, Efficacy, and Pharmacoeconomics of Low-Dose Alteplase Compared With Urokinase for Catheter-Directed Thrombolysis of Arterial and Venous Occlusions," J Vasc Surg , 2003, 37(3):512-7.

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.

"The NINDS tPA Stroke Study Group. Intracerebral Hemorrhage After Intravenous tPA Therapy for Ischemic Stroke," Stroke , 1997, 28:2109-18.

"Tissue Plasminogen Activator for Acute Ischemic Stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group," N Engl J Med , 1995, 333(24):1581-7.

"Thrombolysis in the Management of Lower Limb Peripheral Arterial Occlusion - A Consensus Document. Working Party on Thrombolysis in the Management of Limb Ischemia," Am J Cardiol , 1998, 81(2):207-18.

Topol EJ, "Reperfusion Therapy for Acute Myocardial Infarction With Fibrinolytic Therapy or Combination Reduced Fibrinolytic Therapy and Platelet Glycoprotein IIb/IIIa Inhibition: The GUSTO V Randomized Trial. GUSTO V Investigators," Lancet , 2001, 357(9272):1905-14.

Valji K, "Evolving Strategies for Thrombolytic Therapy of Peripheral Vascular Occlusion," J Vasc Interv Radiol , 2000, 11(4):411-20.

Zacharias JM, Weatherston CP, Spewak CR, et al, "Alteplase Versus Urokinase for Occluded Hemodialysis Catheters," Ann Pharmacother , 2003, 37(1):27-33.


International Brand Names

 Actilyse® (AR, AT, AU, BE, BR, CH, CL, CO, CZ, DE, DK, ES, FI, FR, GB, HK, HR, HU, ID, IE, IL, IN, LU, MX, NL, NO, NZ, PL, RO, RU, SE, SG, TH, TR, YU, ZA); Activacin® (JP); Activase® rt-PA (CA); Actiylise® (SI); Cathflo™ Activase® (CA); Grtpa® (JP)


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