Pronunciation:

(AL te plase)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

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:

Pregnancy Risk Factor:

Lactation:

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

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/mm³.

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:

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:

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:

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:

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:

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:

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:

Nursing Implications:

Anesthesia and Critical Care Concerns/Other Considerations:

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:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

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

Cathflo™ Activase®: 2 mg

International Brand Names: