Trade Names:Activase- Powder for injection, lyophilized 50 mg (29 million units)- Powder for injection, lyophilized 100 mg (58 million units)
Trade Names:Cathflo Activase- Powder for injection, lyophilized 2 mgActivase rt-PA (Canada)Cathflo (Canada)
Aids in dissolution of blood clots.
C max is 3 to 4 mg/L.
Vd is 2.8 to 4.6 L and doubles at steady state.
Initial t ½ is less than 5 min. Plasma Cl is 380 to 570 mL/min; total body Cl is 34.3 to 38.4 L/h. More than 80% is cleared from plasma within 10 min.
Lysis of thrombi in management of acute MI or acute massive pulmonary embolism, management of acute ischemic stroke ( Activase only). Restoration of function to central venous access device as assessed by the ability to withdraw blood ( Cathflo Activase only).
Active internal bleeding; history of cerebrovascular accident; intracranial hemorrhage; recent (within 3 mo) intracranial or intraspinal surgery or trauma; recent previous stroke; seizure at the onset of stroke; intracranial neoplasm; arteriovenous malformation or aneurysm; bleeding diathesis; severe uncontrolled hypertension; evidence of intracranial hemorrhage on pretreatment evaluation; suspicion of subarachnoid hemorrhage; uncontrolled hypertension at time of treatment; current use of oral anticoagulants; prothrombin time longer than 15 sec, administration of heparin within 48 h preceding stroke onset with an elevated activated partial thromboplastin time at presentation; platelet count below 100,000/mm 3 .
IV The recommended dose is 0.9 mg/kg (max, 90 mg) infused over 60 min with 10% of the total dose administered as an initial IV bolus over 1 min. The safety and efficacy of this regimen with coadministration of heparin and aspirin during the first 24 h after symptom onset has not been investigated. Doses 0.9 mg/kg may be associated with an increased incidence of ICH. Do not use doses more than 0.9 mg/kg (max, 90 mg).Acute MI
Administer as soon as possible after the onset of symptoms. Do not use a dose of 150 mg because it has been associated with an increase in intracranial bleeding.Accelerated infusion
The recommended dose is based upon patient weight; do not exceed 100 mg. For patients weighing more than 67 kg, the recommended dose administered is 100 mg as a 15 mg IV bolus, followed by 50 mg infused over the next 30 min and then 35 mg infused over the next 60 min. For patients weighing 67 kg or less, the recommended dose is administered as a 15 mg IV bolus, followed by 0.75 mg/kg infused over the next 30 min not to exceed 50 mg and then 0.5 mg/kg over the next 60 min not to exceed 35 mg. (The safety and efficacy of this accelerated infusion of alteplase regimen has only been investigated with coadministration of heparin and aspirin).3-h infusion
100 mg given as 60 mg (34.8 million units) in the first hour (with 6 to 10 mg given as a bolus over the first 1 to 2 min), 20 mg (11.6 million units) over the second hour and 20 mg (11.6 million units) over the third hour. For smaller patients (less than 65 kg), use a dose of 1.25 mg/kg given over 3 h as described above.Coadministration
Although the use of anticoagulants during and following alteplase has been shown to be of equivocal benefit, heparin has been given concomitantly for at least 24 h in more than 90% of patients. Aspirin or dipyridamole has been given during or following heparin treatment.Pulmonary EmbolismAdults
IV 100 mg administered over 2 h. Initiate or reinstate heparin therapy near the end of or immediately following the alteplase infusion when the partial thromboplastin time or thrombin time returns to twice normal or less.Restoration of Function to Central Venous Catheter ( Cathflo Activase only)Adults
IV Instill into dysfunctional catheter at a concentration of 1 mg/mL. For patients weighing 30 kg or more, use 2 mg/2 mL; for patients weighing 10 kg or more to less than 30 kg, use 110% of the internal lumen volume of the catheter (max, 2 mg/2 mL). If catheter function is not restored in 120 min after 1 dose, a second dose may be instilled.
Store unopened vials in refrigerator (36° to 46°F). Fifty and 100 mg vials may also be stored at controlled room temperature (less than 86°F). Protect from excessive exposure to light. Reconstituted solution may be stored for up to 8 h in refrigerator (36° to 46°F) or at controlled room temperature (less than 86°F).
May increase the risk of bleeding.Nitroglycerin
May reduce alteplase concentrations, decreasing the thrombolytic effect.
Do not add other medications to infusion solution.
Results of tests for coagulation or fibrinolytic activity may be unreliable because of degradation of fibrinogen in blood.
All strokes (2%); arrhythmia; AV block; cardiogenic shock; heart failure; cardiac arrest; recurrent ischemia; myocardial reinfarction; myocardial rupture; electromechanical dissociation; pericardial effusion; pericarditis; mitral regurgitation; cardiac tamponade; thromboembolism; pulmonary edema; hypotension; pulmonary re-embolization.Cathflo Activase
Venous thrombosis; major hemorrhage; intracranial hemorrhage; pulmonary emboli; upper extremity deep vein thrombosis.
Cerebral edema; cerebral herniation; seizure.
Ecchymosis (1%); injection-site hemorrhage.
Bleeding (5%); nausea; vomiting.
Allergic-type reactions (eg, anaphylactoid reactions, laryngeal edema, orolingual angioedema, rash, urticaria).
Fever; pleural effusion.Cathflo Activase
Most frequent and serious adverse reaction. Monitor patient for signs of internal and superficial bleeding throughout therapy, paying particular attention to recent puncture and cutdown sites. If bleeding develops (epistaxis, hematuria, hematemesis, bloody or black, tarry stools) notify health care provider immediately. Should uncontrollable bleeding occur, discontinue alteplase therapy and concurrent heparin. Be prepared to administer protamine to reverse heparin effects.
Category C .
Safety and efficacy not established ( Activase ); safety and efficacy in children younger than 2 yr of age or who weigh less than 10 kg have not been established ( Cathflo Activase ).
There is no experience with readministration of alteplase.
Do not use 50 mg vial if vacuum is not present.
Risk of alteplase therapy to treat acute ischemic stroke may be increased by severe neurological deficit at presentation and major early infarct on a CT scan and should be weighed against the benefit.
In patients who are at low risk of death from cardiac causes and who have high BP at time of presentation, risk of stroke may offset survival benefit produced by thrombolytic therapy.
Avoid IM injections, noncompressible arterial punctures, internal jugular and subclavian venous punctures, and nonessential handling of patient during treatment. Perform venipunctures carefully and as infrequently as possible during therapy.
May occur rarely in patients treated with thrombolytic agents.
Use with caution in presence of known or suspected infection in a catheter because use may release a localized infection into the systemic circulation.
Alteplase does not constitute treatment of underlying deep vein thrombosis; therefore, consider the risk of re-embolism caused by lysis of underlying deep vein thrombi.
Do not administer alteplase if patient is on warfarin and INR is greater than 1.7 or PT is greater than 15 sec; if heparin had been administered within 48 h preceding stroke onset and aPTT was elevated at time of presentation.
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