Drug: Activase

Activase® (Alteplase) is a tissue plasminogen activator produced by recombinant DNA technology. It is a sterile, purified glycoprotein of 527 amino acids. It is synthesized using the complementary DNA (cDNA) for natural human tissue-type plasminogen activator obtained from a human melanoma cell line. The manufacturing process involves the secretion of the enzyme alteplase into the culture medium by an established mammalian cell line (Chinese Hamster Ovary cells) into which the cDNA for alteplase has been genetically inserted. Fermentation is carried out in a nutrient medium containing the antibiotic gentamicin, 100 mg/L. However, the presence of the antibiotic is not detectable in the final product. Phosphoric acid and/or sodium hydroxide may be used prior to lyophilization for pH adjustment. Activase (alteplase) is a sterile, white to off-white, lyophilized powder for intravenous administration after reconstitution with Sterile Water for Injection, USP. Quantitative Composition of the Lyophilized Product   100 mg Vial 50 mg Vial Alteplase 100 mg (58 million IU) 50 mg (29 million IU) L-Arginine 3.5 g 1.7 g Phosphoric Acid 1 g 0.5 g Polysorbate 80 ≤ 11 mg ≤ 4 mg Vacuum No Yes Biological potency is determined by an in vitro clot lysis assay and is expressed in International Units as tested against the WHO standard. The specific activity of Activase (alteplase) is 580,000 IU/mg. Last reviewed on RxList: 5/9/2008
This monograph has been modified to include the generic and brand name in many instances.

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Bleeding The most frequent adverse reaction associated with Activase (alteplase) in all approved indications is bleeding (see WARNINGS).15,16 Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, Activase (alteplase) therapy should be discontinued immediately, along with any concomitant therapy with heparin. Death and permanent disability are not uncommonly reported in patients that have experienced stroke (including intracranial bleeding) and other serious bleeding episodes. In the GUSTO trial for the treatment of acute myocardial infarction, using the accelerated infusion regimen the incidence of all strokes for the Activase (alteplase) treated patients was 1.6%, while the incidence of nonfatal stroke was 0.9%. The incidence of hemorrhagic stroke was 0.7%, not all of which were fatal. The incidence of all strokes, as well as that for hemorrhagic stroke, increased with increasing age (see CLINICAL PHARMACOLOGY: Accelerated Infusion in AMI Patients). Data from previous trials utilizing a 3 hour infusion of < 100 mg indicated that the incidence of total stroke in six randomized double blind placebo-controlled trials2,7-11,17 was 1.2% (37/3161) in Alteplase treated patients compared with 0.9% (27/3092) in placebo- treated patients. For the 3-hour infusion regimen, the incidence of significant internal bleeding (estimated as > 250 cc blood loss) has been reported in studies in over 800 patients. These data do not include patients treated with the Alteplase accelerated infusion.   Total Dose ≤ 100 mg gastrointestinal 5% genitourinary 4% ecchymosis 1% retroperitoneal < 1% epistaxis < 1% gingival < 1% The incidence of intracranial hemorrhage (ICH) in acute myocardial infarction patients treated with Activase (alteplase) is as follows: Dose Number of Patients ICH (%) 100 mg, 3-hour 3272 0.4 ≤ 100 mg, accelerated 10,396 0.7 150 mg 1779 1.3 1-1.4 mg/kg 237 0.4 These data indicate that a dose of 150 mg of Activase (alteplase) should not be used in the treatment of AMI because it has been associated with an increase in intracranial bleeding.18 For acute massive pulmonary embolism, bleeding events were consistent with the general safety profile observed with Activase (alteplase) in acute myocardial infarction patients receiving the 3-hour infusion regimen. The incidence of ICH, especially symptomatic ICH, in patients with acute ischemic stroke was higher in Activase (alteplase) -treated patients than placebo patients (see CLINICAL PHARMACOLOGY). A study of another alteplase product, Actilyse, in acute ischemic stroke, suggested that doses greater than 0.9 mg/kg may be associated with an increased incidence of ICH.19 Doses greater than 0.9 mg/kg (maximum 90 mg) should not be used in the management of acute ischemic stroke. Bleeding events other than ICH were noted in the studies of acute ischemic stroke and were consistent with the general safety profile of Activase (alteplase) . In The NINDS t-PA Stroke Trial (Parts 1 and 2), the frequency of bleeding requiring red blood cell transfusions was 6.4% for Activase (alteplase) -treated patients compared to 3.8% for placebo (p=0.19, using Mantel-Haenszel Chi-Square). Fibrin which is part of the hemostatic plug formed at needle puncture sites will be lysed during Activase (alteplase) therapy. Therefore, Activase (alteplase) therapy requires careful attention to potential bleeding sites, e.g., catheter insertion sites, and arterial puncture sites. Allergic Reactions Allergic-type reactions, e.g., anaphylactoid reaction, laryngeal edema, orolingual angioedema, rash, and urticaria have been reported. A cause and effect relationship to Activase (alteplase) therapy has not been established. When such reactions occur, they usually respond to conventional therapy. There have been post-marketing reports of orolingual angioedema associated with the use of Activase (alteplase) . Most reports were of patients treated for acute ischemic stroke, some reports were of patients treated for acute myocardial infarctions (see PRECAUTIONS: General). Many of these patients received concomitant angiotensin-converting enzyme inhibitors (see PRECAUTIONS: DRUG INTERACTIONS). Most cases resolved with prompt treatment; there have been rare fatalities as a result of upper airway hemorrhage from intubation trauma. Other Adverse Reactions The following adverse reactions have been reported among patients receiving Activase (alteplase) in clinical trials and in post-marketing experience. These reactions are frequent sequelae of the underlying disease and the effect of Activase (alteplase) on the incidence of these events is unknown. Use in Acute Myocardial Infarction: Arrhythmias, 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. These events may be life threatening and may lead to death. Nausea and/or vomiting, hypotension and fever have also been reported. Use in Pulmonary Embolism: Pulmonary reembolization, pulmonary edema, pleural effusion, thromboembolism, hypotension. These events may be life threatening and may lead to death. Fever has also been reported. Use in Acute Ischemic Stroke: Cerebral edema, cerebral herniation, seizure, new ischemic stroke. These events may be life threatening and may lead to death. Read the Activase (alteplase) Side Effects Center for a complete guide to possible side effectsLearn More »

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Activase® (Alteplase) is for intravenous administration only. Extravasation of Activase (alteplase) infusion can cause ecchymosis and/or inflammation. Management consists of terminating the infusion at that IV site and application of local therapy. Acute Myocardial Infarction Administer Activase (alteplase) as soon as possible after the onset of symptoms. There are two Activase (alteplase) dose regimens for use in the management of acute myocardial infarction; controlled studies to compare clinical outcomes with these regimens have not been conducted. A DOSE OF 150 mg OF ACTIVASE (alteplase) SHOULD NOT BE USED FOR THE TREATMENT OF ACUTE MYOCARDIAL INFARCTION BECAUSE IT HAS BEEN ASSOCIATED WITH AN INCREASE IN INTRACRANIAL BLEEDING. Accelerated Infusion The recommended total dose is based upon patient weight, not to exceed 100 mg. For patients weighing > 67 kg, the recommended dose administered is 100 mg as a 15 mg intravenous bolus, followed by 50 mg infused over the next 30 minutes, and then 35 mg infused over the next 60 minutes. For patients weighing ≤ 67 kg, the recommended dose is administered as a 15 mg intravenous bolus, followed by 0.75 mg/kg infused over the next 30 minutes not to exceed 50 mg, and then 0.50 mg/kg over the next 60 minutes not to exceed 35 mg. The safety and efficacy of this accelerated infusion of Alteplase regimen has only been investigated with concomitant administration of heparin and aspirin as described in CLINICAL PHARMACOLOGY.
  1. The bolus dose may be prepared in one of the following ways:
    1. By removing 15 mL from the vial of reconstituted (1 mg/mL) Activase (alteplase) using a syringe and needle. If this method is used with the 50 mg vials, the syringe should not be primed with air and the needle should be inserted into the Activase (alteplase) vial stopper. If the 100 mg vial is used, the needle should be inserted away from the puncture mark made by the transfer device.
    2. By removing 15 mL from a port (second injection site) on the infusion line after the infusion set is primed.
    3. By programming an infusion pump to deliver a 15 mL (1 mg/mL) bolus at the initiation of the infusion.
  2. The remainder of the Activase (alteplase) dose may be administered as follows:
50 mg vials-administer using either a polyvinyl chloride bag or glass vial and infusion set. 100 mg vial-insert the spike end of an infusion set through the same puncture site created by the transfer device in the stopper of the vial of reconstituted Activase (alteplase) . Hang the Activase (alteplase) vial from the plastic molded capping attached to the bottom of the vial. 3-Hour Infusion The recommended dose is 100 mg administered as 60 mg in the first hour (of which 6 to 10 mg is administered as a bolus), 20 mg over the second hour, and 20 mg over the third hour. For smaller patients ( < 65 kg), a dose of 1.25 mg/kg administered over 3 hours, as described above, may be used.15 Although the value of the use of anticoagulants during and following administration of Activase (alteplase) has not been fully studied, heparin has been administered concomitantly for 24 hours or longer in more than 90% of patients. Aspirin and/or dipyridamole have been given to patients receiving Alteplase during and/or following heparin treatment.
  1.  The bolus dose may be prepared in one of the following ways:
    1. By removing 6 to 10 mL from the vial of reconstituted (1 mg/mL) Activase (alteplase) using a syringe and needle. If this method is used with the 50 mg vials, the syringe should not be primed with air and the needle should be inserted into the Activase (alteplase) vial stopper. If the 100 mg vial is used, the needle should be inserted away from the puncture mark made by the transfer device.
    2. By removing 6 to 10 mL from a port (second injection site) on the infusion line after the infusion set is primed.
    3. By programming an infusion pump to deliver a 6 to 10 mL (1 mg/mL) bolus at the initiation of the infusion.
  2.   The remainder of the Activase (alteplase) dose may be administered as follows:
50 mg vials-administer using either a polyvinyl chloride bag or glass vial and infusion set. 100 mg vial-insert the spike end of an infusion set through the same puncture site created by the transfer device in the stopper of the vial of reconstituted Activase (alteplase) . Hang the Activase (alteplase) vial from the plastic molded capping attached to the bottom of the vial. Acute Ischemic Stroke THE TOTAL DOSE FOR TREATMENT OF ACUTE ISCHEMIC STROKE SHOULD NOT EXCEED 90 mg. The recommended dose is 0.9 mg/kg (not to exceed 90 mg total dose) infused over 60 minutes with 10% of the total dose administered as an initial intravenous bolus over 1 minute. The safety and efficacy of this regimen with concomitant administration of heparin and aspirin during the first 24 hours after symptom onset has not been investigated.
  1. The bolus dose may be prepared in one of the following ways:
    1. By removing the appropriate volume from the vial of reconstituted (1 mg/mL) Activase (alteplase) using a syringe and needle. If this method is used with the 50 mg vials, the syringe should not be primed with air and the needle should be inserted into the Activase (alteplase) vial stopper. If the 100 mg vial is used, the needle should be inserted away from the puncture mark made by the transfer device.
    2. By removing the appropriate volume from a port (second injection site) on the infusion line after the infusion set is primed.
    3. By programming an infusion pump to deliver the appropriate volume as a bolus at the initiation of the infusion.
  2. The remainder of the Activase (alteplase) dose may be administered as follows:
50 mg vials-administer using either a polyvinyl chloride bag or glass vial and infusion set. 100 mg vial-remove from the vial any quantity of drug in excess of that specified for patient treatment. Insert the spike end of an infusion set through the same puncture site created by the transfer device in the stopper of the vial of reconstituted Activase (alteplase) . Hang the Activase (alteplase) vial from the plastic molded capping attached to the bottom of the vial. Pulmonary Embolism The recommended dose is 100 mg administered by intravenous infusion over 2 hours. Heparin therapy should be instituted or reinstituted near the end of or immediately following the Activase (alteplase) infusion when the partial thromboplastin time or thrombin time returns to twice normal or less. The Activase (alteplase) dose may be administered as follows: 50 mg vials-administer using either a polyvinyl chloride bag or glass vial and infusion set. 100 mg vial-insert the spike end of an infusion set through the same puncture site created by the transfer device in the stopper of the vial of reconstituted Activase (alteplase) . Hang the Activase (alteplase) vial from the plastic molded capping attached to the bottom of the vial. Reconstitution and Dilution Activase (alteplase) should be reconstituted by aseptically adding the appropriate volume of the accompanying Sterile Water for Injection, USP, to the vial. It is important that Activase (alteplase) be reconstituted only with Sterile Water for Injection, USP, without preservatives. Do not use Bacteriostatic Water for Injection, USP. The reconstituted preparation results in a colorless to pale yellow transparent solution containing Activase (alteplase) 1mg/mL at approximately pH 7.3. The osmolality of this solution is approximately 215 mOsm/kg. Because Activase (alteplase) contains no antibacterial preservatives, it should be reconstituted immediately before use. The solution may be used for intravenous administration within 8 hours following reconstitution when stored between 2-30oC (36-86oF). Before further dilution or administration, the product should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit. Activase (alteplase) may be administered as reconstituted at 1 mg/mL. As an alternative, the reconstituted solution may be diluted further immediately before administration in an equal volume of 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, to yield a concentration of 0.5 mg/mL. Either polyvinyl chloride bags or glass vials are acceptable. Activase (alteplase) is stable for up to 8 hours in these solutions at room temperature. Exposure to light has no effect on the stability of these solutions. Excessive agitation during dilution should be avoided; mixing should be accomplished with gentle swirling and/or slow inversion. Do not use other infusion solutions, e.g., Sterile Water for Injection, USP, or preservative- containing solutions for further dilution. 50 mg Vials Reconstitution should be carried out using a large bore needle (e.g., 18 gauge) and a syringe, directing the stream of Sterile Water for Injection, USP, into the lyophilized cake. DO NOT USE IF VACUUM IS NOT PRESENT. Slight foaming upon reconstitution is not unusual; standing undisturbed for several minutes is usually sufficient to allow dissipation of any large bubbles. No other medication should be added to infusion solutions containing Activase (alteplase) . Any unused infusion solution should be discarded. 100 mg Vial Reconstitution should be carried out using the transfer device provided, adding the contents of the accompanying 100 mL vial of Sterile Water for Injection, USP, to the contents of the 100 mg vial of Activase (alteplase) powder. Slight foaming upon reconstitution is not unusual; standing undisturbed for several minutes is usually sufficient to allow dissipation of any large bubbles. Please refer to the accompanying Instructions for Reconstitution and Administration. 100 mg VIALS DO NOT CONTAIN VACUUM. 100 mg VIAL RECONSTITUTION
  1.  Use aseptic technique throughout.
  2.  Remove the protective flip-caps from one vial of Activase (alteplase) and one vial of Sterile Water for Injection, USP (SWFI).
  3.  Open the package containing the transfer device by peeling the paper label off the package.
  4.  Remove the protective cap from one end of the transfer device and keeping the vial of SWFI upright, insert the piercing pin vertically into the center of the stopper of the vial of SWFI.
  5.  Remove the protective cap from the other end of the transfer device. DO NOT INVERT THE VIAL OF SWFI.
  6.  Holding the vial of Activase (alteplase) upside-down, position it so that the center of the stopper is directly over the exposed piercing pin of the transfer device.
  7.  Push the vial of Activase (alteplase) down so that the piercing pin is inserted through the center of the Activase (alteplase) vial stopper.
  8.  Invert the two vials so that the vial of Activase (alteplase) is on the bottom (upright) and the vial of SWFI is upside-down, allowing the SWFI to flow down through the transfer device. Allow the entire contents of the vial of SWFI to flow into the Activase (alteplase) vial (approximately 0.5 cc of SWFI will remain in the diluent vial). Approximately 2 minutes are required for this procedure.
  9.  Remove the transfer device and the empty SWFI vial from the Activase (alteplase) vial. Safely discard both the transfer device and the empty diluent vial according to institutional procedures.
  10. Swirl gently to dissolve the Activase (alteplase) powder. DO NOT SHAKE.
No other medication should be added to infusion solutions containing Activase (alteplase) . Any unused infusion solution should be discarded.

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The interaction of Activase (alteplase) with other cardioactive or cerebroactive drugs has not been studied. In addition to bleeding associated with heparin and vitamin K antagonists, drugs that alter platelet function (such as acetylsalicylic acid, dipyridamole and Abciximab) may increase the risk of bleeding if administered prior to, during, or after Activase (alteplase) therapy. There have been post-marketing reports of orolingual angioedema associated with the use of Activase (alteplase) . Many patients, primarily acute ischemic stroke patients, were receiving concomitant Angiotensin-converting enzyme inhibitors. (See PRECAUTIONS: General and ADVERSE REACTIONS: Allergic Reactions). Use of Antithrombotics Aspirin and heparin have been administered concomitantly with and following infusions of Activase (alteplase) in the management of acute myocardial infarction or pulmonary embolism. Because heparin, aspirin, or Activase (alteplase) may cause bleeding complications, careful monitoring for bleeding is advised, especially at arterial puncture sites. The concomitant use of heparin or aspirin during the first 24 hours following symptom onset were prohibited in The NINDS t-PA Stroke Trial. The safety of such concomitant use with Activase (alteplase) for the management of acute ischemic stroke is unknown. Blood Pressure Control Blood pressure should be monitored frequently and controlled during and following Activase (alteplase) administration in the management of acute ischemic stroke. In The NINDS t-PA Stroke Trial, blood pressure was actively controlled ( ≤ 185/110 mm Hg) for 24 hours. Blood pressure was monitored during the hospital stay. REFERENCES 2.   Topol EJ, Morriss DC, Smalling RW, et al. A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue type plasminogen activator (Activase® (alteplase) ) in acute myocardial infarction. J Am Coll Cardiol. 1987;9:1205-13. 7.   Guerci AD, Gerstenblith G, Brinker JA, et al. A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty. New Engl J Med. 1987;317:1613-18. 8.   O'Rourke M, Baron D, Keogh A, et al. Limitation of myocardial infarction by early infusion of recombinant tissue plasminogen activator. Circulation. 1988;77:1311-15. 11. Van de Werf F, Arnold AER, et al. Effect of intravenous tissue-plasminogen activator on infarct size, left ventricular function and survival in patients with acute myocardial infarction. Br Med J. 1988;297:1374-9. 15. Califf RM, Topol EJ, George BS, et al. Hemorrhagic complications associated with the use of intravenous tissue plasminogen activator in treatment of acute myocardial infarction. Am J Med. 1988;85:353-9. 16.  Bovill EG, Terrin ML, Stump DC, et al. Hemorrhagic events during therapy with recombinant tissue type plasminogen activator, heparin, and aspirin for acute myocardial infarction: results from the thrombolysis in myocardial infarction (TIMI), Phase II trial. Ann Int Med. 1991;115(4):256-65. 17. National Heart Foundation of Australia Coronary Thrombolysis Group. Coronary thrombolysis and myocardial infarction salvage by tissue plasminogen activator given up to 4 hours after onset of myocardial infarction. Lancet. 1988;1:203-7. 18. Gore JM, Sloan M, Price TR, et al. and the TIMI Investigators. Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the thrombolysis in myocardial infarction study. Circulation. 1991;83:448-59. 19.  Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. for the ECASS Study Group. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995;274:1017-25. Read the Activase Drug Interactions Center for a complete guide to possible interactions Learn More »

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Acute Myocardial Infarction Activase (alteplase) ® (Alteplase) is indicated for use in the management of acute myocardial infarction in adults for the improvement of ventricular function following AMI, the reduction of the incidence of congestive heart failure, and the reduction of mortality associated with AMI. Treatment should be initiated as soon as possible after the onset of AMI symptoms (see CLINICAL PHARMACOLOGY). Acute Ischemic Stroke Activase® (Alteplase) is indicated for the management of acute ischemic stroke in adults for improving neurological recovery and reducing the incidence of disability. Treatment should only be initiated within 3 hours after the onset of stroke symptoms, and after exclusion of intracranial hemorrhage by a cranial computerized tomography (CT) scan or other diagnostic imaging method sensitive for the presence of hemorrhage (see CONTRAINDICATIONS). Pulmonary Embolism Activase® (Alteplase) is indicated in the management of acute massive pulmonary embolism (PE) in adults: -For the lysis of acute pulmonary emboli, defined as obstruction of blood flow to a lobe or multiple segments of the lungs.
-For the lysis of pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures. The diagnosis should be confirmed by objective means, such as pulmonary angiography or noninvasive procedures such as lung scanning.

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Acute Myocardial Infarction or Pulmonary Embolism Activase (alteplase) therapy in patients with acute myocardial infarction or pulmonary embolism is contraindicated in the following situations because of an increased risk of bleeding:
  •    Active internal bleeding
  •     History of cerebrovascular accident
  •     Recent intracranial or intraspinal surgery or trauma (see WARNINGS)
  •     Intracranial neoplasm, arteriovenous malformation, or aneurysm
  •     Known bleeding diathesis
  •     Severe uncontrolled hypertension
Acute Ischemic Stroke Activase (alteplase) therapy in patients with acute ischemic stroke is contraindicated in the following situations because of an increased risk of bleeding, which could result in significant disability or death:
  •     Evidence of intracranial hemorrhage on pretreatment evaluation
  •     Suspicion of subarachnoid hemorrhage on pretreatment evaluation
  •     Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke
  •     History of intracranial hemorrhage
  •     Uncontrolled hypertension at time of treatment (e.g., > 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 oral anticoagulants (e.g., warfarin sodium) or an International Normalized Ratio (INR) > 1.7 or a prothrombin time (PT) > 15 seconds
- Administration of heparin within 48 hours preceding the onset of stroke and have an elevated activated partial thromboplastin time (aPTT) at presentation
-  Platelet count < 100,000/mm3 REFERENCES 14. Aylward P, Wilcox R, Horgan J, White H, Granger C, Califf R, et al. for the GUSTO-I Investigators. Relation of increased arterial blood pressure to mortality and stroke in the context of contemporary thrombolytic therapy for acute myocardial infarction: a randomized trial. Ann Int Med. 1996;125:891-900. Last reviewed on RxList: 5/9/2008
This monograph has been modified to include the generic and brand name in many instances.

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No information provided.

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Activase® (Alteplase), is supplied as a sterile, lyophilized powder in 50 mg vials containing vacuum and in 100 mg vials without vacuum. Each 50 mg Activase (alteplase) vial (29 million IU) is packaged with diluent for reconstitution
(50 mL Sterile Water for Injection, USP): NDC 50242-044-13. Each 100 mg Activase (alteplase) vial (58 million IU) is packaged with diluent for reconstitution
(100 mL Sterile Water for Injection, USP), and one transfer device: NDC 50242-085-27. Storage Store lyophilized Activase (alteplase) at controlled room temperature not to exceed 30°C (86°F), or under refrigeration (2-8°C/36-46°F). Protect the lyophilized material during extended storage from excessive exposure to light. Do not use beyond the expiration date stamped on the vial. Manufactured by: GENENTECH, INC. 1 DNA Way, South San Francisco, CA 94080-4990. Revision Date December 2005. FDA Approval Date May 2002. FDA rev date: 1/4/2005  Last reviewed on RxList: 5/9/2008
This monograph has been modified to include the generic and brand name in many instances.

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General Standard management of myocardial infarction or pulmonary embolism should be implemented concomitantly with Activase (alteplase) treatment. Noncompressible arterial puncture must be avoided and internal jugular and subclavian venous punctures should be avoided to minimize bleeding from noncompressible sites. Arterial and venous punctures should be minimized. In the event of serious bleeding, Activase (alteplase) and heparin should be discontinued immediately. Heparin effects can be reversed by protamine. Orolingual angioedema has been observed in post-market experience in patients treated for acute ischemic stroke and in patients treated for acute myocardial infarction (see PRECAUTIONS: DRUG INTERACTIONS and ADVERSE REACTIONS: Allergic Reactions). Onset of angioedema occurred during and up to 2 hours after infusion of Activase (alteplase) . In many cases, patients were receiving concomitant Angiotensin-converting enzyme inhibitors. Patients treated with Activase (alteplase) should be monitored during and for several hours after infusion for signs of orolingual angioedema. If angioedema is noted, promptly institute appropriate therapy (e.g. antihistamines, intravenous corticosteroids or epinephrine) and consider discontinuing the Activase (alteplase) infusion. Rare fatal cases of hemorrhage associated with traumatic intubation in patients administered Activase (alteplase) have been reported. Readministration There is no experience with readministration of Activase (alteplase) . If an anaphylactoid reaction occurs, the infusion should be discontinued immediately and appropriate therapy initiated. Although sustained antibody formation in patients receiving one dose of Activase (alteplase) has not been documented, readministration should be undertaken with caution. Detectable levels of antibody (a single point measurement) were reported in one patient, but subsequent antibody test results were negative. Drug/Laboratory Test Interactions During Activase (alteplase) therapy, if coagulation tests and/or measures of fibrinolytic activity are performed, the results may be unreliable unless specific precautions are taken to prevent in vitro artifacts. Activase (alteplase) is an enzyme that when present in blood in pharmacologic concentrations remains active under in vitro conditions. This can lead to degradation of fibrinogen in blood samples removed for analysis. Collection of blood samples in the presence of aprotinin (150-200 units/mL) can to some extent mitigate this phenomenon. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals have not been performed to evaluate the carcinogenic potential or the effect on fertility. Short-term studies, which evaluated tumorigenicity of Activase (alteplase) and effect on tumor metastases in rodents, were negative. Studies to determine mutagenicity (Ames test) and chromosomal aberration assays in human lymphocytes were negative at all concentrations tested. Cytotoxicity, as reflected by a decrease in mitotic index, was evidenced only after prolonged exposure and only at the highest concentrations tested. Pregnancy (Category C) Activase (alteplase) has been shown to have an embryocidal effect in rabbits when intravenously administered in doses of approximately two times (3 mg/kg) the human dose for AMI. No maternal or fetal toxicity was evident at 0.65 times (1 mg/kg) the human dose in pregnant rats and rabbits dosed during the period of organogenesis. There are no adequate and well controlled studies in pregnant women. Activase (alteplase) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers It is not known whether Activase (alteplase) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Activase (alteplase) is administered to a nursing woman. Pediatric Use Safety and effectiveness of Activase (alteplase) in pediatric patients have not been established.Last reviewed on RxList: 5/9/2008
This monograph has been modified to include the generic and brand name in many instances.

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