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Important Safety Information & Indication

Indications

Activase® (alteplase) is indicated for the treatment of acute ischemic stroke. Exclude intracranial hemorrhage as the primary cause of stroke signs and symptoms prior to initiation of treatment. Initiate treatment as soon as possible but within 3 hours after symptom onset.

Activase is indicated for use in acute myocardial infarction (AMI) for the reduction of mortality and reduction of the incidence of heart failure.

Limitation of Use: The risk of stroke may outweigh the benefit produced by thrombolytic therapy in patients whose AMI puts them at low risk for death or heart failure.

Activase is indicated for the lysis of acute massive pulmonary embolism (PE), defined as:

  • Acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments.
  • Acute pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures.

Important Safety Information

Contraindications

Do not administer Activase to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit: current intracranial hemorrhage (ICH); subarachnoid hemorrhage; active internal bleeding; recent (within 3 months) intracranial or intraspinal surgery or serious head trauma; presence of intracranial conditions that may increase the risk of bleeding (e.g., some neoplasms, arteriovenous malformations, or aneurysms); bleeding diathesis; and current severe uncontrolled hypertension.

Do not administer Activase to treat acute myocardial infarction or pulmonary embolism in the following situations in which the risk of bleeding is greater than the potential benefit: active internal bleeding; history of recent stroke; recent (within 3 months) intracranial or intraspinal surgery or serious head trauma; presence of intracranial conditions that may increase the risk of bleeding; bleeding diathesis; and current severe uncontrolled hypertension.

Warnings and Precautions

Bleeding

Activase can cause significant, sometimes fatal internal or external bleeding, especially at arterial and venous puncture sites. Avoid intramuscular injections and trauma to the patient. Perform venipunctures carefully and only as required. Fatal cases of hemorrhage associated with traumatic intubation in patients administered Activase have been reported. Aspirin and heparin have been administered concomitantly with and following infusion with Activase in the management of acute myocardial infarction and pulmonary embolism. The concomitant administration of heparin and aspirin with and following infusions of Activase for the treatment of acute ischemic stroke during the first 24 hours after symptom onset has not been investigated. Because heparin, aspirin, or Activase may cause bleeding complications, carefully monitor for bleeding, especially at arterial puncture sites. Hemorrhage can occur 1 or more days after administration of Activase, while patients are still receiving anticoagulant therapy. If serious bleeding occurs, terminate the Activase infusion, and treat appropriately.

In the following conditions, the risks of bleeding with Activase are increased and should be weighed against the anticipated benefits: recent major surgery or procedure; cerebrovascular disease; recent intracranial hemorrhage; recent gastrointestinal or genitourinary bleeding; recent trauma; hypertension; acute pericarditis; subacute bacterial endocarditis; hemostatic defects including those secondary to severe hepatic or renal disease; significant hepatic dysfunction; pregnancy; diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions; septic thrombophlebitis or occluded AV cannula at seriously infected site; advanced age; and patients currently receiving oral anticoagulants, or any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.

Hypersensitivity

Hypersensitivity, including urticarial / anaphylactic reactions, have been reported after administration of Activase. Rare fatal outcome for hypersensitivity was reported. Angioedema has been observed during and up to 2 hours after Activase infusion in patients treated for acute ischemic stroke and acute myocardial infarction. In many cases, patients received concomitant angiotensin-converting enzyme inhibitors. Monitor patients treated with Activase during and for several hours after infusion for hypersensitivity. If signs of hypersensitivity occur, e.g. anaphylactoid reaction or angioedema develops, discontinue the Activase infusion and promptly institute appropriate therapy (e.g., antihistamines, intravenous corticosteroids, epinephrine).

Thromboembolism

The use of thrombolytics can increase the risk of thrombo-embolic events in patients with high likelihood of left heart thrombus, such as patients with mitral stenosis or atrial fibrillation. Activase has not been shown to treat adequately underlying deep vein thrombosis in patients with PE. Consider the possible risk of re-embolization due to the lysis of underlying deep venous thrombi in this setting.

Cholesterol Embolization

Cholesterol embolism, sometimes fatal, has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown. It is associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.

Coagulation Tests May be Unreliable during Activase Therapy

Coagulation tests and/or measures of fibrinolytic activity may be unreliable during Activase therapy unless specific precautions are taken to prevent in vitro artifacts. When present in blood at pharmacologic concentrations, Activase remains active under in vitro conditions, which can result in degradation of fibrinogen in blood samples removed for analysis.

Adverse Reactions

The most frequent adverse reaction associated with Activase therapy is bleeding.

Please see the full Prescribing Information for additional Important Safety Information and Instructions for Use.

    • National Institute of Neurological Disorders and Stroke. Know stroke. Know the signs. Act in time. National Institute of Neurological Disorders and Stroke website. http://www.ninds.nih.gov/disorders/stroke/knowstroke.htm. Last modified March 29, 2016. Accessed August 12, 2016. 

      National Institute of Neurological Disorders and Stroke. Know stroke. Know the signs. Act in time. National Institute of Neurological Disorders and Stroke website. http://www.ninds.nih.gov/disorders/stroke/knowstroke.htm. Last modified March 29, 2016. Accessed August 12, 2016. 

    • Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50:e344-e418.

      Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50:e344-e418.

    • Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581-641.

      Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016;47(2):581-641.

    • Ferbert A, Brückmann H, Drummen R. Clinical features of proven basilar artery occlusion. Stroke. 1990;21(8):1135-1142. doi:10.1161/01.str.21.8.1135

      Ferbert A, Brückmann H, Drummen R. Clinical features of proven basilar artery occlusion. Stroke. 1990;21(8):1135-1142. doi:10.1161/01.str.21.8.1135

    • Kattah JC, Talkad AV, Wang DZ, et al. HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke. 2009;40(11):3504-10.

      Kattah JC, Talkad AV, Wang DZ, et al. HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke. 2009;40(11):3504-10.

    • Activase [prescribing information]. South San Francisco, CA: Genentech, Inc.

      Activase [prescribing information]. South San Francisco, CA: Genentech, Inc.

    • Arch AE, Weisman DC, Coca S, et al. Missed ischemic stroke diagnosis in the emergency department by emergency medicine and neurology services. Stroke. 2016;47(3):668-73.

      Arch AE, Weisman DC, Coca S, et al. Missed ischemic stroke diagnosis in the emergency department by emergency medicine and neurology services. Stroke. 2016;47(3):668-73.

    • Madsen TE, Khoury J, Cadena R, et al. Potentially missed diagnosis of ischemic stroke in the emergency department in the Greater Cincinnati/Northern Kentucky stroke study. Academic Emergency Medicine. 2016;23(10):1128-35.

      Madsen TE, Khoury J, Cadena R, et al. Potentially missed diagnosis of ischemic stroke in the emergency department in the Greater Cincinnati/Northern Kentucky stroke study. Academic Emergency Medicine. 2016;23(10):1128-35.

    • Masoud HE, de Havenon A, Castonguay AC et al. 2022 brief practice update on intravenous thrombolysis before thrombectomy in patients with large vessel occlusion acute ischemic stroke: a statement from Society of Vascular and Interventional Neurology Guidelines and Practice Standards (GAPS) committee. Stroke Vasc Interv Neurol. 2022;2:e000276. doi:10.1161/SVIN.121.000276

      Masoud HE, de Havenon A, Castonguay AC et al. 2022 brief practice update on intravenous thrombolysis before thrombectomy in patients with large vessel occlusion acute ischemic stroke: a statement from Society of Vascular and Interventional Neurology Guidelines and Practice Standards (GAPS) committee. Stroke Vasc Interv Neurol. 2022;2:e000276. doi:10.1161/SVIN.121.000276

    • Trevo EDFU. Fremont, CA: Stryker International; 2016.

      Trevo EDFU. Fremont, CA: Stryker International; 2016.

    • Solitaire Revascularization Device. Medtronic website. Updated February 2018. Accessed May 9, 2018. http://www.medtronic.com/us-en/healthcare-professionals/products/neurological/revascularization-stroke/solitaire.html

      Solitaire Revascularization Device. Medtronic website. Updated February 2018. Accessed May 9, 2018. http://www.medtronic.com/us-en/healthcare-professionals/products/neurological/revascularization-stroke/solitaire.html

    • Food and Drug Administration. FDA information on medication errors involving Activase and TNKase. September 2015. Available at http://www.fda.gov. Accessed on February 24, 2023.

      Food and Drug Administration. FDA information on medication errors involving Activase and TNKase. September 2015. Available at http://www.fda.gov. Accessed on February 24, 2023.

    • Data on file. Genentech USA. No Title.

      Data on file. Genentech USA. No Title.

    • National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581-1587.

      National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581-1587.

    • FDA Access Summary basis of approval. https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/altegen061896s.pdf. Accessed August 14, 2017.

      FDA Access Summary basis of approval. https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/altegen061896s.pdf. Accessed August 14, 2017.

    • Summers D, Leonard A, Wentworth D, et al. Comprehensive overview of nursing and interdisciplinary care of the acute ischemic stroke patient: a scientific statement from the American Heart Association. Stroke. 2009;40:2911-2944.

      Summers D, Leonard A, Wentworth D, et al. Comprehensive overview of nursing and interdisciplinary care of the acute ischemic stroke patient: a scientific statement from the American Heart Association. Stroke. 2009;40:2911-2944.

    • American Association of Neuroscience Nurses. Reference Series for Clinical Practice. 2004. Available at https://aann.org/. Accessed on February 23, 2023.

      American Association of Neuroscience Nurses. Reference Series for Clinical Practice. 2004. Available at https://aann.org/. Accessed on February 23, 2023.

    • Tamm A, Siddiqui M, Shuaib A, et al. Impact of stroke care unit on patient outcomes in a community hospital. Stroke. 2014;45(1):211-216.

      Tamm A, Siddiqui M, Shuaib A, et al. Impact of stroke care unit on patient outcomes in a community hospital. Stroke. 2014;45(1):211-216.

    • CMS Quality Measurement Programs Characteristics. Centers for Medicare and Medicaid Services website. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/QualityMeasures/Downloads/CMSQualityMeasurementProgramsCharacteristics.PDF. Published June 28, 2012. Accessed August 13, 2016.

      CMS Quality Measurement Programs Characteristics. Centers for Medicare and Medicaid Services website. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/QualityMeasures/Downloads/CMSQualityMeasurementProgramsCharacteristics.PDF. Published June 28, 2012. Accessed August 13, 2016.

    • The Joint Commission, Stroke. Last updated June 17, 2016. Accessed August 1, 2016. https://www.jointcommission.org/stroke/

      The Joint Commission, Stroke. Last updated June 17, 2016. Accessed August 1, 2016. https://www.jointcommission.org/stroke/

    • Skolarus LE, Meurer WJ, Shanmugasundaram K, et al. Marked regional variation in acute stroke treatment among Medicare beneficiaries. Stroke. 2015;46:1890-1896.

      Skolarus LE, Meurer WJ, Shanmugasundaram K, et al. Marked regional variation in acute stroke treatment among Medicare beneficiaries. Stroke. 2015;46:1890-1896.

    • ICD-10. https://www.cms.gov/Medicare/Coding/ICD10/. Accessed August 14, 2017. 

      ICD-10. https://www.cms.gov/Medicare/Coding/ICD10/. Accessed August 14, 2017. 

    • Schwamm LH, Pancioli A, Acker JE, et al. Recommendations for the establishment of stroke systems of care: recommendations from the American Stroke Association’s Task Force on the Development of Stroke Systems. Stroke. 2005;36(3):690-703.

      Schwamm LH, Pancioli A, Acker JE, et al. Recommendations for the establishment of stroke systems of care: recommendations from the American Stroke Association’s Task Force on the Development of Stroke Systems. Stroke. 2005;36(3):690-703.

    • Fonarow GC, Smith EE, Saver JL, et al. Improving door-to-needle times in acute ischemic stroke: the design and rationale for the American Heart Association/American Stroke Association's Target: Stroke initiative. Stroke. 2011;42(10):2983-2989.

      Fonarow GC, Smith EE, Saver JL, et al. Improving door-to-needle times in acute ischemic stroke: the design and rationale for the American Heart Association/American Stroke Association's Target: Stroke initiative. Stroke. 2011;42(10):2983-2989.

    • Goyal M, Menon BK, Hill MD, Demchuk A. Consistently achieving computed tomography to endovascular recanalization <90 minutes: solutions and innovations. Stroke. 2014;45(12):e252-e256.

      Goyal M, Menon BK, Hill MD, Demchuk A. Consistently achieving computed tomography to endovascular recanalization <90 minutes: solutions and innovations. Stroke. 2014;45(12):e252-e256.

    • Kalanithi L, Tai W, Conley J, Platchek T, Zulman D, Milstein A. Better health, less spending: delivery innovation for ischemic cerebrovascular disease. Stroke. 2014;45(10):3105-3111.

      Kalanithi L, Tai W, Conley J, Platchek T, Zulman D, Milstein A. Better health, less spending: delivery innovation for ischemic cerebrovascular disease. Stroke. 2014;45(10):3105-3111.

    • Meretoja A, Weir L, Ugalde M, et al. Helsinki model cut stroke thrombolysis delays to 25 minutes in Melbourne in only 4 months. Neurology. 2013;81(12):1071-1076.

      Meretoja A, Weir L, Ugalde M, et al. Helsinki model cut stroke thrombolysis delays to 25 minutes in Melbourne in only 4 months. Neurology. 2013;81(12):1071-1076.

    • Nguyen-Huynh MN. KPNC stroke EXPRESS: expediting the process of evaluating and stopping stroke. Presentation; 2016.

      Nguyen-Huynh MN. KPNC stroke EXPRESS: expediting the process of evaluating and stopping stroke. Presentation; 2016.

    • American Heart Association. Target: Stroke. Accessed April 10, 2023. https://www.heart.org/en/professional/quality-improvement/target-stroke  

      American Heart Association. Target: Stroke. Accessed April 10, 2023. https://www.heart.org/en/professional/quality-improvement/target-stroke  

    • Wechsler LR, Demaerschalk BM, Schwamm LH, et al. Telemedicine quality and outcomes in stroke: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2017 Jan 1;48(1):e3-25.

      Wechsler LR, Demaerschalk BM, Schwamm LH, et al. Telemedicine quality and outcomes in stroke: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2017 Jan 1;48(1):e3-25.

    • American Hospital Association. http://www.aha.org/research/reports/tw/12oct-tw-quality.pdf. October 2012. Accessed October 11, 2016.

      American Hospital Association. http://www.aha.org/research/reports/tw/12oct-tw-quality.pdf. October 2012. Accessed October 11, 2016.

    • Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352.

      Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352.

    • Fesmire FM, Brown MD, Espinosa JA, et al. Critical issues in the evaluation and management of adult patients presenting to the emergency department with suspected pulmonary embolism. Ann Emerg Med. 2011 Jun;57(6):628-652.e75.

      Fesmire FM, Brown MD, Espinosa JA, et al. Critical issues in the evaluation and management of adult patients presenting to the emergency department with suspected pulmonary embolism. Ann Emerg Med. 2011 Jun;57(6):628-652.e75.

    • Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest. 2002;121:877-905.

      Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest. 2002;121:877-905.

    • Tan KT, Oudkerk M, van Beek EJR. Deep Vein Thrombosis and Pulmonary Embolism. In: Hallet JW Jr, Mills JL, Earnshaw JJ, Reekers JA, eds. Comprehensive Vascular and Endovascular Surgery. Philadelphia, PA: Elsevier Limited; 2003.

      Tan KT, Oudkerk M, van Beek EJR. Deep Vein Thrombosis and Pulmonary Embolism. In: Hallet JW Jr, Mills JL, Earnshaw JJ, Reekers JA, eds. Comprehensive Vascular and Endovascular Surgery. Philadelphia, PA: Elsevier Limited; 2003.

    • Martin-Schild S, Albright KC, Tanksley J, et al. Zero on the NIHSS does not equal the absence of stroke. Ann Emerg Med. 2011;57:42-45.

      Martin-Schild S, Albright KC, Tanksley J, et al. Zero on the NIHSS does not equal the absence of stroke. Ann Emerg Med. 2011;57:42-45.

    • NIH Stroke Scale International. Approach to Human Subject Protection and Patient Safety. Available at: http://www.nihstrokescale.org. Accessed March 18, 2020.

      NIH Stroke Scale International. Approach to Human Subject Protection and Patient Safety. Available at: http://www.nihstrokescale.org. Accessed March 18, 2020.

    • Centers for Disease Control and Prevention. MMWR. 2009 May 1;58:421-426.

      Centers for Disease Control and Prevention. MMWR. 2009 May 1;58:421-426.

    • Menon BK, Saver JL, Prabhakaran S, et al. Risk score for intracranial hemorrhage in patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Stroke. 2012;43:2293-2299.

      Menon BK, Saver JL, Prabhakaran S, et al. Risk score for intracranial hemorrhage in patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Stroke. 2012;43:2293-2299.

    • Searls DE, Pazdera L, Korbel E, Vysata O, Caplan LR. Symptoms and signs of posterior circulation ischemia in the New England Medical Center posterior circulation registry. Arch Neurol. 2012;69(3):346-351. doi:10.1001/archneurol.2011.2083

      Searls DE, Pazdera L, Korbel E, Vysata O, Caplan LR. Symptoms and signs of posterior circulation ischemia in the New England Medical Center posterior circulation registry. Arch Neurol. 2012;69(3):346-351. doi:10.1001/archneurol.2011.2083