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In acute ischemic stroke
Patient selection and protocol adherence is important to stroke outcomes

Activase (t-PA) treatment begins with proper patient selection

Activase is the only FDA-approved medication indicated for the treatment of acute ischemic stroke

Activase 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 image method sensitive for the presence of hemorrhage.

Activase may be contraindicated for certain types of patients

Activase therapy in patients with acute ischemic stroke is contraindicated in the following situations because of an increased risk of bleeding, which would 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 (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 oral anticoagulants (eg, 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 an elevated activated partial thromboplastin time (aPTT) at presentation
    • – Platelet count <100,000/mm3

Select eligibility considerations included in the AHA/ASA 2007 guidelines:

  • Diagnosis of ischemic stroke causing measurable neurologic deficit
  • No gastrointestinal or urinary tract hemorrhage in previous 21 days
  • No major surgery in the previous 14 days
  • No arterial puncture at a noncompressible site in the previous 7 days
  • If receiving heparin in previous 48 hours, aPTT must be in normal range
  • Platelet count ≥100,000/mm3
  • Blood glucose concentration ≥50 mg/dL
  • CT does not show a multilobar infarction (hypodensity >1/3 cerebral hemisphere)

Activase should be used with caution in certain patients

The risks of Activase therapy (eg, increased risk of SICH) to treat acute ischemic stroke may be increased in the conditions listed here. Therefore, in these situations the anticipated benefits should be weighed against the potential risks:

  • Patients with severe neurologic deficit (eg, NIHSS >22) at presentation
  • Patients with major and early infarct signs on a cranial CT scan
  • (eg, substantial edema, mass effect, midline shift)
  • Patients of advanced age (eg, >75 years)

Warnings in special patient populations

Due to the increased risk of misdiagnosis of acute ischemic stroke, special diligence is required in making this diagnosis in patients whose blood glucose values are <50 mg/dL or >400 mg/dL

The safety and efficacy of treatment with Activase in patients with minor neurologic deficit or with rapidly improving symptoms prior to the start of Activase administration have not been evaluated; therefore, treatment is not recommended.

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Indication
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).

Important Safety Information
Activase therapy in patients with AIS is contraindicated in certain situations (eg, suspicion of subarachnoid hemorrhage on pretreatment evaluation, recent (within 3 months) intracranial or intraspinal surgery, history of intracranial hemorrhage, uncontrolled hypertension at time of treatment, active internal bleeding, known bleeding diathesis (eg, current use of oral anticoagulants, administration of heparin within 48 hours of onset of stroke, platelet count <100,000) (see CONTRAINDICATIONS for full list).

The most common complication during Activase therapy is bleeding. Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, Activase therapy should be discontinued immediately. Death and permanent disability are not uncommonly reported in patients who have experienced stroke (including intracranial bleeding) and other serious bleeding episodes.

The risks of Activase therapy may be increased and should be weighed against the anticipated benefits in certain conditions. [See WARNINGS in full prescribing information].

  • Patients with severe neurological deficit (eg, NIHSS >22) at presentation. There is an increased risk of intracranial hemorrhage in these patients.
  • Patients with major early infarct signs on a computerized cranial tomography (CT) scan (eg, substantial edema, mass effect, or midline shift).

Treatment of patients with minor neurological deficit or with rapidly improving symptoms is not recommended.

Orolingual angioedema has been observed in postmarketing experience in patients treated with Activase for AIS. Patients should be monitored during and for several hours after infusion for signs of orolingual angioedema.

Please click here for full prescribing information.
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