MD Conference Express ISC 2013 - (Page 6)

Trim: 7" Brief Summary—Please see the Activase package insert for full prescribing information Powder for reconstitution for intravenous administration INDICATION AND USAGE 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). CONTRAINDICATIONS Acute Ischemic Stroke Activase 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 (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 have an elevated activated partial thromboplastin time (aPTT) at presentation —Platelet count < 100,000/mm3 WARNINGS Bleeding The most common complication encountered during Activase therapy is bleeding. The type of bleeding associated with thrombolytic therapy can be divided into two broad categories: • Internal bleeding, involving intracranial and retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts. • Superficial or surface bleeding, observed mainly at invaded or disturbed sites (eg, venous cutdowns, arterial punctures, sites of recent surgical intervention). The concomitant use of heparin anticoagulation may contribute to bleeding. Some of the hemorrhage episodes occurred 1 or more days after the effects of Activase had dissipated, but while heparin therapy was continuing. As fibrin is lysed during Activase therapy, bleeding from recent puncture sites may occur. Therefore, thrombolytic therapy requires careful attention to all potential bleeding sites (including catheter insertion sites, arterial and venous puncture sites, cutdown sites, and needle puncture sites). Intramuscular injections and nonessential handling of the patient should be avoided during treatment with Activase. Venipunctures should be performed carefully and only as required. Should an arterial puncture be necessary during an infusion of Activase, it is preferable to use an upper extremity vessel that is accessible to manual compression. Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding. Should serious bleeding (not controllable by local pressure) occur, the infusion of Activase and any concomitant heparin should be terminated immediately. Each patient being considered for therapy with Activase should be carefully evaluated and anticipated benefits weighed against potential risks associated with therapy. In the following conditions, the risks of Activase therapy for all approved indications may be increased and should be weighed against the anticipated benefits: • Recent major surgery, eg, coronary artery bypass graft, 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 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 (eg, over 75 years old) • Patients currently receiving oral anticoagulants, eg, warfarin sodium • Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location Cholesterol Embolization Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (eg, cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy. Clinical features of cholesterol embolism may include livedo reticularis, “purple toe” syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis. Use in Acute Ischemic Stroke In addition to the previously listed conditions, the risks of Activase therapy to treat acute ischemic stroke may be increased in the following conditions and should be weighed against the anticipated benefits: • 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). In patients without recent use of oral anticoagulants or heparin, Activase treatment can be initiated prior to the availability of coagulation study results. However, infusion should be discontinued if either a pretreatment International Normalized Ratio (INR) > 1.7 or a prothrombin time (PT) > 15 seconds or an elevated activated partial thromboplastin time (aPTT) is identified. Treatment should be limited to facilities that can provide appropriate evaluation and management of ICH. In acute ischemic stroke, neither the incidence of intracranial hemorrhage nor the benefits of therapy are known in patients treated with Activase more than 3 hours after the onset of symptoms. Therefore, treatment of patients with acute ischemic stroke more than 3 hours after symptom onset is not recommended. Trim: 10" ACTIVASE® (Alteplase) Due to the increased risk for 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 neurological deficit or with rapidly improving symptoms prior to the start of Activase administration has not been evaluated. Therefore, treatment of patients with minor neurological deficit or with rapidly improving symptoms is not recommended. PRECAUTIONS General 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. In many cases, patients were receiving concomitant Angiotensin-converting enzyme inhibitors. Patients treated with Activase should be monitored during and for several hours after infusion for signs of orolingual angioedema. If angioedema is noted, promptly institute appropriate therapy (eg, antihistamines, intravenous corticosteroids or epinephrine) and consider discontinuing the Activase infusion. Rare fatal cases of hemorrhage associated with traumatic intubation in patients administered Activase have been reported. Readministration There is no experience with readministration of Activase. 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 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 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 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. Drug Interactions The interaction of Activase 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 therapy. There have been post-marketing reports of orolingual angioedema associated with the use of Activase. 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 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 for the management of acute ischemic stroke is unknown. Blood Pressure Control Blood pressure should be monitored frequently and controlled during and following Activase 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. 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 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 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 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 is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Activase is administered to a nursing woman. Pediatric Use Safety and effectiveness of Activase in pediatric patients have not been established. ADVERSE REACTIONS Bleeding The most frequent adverse reaction associated with Activase in all approved indications is bleeding (see WARNINGS). Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, Activase 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. The incidence of ICH, especially symptomatic ICH, in patients with acute ischemic stroke was higher in Activasetreated patients than placebo patients (see CLINICAL PHARMACOLOGY in the full prescribing information). 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. 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. 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-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 therapy. Therefore, Activase therapy requires careful attention to potential bleeding sites, eg, catheter insertion sites, and arterial puncture sites. Allergic Reactions Allergic-type reactions, eg, anaphylactoid reaction, laryngeal edema, orolingual angioedema, rash, and urticaria have been reported. A cause and effect relationship to Activase 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. 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 in clinical trials and in postmarketing experience. These reactions are frequent sequelae of the underlying disease and the effect of Activase on the incidence of these events is unknown. Use in Acute Ischemic Stroke: Cerebral edema, cerebral herniation, seizure, new ischemic stroke. These events may be life threatening and may lead to death. DOSAGE AND ADMINISTRATION Activase® (Alteplase) is for intravenous administration only. Extravasation of Activase infusion can cause ecchymosis and/or inflammation. Management consists of terminating the infusion at that IV site and application of local therapy. 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.  http://www.urgencytotreatais.com

Table of Contents for the Digital Edition of MD Conference Express ISC 2013

MD Conference Express ISC 2013
Contents
Defending the Stroke Guidelines
Stroke Update: An Overview of What Is Going on in the Area of Stroke
Brain Imaging Does Not Help Identify Patients Who May Benefit From Endovascular Treatments for Acute Ischemic Stroke
MISTIE II Trial: 365-Day Results Demonstrate Improved Outcomes and Cost Benefit
Addition of AMPLATZER PFO Occluder to Medical Therapy Is Beneficial in Patients With Cryptogenic Stroke and PFO
Intraoperative CT-Guided Endoscopic Surgery for ICH [ICES]
The EMBRACE Trial: Prolonged Ambulatory Cardiac Monitoring Improves the Detection and Treatment of Atrial Fibrillation in Patients With Cryptogenic Stroke
DP-b99 Does Not Improve Recovery Following Acute Ischemic Stroke
The Secondary Prevention of Small Subcortical Strokes Trial: Blood Pressure Intervention Results
Final Results of the Solitaire FR Thrombectomy for Acute Revascularization: The STAR Trial
Clopidogrel Plus Aspirin Reduces Risk of Recurrent Stroke: The CHANCE Trial
Reversal of Chronic Hypoperfusion to Improve Cognitive Function: The RECON Trial
Cardioembolic Stroke
IMS III
Novel Anticoagulants in Vascular Neurology Practice
Wake-Up Stroke
Virtual Reality in Stroke Rehabilitation
Reward Improves Long-Term Retention of a Motor Memory Through Induction of Offline Memory Gains

MD Conference Express ISC 2013

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