Actilyse50 mg/vial

Acute Ischemic Stroke: Actilyse 50 mg/vial 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 ... Read moreAcute Ischemic Stroke: Actilyse 50 mg/vial 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.Acute Myocardial Infarction: Actilyse 50 mg/vial is indicated for use in acute myocardial infarction (AMI) for the reduction of mortality and the reduction of the incidence of heart failure.Pulmonary Embolism: Actilyse 50 mg/vial is indicated for the lysis of acute massive pulmonary embolism, 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.

Anti-platelet drugs, Fibrinolytics (Thrombolytics)

Actilyse 50 mg/vial works by dissolving clots in the blood vessels. Actilyse 50 mg/vial binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.

Acute Ischemic Stroke: Administer Actilyse 50 mg/vial as soon as possible but within 3 hours after onset of symptoms. The recommended dose is 0.9 mg/kg (not to exceed 90 mg total dose), with 10% of the total dose administered as an initial intravenous bolus over 1 minute and the remainder infused over 60 minutes. During and following Actilyse 50 mg/vial administration for the treatment of acute ischemic stroke, frequently monitor and control blood pressure. In patients without recent use of oral anticoagulants or heparin, Actilyse 50 mg/vial treatment can be initiated prior to the availability of coagulation study results. Discontinue Actilyse 50 mg/vial if the pretreatment International Normalized Ratio (INR) is greater than 1.7 or the activated partial thromboplastin time (aPTT) is elevated.Acute Myocardial Infarction: Administer Actilyse 50 mg/vial as soon as possible after the onset of symptoms. The recommended total doses for acute myocardial infarction (AMI) is based on patient weight, not to exceed 100 mg, regardless of the selected administration regimen (accelerated or 3 hour). There are two Actilyse 50 mg/vial dose regimens (accelerated and 3-hour) for use in the management of AMI; there are no controlled studies to compare clinical outcomes with these regimensPulmonary Embolism (PE): The recommended dose is 100 mg administered by IV infusion over 2 hours. Institute parenteral anticoagulation near the end of or immediately following the Actilyse 50 mg/vial infusion when the partial thromboplastin time or thrombin time returns to twice normal or less.

Following bolus dose, if indicated: 50 mg vials: administer using either a polyvinyl chloride bag or glass vial and infusion set. 100 mg vials: 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 Actilyse 50 mg/vial. Peel the clear plastic hanger from the vial label. Hang the Actilyse 50 mg/vial vial from the resulting loop. Actilyse 50 mg/vial is for intravenous administration only. Extravasation of Actilyse 50 mg/vial infusion can cause ecchymosis or inflammation. If extravasation occurs, terminate the infusion at that IV site and apply local therapy. Do not add any other medication to infusion solutions containing Actilyse 50 mg/vial.

The interaction of Actilyse 50 mg/vial with other cardioactive or cerebroactive drugs has not been studied. Anticoagulants and antiplatelet drugs increase the risk of bleeding if administered prior to, during, or after Actilyse 50 mg/vial therapy. In the post-marketing setting, there have been reports of orolingual angioedema in patients (primarily patients with AIS) receiving concomitant angiotensin-converting enzyme inhibitors.

Acute Ischemic Stroke: Do not administer Actilyse 50 mg/vial to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit [see Warnings and Precautions (5.1)]: Current intracranial hemorrhage 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 Current severe uncontrolled hypertension. Acute Myocardial Infarction or Pulmonary Embolism: Do not administer Actilyse 50 mg/vial for treatment of AMI or PE 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 (e.g. some neoplasms, arteriovenous malformations, or aneurysms) Bleeding diathesis Current severe uncontrolled hypertension.

The following adverse reactions are: Bleeding  Orolingual Angioedema  Cholesterol Embolization Reembolization of Deep Venous Thrombi during Treatment for Acute Massive Pulmonary Embolism.

Pregnancy category B1. Studies with Actilyse 50 mg/vial have not been performed to determine effect on fertility or reproduction.Use in Lactation: It is not known whether Actilyse 50 mg/vial is excreted in human milk. Because many drugs are excreted by this route, caution should be exercised when Actilyse 50 mg/vial is administered to breastfeeding women.

Increases the risk of bleeding. Avoid intramuscular injections. Monitor for bleeding. If serious bleeding occurs, discontinue Actilyse 50 mg/vial. Monitor patients during and for several hours after infusion for orolingual angioedema. If angioedema develops, discontinue Actilyse 50 mg/vial. Cholesterol embolism has been reported rarely in patients treated with thrombolytic agents. Consider the risk of reembolization from the lysis of underlying deep venous thrombi in patients with pulmonary embolism.

Store lyophilized Actilyse 50 mg/vial at controlled room temperature not to exceed 30°C, or under refrigeration (2-8°C). Protect the lyophilized material during extended storage from excessive exposure to light. If stored between 2-30°C, Actilyse 50 mg/vial may be used within 8 hours following reconstitution. Discard any unused solution after administration is complete. Do not use beyond the expiration date stamped on the vial.

Use in the Elderly: The risks of therapy may be increased in the elderly. In a pooled analysis of randomised controlled clinical trials, patients over 80 years was associated with an increased risk of haemorrhage (both ICH and symptomatic ICH), mortality and decreased efficacy compared to younger patientsPaediatric use: Safety and effectiveness of Actilyse 50 mg/vial in children has not been established. Therefore treatment of such patients is not recommended. Actilyse 50 mg/vial is not indicated for treatment of acute stroke in patients less than 18 years of age.

Anti-platelet drugs, Fibrinolytics (Thrombolytics)

Actilyse 50 mg/vial is a serine protease responsible for fibrin-enhanced conversion of plasminogen to plasmin. It produces limited conversion of plasminogen in the absence of fibrin. When introduced into the systemic circulation at pharmacologic concentration, Actilyse 50 mg/vial binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. This initiates local fibrinolysis with limited systemic proteolysis.Pharmacodynamics: Following administration of 100 mg Actilyse 50 mg/vial, there is a decrease (16%-36%) in circulating fibrinogen. In a controlled trial, 8 of 73 patients (11%) receiving Actilyse 50 mg/vial (1.25 mg/kg body weight over 3 hours) experienced a decrease in fibrinogen to below 100 mg/dL.Pharmacokinetics: Actilyse 50 mg/vial in acute myocardial infarction (AMI) patients is rapidly cleared from the plasma with an initial half-life of less than 5 minutes. There is no difference in the dominant initial plasma half-life between the 3-hour and accelerated regimens for AMI. The plasma clearance of Actilyse 50 mg/vial is 380-570 mL/min, primarily mediated by the liver. The initial volume of distribution approximates plasma volume.

Pregnancy Category C. Actilyse 50 mg/vial is embryocidal 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. It is not known whether Actilyse 50 mg/vial is excreted in human milk. Many drugs are excreted in human milk.

Pediatric Use: Safety and effectiveness of Actilyse 50 mg/vial in pediatric patients have not been established.Geriatric Use: Acute Ischemic Stroke: In exploratory, multivariate analyses of Studies 1 and 2, age greater than 77 years was one of several interrelated baseline characteristics associated with an increased risk of intracranial hemorrhage. Efficacy results suggest a reduced but still favorable clinical outcome for Actilyse 50 mg/vial-treated elderly. Acute Myocardial Infarction: In a large trial of accelerated-infusion Actilyse 50 mg/vial that enrolled 41,021 patients with AMI to one of four thrombolytic regimens [see Clinical Studies (14.2)], patients over 75 years of age, a predefined subgroup, comprised 12% of enrolment. In these patients, the incidence of stroke was 4.0% for the Actilyse 50 mg/vial accelerated infusion group, 2.8% for streptokinase IV [SK (IV)], and 3.2% for streptokinase SQ [SK (SQ)]. The incidence of combined 30-day mortality or nonfatal stroke was 20.6% for accelerated infusion of Actilyse 50 mg/vial, 21.5% for SK (IV), and 22.0% for SK (SQ).