Actilyse

Thrombolytic treatment in acute myocardial infarction, acute massive pulmonary embolism with haemodynamic instability, Fibrinolytic treatment of acute ischaemic stroke

Intravenous Acute Myocardial Infarction Administer as soon as possible after onset of symptoms Recommended total dose for AMI is based on patient weight, not to exceed 100 mg, regardless of the selected administration regimen (accelerated or 3 hr) Accelerated infusion (1-1/2 hr) <67 kg: 15 mg IVP bolus over 1-2 minutes, THEN 0.75 mg/kg IV infusion over 30 minutes (not to exceed 50 mg), and THEN 0.5 mg/kg IV over next 60 minutes (not to exceed 35 mg over 1 hr) >67 kg (100 mg total dose infused over 1.5 hr): 15 mg IVP bolus over 1-2 minutes, THEN 50 mg IV infusion over next 30 minutes, and THEN remaining 35 mg over next 60 minutes 3-hr infusion <65 kg: 0.075 mg/kg IVP bolus over 1-2 minutes, THEN 0.675 mg/kg infused over the rest of the first hr, THEN 0.25 mg/kg IV for the next 2 hr >65 kg: (100 mg total dose infused over 3 hr): 6-10 mg IVP bolus over 1-2 minutes, THEN 50-54 mg infused over the rest of the first hr (ie, 60 mg in 1st hr including 6-10 mg bolus), THEN 20 mg/hr for the next 2 hr Pulmonary Embolism 100 mg IV infused over 2 hr; institute parenteral anticoagulation near the end of or immediately following alteplase infusion when the PTT or thrombin time returns to <2x normal Acute Ischemic Stroke 0.9 mg/kg IV; not to exceed 90 mg total dose; administer 10% of the total dose as an initial IV bolus over 1 minute and the remainder infused over 60 minutes Injection Central Venous Catheter Occlusion 2 mg in 2 mL instilled into occluded catheter Assess catheter function after 30 minutes of dwell time by attempting to aspirate blood; if unable to aspirate after 120 minutes dwell time, a 2nd dose may be administered and the process repeated If catheter function restored, aspirate 4-5 mL blood to remove Cathflo Activase and residual clot Gently irrigate with 0.9% NaCl

Central Venous Catheter Occlusion <30 kg Instill 110% of the internal lumen volume of the catheter; not to exceed 2 mg in 2 mL >30 kg 2 mg instilled into occluded catheter Assess catheter function after 30 minutes of dwell time by attempting to aspirate blood; if unable to aspirate after 120 minutes dwell time, a 2nd dose may be administered and the process repeated If catheter function restored, aspirate 4-5 mL blood in patients 10 kg or more (aspirate 3 mL if <10 kg) to remove injection solution and residual clot Gently irrigate with 0.9% NaCl

Known hyper-sensitivity to Alteplase or any component of the formulation. Acute Ischemic Stroke Do not administer to treat acute ischemic stroke in the following situations in which the risk of bleeding is greater than the potential benefit 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 (eg, some neoplasms, arteriovenous malformations, aneurysms) Bleeding diathesis Current severe uncontrolled hypertension Acute myocardial infarction or pulmonary embolism Do not administer 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 (eg, some neoplasms, arteriovenous malformations, aneurysms) Bleeding diathesis Current severe uncontrolled hypertension

Recombinant human tissue-type plasminogen activator (t-PA); produces local fibrinolysis Promotes thrombolysis by converting plasminogen to plasmin; plasmin degrades fibrin and fibrinogen

Use caution in recent major surgery, cerebrovascular disease, HTN, acute pericarditis, hemostatic defects, severe thrombophlebitis, severe hepatic/renal dysfunction Avoid intramuscular injections Monitor for bleeding; discontinue therapy if serious bleeding occurs Monitor patients during and for several hours after infusion for orolingual angioedema; discontinue therapy if angioedema develops Cholesterol embolism reported rarely in patients treated with thrombolytic agents Consider risk of reembolization from lysis of underlying deep venous thrombi in patients with pulmonary embolism Internal bleeding (intracranial, retroperitoneal, gastrointestinal, genitourinary, respiratory) or external bleeding, especially at arterial and venous puncture sites may occur Avoid intramuscular injections and trauma to patient while on therapy Perform venipunctures carefully and only as required Minimize bleeding from noncompressible sites by avoiding internal jugular and subclavian venous punctures If arterial puncture necessary during therapy infusion, use upper extremity vessel that is accessible to manual compression, apply pressure for at least 30 min, and monitor puncture site closely Patients treated for acute ischemic stroke, with high risk of intracranial hemorrhage, should be treated at facilities that can provide timely access to appropriate evaluation and management of intracranial hemorrhage Coronary thrombolysis may result in reperfusion arrhythmias Patients who present within 3 hr of stroke symptom onset, should be treated with alteplase unless contraindications exist; longer time window (3-4.5 hr after symptom onset) shown to be safe and efficasious for select individuals; treatment of patients with minor neurological symptoms not recommended Alteplase does not treat adequately underlying deep vein thromposis in patients with pulmonary embolism; consider possible risk of re-embolization due to lysis of underlying deep venous thrombi in this setting Lactation: Excretion in milk unknown; use with caution

1-10% Stroke (1.6%) Frequency Not Defined Accelerated idioventricular rhythm,Pulmonary edema,Arterial embolism,Bruising,Bleeding,DVT,Hypotension,Intracranial hemorrhage,GI/GU hemorrhage,Pulmonary embolism,Fever/chills,Nausea/vomiting,Sensitivity reaction,Sepsis,Shock

Pregnancy Published studies and case reports on alteplase use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes; alteplase is embryocidal in rabbits when intravenously administered during organogenesis at clinical exposure for AMI, but no maternal or fetal toxicity was evident at lower exposure in pregnant rats or rabbits; the most common complication of thrombolytic therapy is bleeding; pregnancy may increase this risk; drug should be used during pregnancy only if potential benefit justifies potential risk to fetus Lactation There are no data on presence of alteplase in human milk, effects on breastfed infant, or on milk production

The risk of haemorrhage is increased if coumarine derivatives, oral anticoagulants, platelet aggregation inhibitors, unfractionated heparin or LMWH or active substances which interfere with coagulation are administered (before, during or within the first 24 hours after treatment with Alteplase). Concomitant treatment with ACE inhibitors may enhance the risk of suffering an anaphylactoid reaction, as in the cases describing such reactions a relatively larger proportion of patients were receiving ACE inhibitors concomitantly. Concomitant use of GPIIb/IIIa antagonists increases the risk of bleeding.