Alteplase administration

Alteplase Administration Protocol for Cerebrovascular Accident Indication... 

Immunologic A patient experienced anaphylaxis after an initial bolus and subsequent delayed infusion of alteplase for thrombolysis of acute ischaemic stroke. Although rare, anaphylaxis is a recognized adverse event with alteplase administration, and infusion should be ceased following any symptoms of an anaphylactic reaction to avoid a dose-dependent major reaction [34 ]. 

Alteplase (rt-PA Activase) is an IV thrombolytic (fibrinolytic) that was approved for acute stroke treatment in 1996 based on the results of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial.10 The current American Stroke Association guidelines include alteplase as the only Food and Drug Administration (FDA) approved acute treatment for ischemic stroke and strongly encourage early diagnosis and treatment of appropriate patients.11... 

Pharmacologic management of thrombosis includes local administration of thrombolytic agents. Alteplase (2 mg per port) and reteplase (0.5 unit per port) are the two most commonly used agents today. Urokinase has been used in the past, but after its reintroduction to the United States market, the larger dosed vial size makes it less cost effective than the newer agents. 

Alteplase has proven effective in the early treatment of patients with acute myocardial infarction (i.e. those treated within 12 h after the first symptoms occur). Significantly increased rates of patient survival (as measured 1 day and 30 days after the initial event) are noted when tPA is administered in favour of streptokinase, a standard therapy (see later). tPA has thus established itself as a first-line option in the management of acute myocardial infarction. A therapeutic dose of 90-100 mg (often administered by infusion over 90 min) results in a steady-state alteplase concentration of 3-4 mg l 1 during that period. However, the product is cleared rapidly by the liver, displaying a serum half-life of approximately 3 min. As is the case for most thrombolytic agents, the most significant risk associated with tPA administration is the possible induction of severe haemorrhage. 

Intracranial bleeding Following concomitant thrombolytic therapy with alteplase (tPA) or streptokinase may be life-threatening. Carefully assess the risk of lepirudin administration vs its anticipated benefit in patients with increased risk of bleeding. In particular, this includes the following conditions ... 

Dosage form Activase is a sterile, lyophilized powder for intravenous administration after reconstitution with sterile water for injection. Each vial contains alteplase 50 or 100 mg. 

F. Role in therapy Reteplase is a novel thrombolytic agent. It has a longer half-life than alteplase, which allows bolus administration. Its administration technique is much simpler than that of alteplase. In addition reteplase has achieved more rapid, complete, and sustained thrombolysis of the infarct-related artery compared to standard doses of alteplase with comparable safety. Reteplase is at least as effective as streptokinase and alteplase in AMI. 

E Role in therapy Thrombolytic agents currently licensed for the treatment of AMI in the United States include streptokinase, tissue plasminogen activator, anistreplase, reteplase, and tenecteplase. TNKase and alteplase have similar clinical efficacy for thrombolysis after myocardial infarction (i.e., similar mortality and intracranial hemorrhage rates). However, advantages of TNKase include ease and rapidity of administration, longer half-life, greater fibrin specificity, and lower noncerebral bleeding rates. Reteplase shares some characteristics of tenecteplase (e.g., similar half-life, rapid onset, and ease of administration). 

GLYCOPROTEIN lib/ Ilia INHIBITORS THROMBOLYTICS 1. t risk of major haemorrhage when co-administered with alteplase 2. Possible t risk of bleeding complications when streptokinase is co-administered with eptifibatide 1. Uncertain other thrombolytics do not seem to interact 2. Additive effect 1. Avoid co-administration 2. Watch for bleeding complications. Risk-benefit analysis is needed before co-administering this will involve the availability of alternative therapies such as primary angioplasty... 

Pro-urokinase, alteplase, reteplase, and tenecteplase, which are recombinant products, also appear to be free from allergic reactions. Pro-urokinase and alteplase have short half-lives (3-8 minutes) and require continuous infusion administration, which may in some cases be an advantage as it allows rapid surgical intervention when necessary (53). Reteplase and tenecteplase have substantially longer half-lives, allowing bolus administration. 

The Continuous Infusion versus Double-Bolus Administration of Alteplase (COBALT) Investigators. A comparison of continuous infusion of alteplase with double bolus administration for acute myocardial infarction. N Engl J Med 1997 337 1127-1130. 

Smalling RW, Bode C, Kalbfleisch J, et al. More rapid, complete, and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction. RAPID Investigators. Circulation 1995 91 2725-2732. 

Haematologic Intravenous administration of recombinant tissue plasminogen activator (rtPA), also known as alteplase, is a common component of ischaemic stroke management, but its use is associated with intracranial haemorrhage in 6.4% of patients. A 51-year-old woman who had received IV rtPA for acute left middle cerebral artery thromboembolism later presented with subarachnoid haemorrhage from an acutely ruptured anterior communicating artery aneurysm. The patient xmderwent mechanical thromboembolectomy of the left middle cerebral artery occlusion with recanalization followed by coil embolization of the aneurysm, but she did not improve neurologjcally and ultimately died (32). ... 

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