No

Thrombolytic Agent

Management of acute myocardial infarction (AMI) in adults; lysis of thrombi obstructing coronary arteries; reduction of infarct size

C

Hypersensitivity to anistreplase or streptokinase; active internal bleeding; history of CVA; recent (within 2 months) intracranial or intraspinal surgery or trauma, intracranial neoplasm, arteriovenous malformation, or aneurysm; known bleeding diathesis; severe uncontrolled hypertension

Concurrent heparin anticoagulation can contribute to bleeding; pay careful attention to all potential bleeding site. I.M. injections and nonessential handling of the patient should be avoided. Venipunctures should be performed carefully and only when necessary. If arterial puncture is necessary use an upper extremity vessel that can be manually compressed. If serious bleeding occurs then the infusion of anistreplase and heparin should be stopped.

Coronary thrombolysis may result in reperfusion arrhythmias. Hypotension, occasionally severe, can occur (not from bleeding or anaphylaxis). Follow standard MI management. Rare anaphylactoid reactions can occur. Cautious repeat administration in patients who have received anistreplase or streptokinase within 1 year (antistreptokinase antibody may decrease effectiveness or risk of allergic reactions). Safety and efficacy in pediatric patients have not been established.

As with all drugs which may affect hemostasis, bleeding is the major adverse effect associated with anistreplase. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the dosage administered, concurrent use of multiple agents which alter hemostasis, and patient predisposition. Rapid lysis of coronary artery thrombi by thrombolytic agents may be associated with reperfusion-related atrial and/or ventricular arrhythmias.

Central nervous system: Intracranial hemorrhage (1%)

Cardiovascular: Hypotension (10.4%)

Gastrointestinal: Gastrointestinal hemorrhage (2%), gingival hemorrhage (1%)

Genitourinary: Hematuria (2.4%)

Hematologic: Hematoma (2.8%)

Local: Bleeding at puncture sites (4.6%)

Respiratory: Hemoptysis (2.2%)

<1% (Limited to important or life-threatening symptoms): Anaphylactic reaction, anaphylactoid reaction, bronchospasm, angioedema, urticaria, pruritus, flushing, rash (sometimes with delayed appearance 1-2 weeks after treatment), eosinophilia, arthralgia, pedal edema, proteinuria, vasculitis, Guillain-Barré syndrome, adult respiratory distress syndrome, epistaxis, anemia, ocular hemorrhage

<10% (Unknown causal relationship): Chills, fever, headache, shock, cardiac rupture, emboli, nausea, vomiting, diaphoresis, purpura, thrombocytopenia, elevated transaminases, arthralgia, agitation, dizziness, paresthesia, tremor, vertigo, dyspnea, pulmonary edema

Aminocaproic acid (antifibrinolytic agent) may decrease effectiveness.

Drugs which affect platelet function (eg, NSAIDs, dipyridamole, ticlopidine, clopidogrel, IIb/IIIa antagonists) may potentiate the risk of hemorrhage; use with caution.

Heparin and aspirin: Use with aspirin and heparin may increase the risk of bleeding. However, aspirin and heparin were used concomitantly with anistreplase in the majority of patients in clinical studies. Aspirin was not associated with an increased rate of hemorrhagic CVAs in clinical trials.

Warfarin or oral anticoagulants: Risk of bleeding may be increased during concurrent therapy.

Store between 2°C and 8°C (36°F to 46°F); discard solution 30 minutes after reconstitution if not administered; do not shake solution

Activates the conversion of plasminogen to plasmin by forming a complex exposing plasminogen-activating site and cleavage of a peptide bond that converts plasminogen to plasmin; plasmin being capable of thrombolysis, by degrading fibrin, fibrinogen and other procoagulant proteins into soluble fragments, effective both outside and within the formed thrombus/embolus

Duration of action: Fibrinolytic effect persists for 4-6 hours following administration

Metabolism: Anistreplase is an acylated complex of streptokinase with lys-plasminogen; one of the purposes of this acylation is to extend the serum circulating time of anistreplase; because deacylation of the complex occurs more rapidly than dissociation, fibrinolytic activity is controlled by the rate of deacylation rather than of dissociation

Half-life: 70-120 minutes

Adults: I.V.: 30 units injected over 2-5 minutes as soon as possible after onset of symptoms

It is important that in using thrombolytic therapy in an institution, that the protocol for that institution be followed closely, particularly in terms of dosage, adjunctive heparin therapy, and monitoring of coagulation profiles. It is important that consideration of preceding recent thrombolytic therapy be taken into account when invasive procedures, particularly intravascular procedures, are undertaken. It is important that close clinical monitoring be carried out to ensure efficacy of therapy. Failure of therapy may require emergent cardiac catheterization and interventional therapy. Reperfusion after successful thrombolysis may be associated with rapid resolution of EKG changes and restoration of cardiac function. However, reperfusion arrhythmias may also manifest.

None reported

May cause hypotension which may be exacerbated by psychotropics

No information available to require special precautions

No effects or complications reported

I.V. administration for cardiac emergencies: Patient instruction should be appropriate to situation. Following infusion, absolute bedrest is important; call for assistance changing position. You will have increased tendency to bleed; avoid razors, scissors or sharps, and use soft toothbrush or cotton swabs. Report back pain, abdominal pain, muscle cramping, acute onset headache, chest pain, or bleeding.

Drug should not be used for any condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage

Powder for injection, lyophilized: 30 units