No

Thrombolytic Agent

Thrombolytic agent used in treatment of recent severe or massive deep vein thrombosis, pulmonary emboli, myocardial infarction, and occluded I.V. or dialysis cannulas; more expensive than streptokinase; not useful on thrombi over 1 week old

B

Hypersensitivity to urokinase or any component; 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; careful attention to all potential bleeding sites. 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 urokinase and heparin should be stopped.

Coronary thrombolysis may result in reperfusion arrhythmias. Follow standard MI management. Rare anaphylactoid reactions can occur. 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 urokinase. 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.

Local: Injection site bleeding

1% to 10%:

Dermatologic: Bruising

Gastrointestinal: Gastrointestinal hemorrhage, nausea, vomiting

Genitourinary: Genitourinary hemorrhage

Hematologic: Anemia

Neuromuscular and skeletal: Muscle pain

Respiratory: Epistaxis

<1%: Intracranial hemorrhage, retroperitoneal hemorrhage, pericardial hemorrhage, gingival hemorrhage, epistaxis, allergic reactions, fever, chills, anaphylaxis, anaphylactoid reactions, bronchospasm, hypotension, rash, urticaria, back pain, tachycardia

Additional cardiovascular events associated with use in myocardial infarction: AV block, cardiogenic shock, heart failure, cardiac arrest, recurrent ischemia/infarction, myocardial rupture, electromechanical dissociation, pericardial effusion, pericarditis, mitral regurgitation, cardiac tamponade, thromboembolism, pulmonary edema, asystole, ventricular tachycardia.

Symptoms of overdose include epistaxis, bleeding gums, hematoma, spontaneous ecchymoses, oozing at catheter site

In case of overdose, stop infusion, reverse bleeding with blood products that contain clotting factors

Aminocaproic acid (antifibrinolytic agent) may decrease effectiveness.

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

Heparin: Concurrent use may increase risk of bleeding; use caution.

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

Store in refrigerator; reconstitute by gently rolling and tilting; do not shake; contains no preservatives, should not be reconstituted until immediately before using, discard unused portion; stable at room temperature for 24 hours after reconstitution

Promotes thrombolysis by directly activating plasminogen to plasmin, which degrades fibrin, fibrinogen, and other procoagulant plasma proteins

Onset of action: I.V.: Fibrinolysis occurs rapidly

Duration: 4 or more hours

Half-life: 10-20 minutes

Elimination: Cleared by the liver with a small amount excreted in urine and bile

Children and Adults: Deep vein thrombosis: I.V.: Loading: 4400 units/kg over 10 minutes, then 4400 units/kg/hour for 12 hours

Adults:

Myocardial infarction: Intracoronary: 750,000 units over 2 hours (6000 units/minute over up to 2 hours)

Occluded I.V. catheters:

5000 units (use only Abbokinase® Open Cath) in each lumen over 1-2 minutes, leave in lumen for 1-4 hours, then aspirate; may repeat with 10,000 units in each lumen if 5000 units fails to clear the catheter; do not infuse into the patient; volume to instill into catheter is equal to the volume of the catheter

I.V. infusion: 200 units/kg/hour in each lumen for 12-48 hours at a rate of at least 20 mL/hour

Dialysis patients: 5000 units is administered in each lumen over 1-2 minutes; leave urokinase in lumen for 1-2 days, then aspirate

Clot lysis (large vessel thrombi): Loading: I.V.: 4400 units/kg over 10 minutes, increase to 6000 units/kg/hour; maintenance: 4400-6000 units/kg/hour adjusted to achieve clot lysis or patency of affected vessel; doses up to 50,000 units/kg/hour have been used. Note: Therapy should be initiated as soon as possible after diagnosis of thrombi and continued until clot is dissolved (usually 24-72 hours).

Acute pulmonary embolism: Three treatment alternatives: 3 million unit dosage

Alternative 1: 12-hour infusion: 4400 units/kg (2000 units/lb) bolus over 10 minutes followed by 4400 units/kg/hour (2000 units/lb); begin heparin 1000 units/hour approximately 3-4 hours after completion of urokinase infusion or when PTT is <100 seconds

Alternative 2: 2-hour infusion: 1 million unit bolus over 10 minutes followed by 2 million units over 110 minutes; begin heparin 1000 units/hour approximately 3-4 hours after completion of urokinase infusion or when PTT is <100 seconds

Alternative 3: Bolus dose only: 15,000 units/kg over 10 minutes; begin heparin 1000 units/hour approximately 3-4 hours after completion of urokinase infusion or when PTT is <100 seconds

CBC, reticulocyte count, platelet count, DIC panel (fibrinogen, plasminogen, FDP, D-dimer, PT, PTT), thrombosis panel (AT-III, protein C), urinalysis, ACT

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 standard myocardial infarction therapy (aspirin, beta-blocker, ACE inhibitor). 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

None reported

No information available to require special precautions

No effects or complications reported

You will require frequent blood tests. Report any signs of unusual bleeding. Use electric razor and soft toothbrush. Breast-feeding precautions: Consult prescriber if breast-feeding.

Use 0.22 or 0.45 micron filter during I.V. systemic therapy; I.V. infusion: Usual concentration: 1250-1500 units/mL; maximum concentration not yet defined

Powder for injection: 250,000 units (5 mL)

Powder for injection, catheter clear: 5000 units (1 mL)

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Michelson AD, Bovill E, Monagle P, et al, "Antithrombotic Therapy in Children," Chest, 1998, 114(5 Suppl):748S-69S.

Panteghini M and Pagani F, "Isoforms of Creatine Kinase Isoenzymes in Serum in Acute Myocardial Infarction After Intracoronary Thrombolysis," Clin Chem, 1987, 33(11):2039-42.

Pavlou H, Panagiotopoulos A, Graham A, and Alexopoulous D, "Urokinase-Induced Cyto-Hepatolysis in a Patient With Acute Myocardial Infarction," Eur Heart J, 1995, 16(2):291-2.

Suarez CR, Ow EP, Lambert GH, et al, "Urokinase Therapy for a Central Venous Catheter Thrombus," Am J Hematol, 1989, 31(4):269-72.

Tenney RD and Sasahara AA, "Urokinase Dissolution of a Right Atrial Thrombus," Arch Intern Med, 1989, 149(2):475.