Urokinase - Drug Monograph

Introduction

Urokinase is a thrombolytic (fibrinolytic) agent derived from human kidney cells or recombinant DNA technology. It is a serine protease that directly activates the fibrinolytic system by converting plasminogen to plasmin. Urokinase was one of the first thrombolytic agents developed and remains an important option in specific clinical scenarios, particularly for catheter clearance.

Mechanism of Action

Urokinase acts as a direct activator of the fibrinolytic system. It cleaves the Arg-Val bond in plasminogen to form plasmin, a proteolytic enzyme that degrades fibrin clots, fibrinogen, and other plasma proteins. Unlike streptokinase, urokinase acts directly on the endogenous fibrinolytic system without requiring the formation of an activator complex. It lyses both recently formed thrombi and emboli by breaking down the fibrin matrix that stabilizes platelet aggregates.

Indications

• Catheter clearance: Restoration of patency to occluded intravenous catheters
• Pulmonary embolism: Treatment of acute massive pulmonary emboli with hemodynamic instability
• Coronary artery thrombosis: Off-label use in acute myocardial infarction (largely replaced by newer agents)
• Peripheral arterial thrombosis: Treatment of acute arterial thromboembolism
• Venous thrombosis: Management of deep vein thrombosis

Dosage and Administration

• Instill 5000 IU/mL solution into occluded catheter
• Leave in place for 30-60 minutes, then aspirate
• May repeat once if necessary

• Loading dose: 4400 IU/kg IV over 10 minutes
• Maintenance: 4400 IU/kg/hour for 12 hours

• Regional intra-arterial infusion: 4000-6000 IU/minute until lysis occurs
• Maximum dose: 2,000,000 IU over 2 hours

• Renal impairment: Dose adjustment may be necessary
• Hepatic impairment: Use with caution
• Pediatrics: Limited data; use based on body weight

Pharmacokinetics

• Absorption: Administered intravenously or directly into catheter; complete bioavailability
• Distribution: Volume of distribution approximately 11-13 L; distributes into extracellular fluid
• Metabolism: Primarily hepatic; rapidly inactivated by plasma proteins
• Elimination: Half-life approximately 10-20 minutes; cleared primarily by the liver and kidneys
• Excretion: Degradation products excreted in urine

Contraindications

• Active internal bleeding
• History of cerebrovascular accident
• Intracranial or intraspinal surgery within past 2 months
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Known bleeding diathesis
• Severe uncontrolled hypertension
• Hypersensitivity to urokinase or any component

Warnings and Precautions

• Bleeding risk: Major bleeding can occur at any site; intracranial hemorrhage is most serious
• Arterial puncture sites: Avoid noncompressible arterial puncture during therapy
• Recent surgery: Increased risk of bleeding with recent major surgery
• Cardiac risks: Potential for reperfusion arrhythmias
• Allergic reactions: Although rare, anaphylactoid reactions may occur
• Cholesterol embolization: Possible with thrombolytic therapy
• Pregnancy: Category B; use only if clearly needed

Drug Interactions

• Anticoagulants (heparin, warfarin): Increased risk of bleeding
• Antiplatelet agents (aspirin, clopidogrel): Enhanced bleeding risk
• Other thrombolytics: Additive effects and bleeding risk
• ACE inhibitors: Increased risk of angioedema
• NSAIDs: Potentiated bleeding tendency

Adverse Effects

• Superficial bleeding at puncture sites
• Bruising
• Nausea
• Fever

• Intracranial hemorrhage (0.5-1%)
• Gastrointestinal bleeding
• Retroperitoneal hemorrhage
• Allergic reactions (rare)
• Reperfusion arrhythmias
• Cholesterol embolization syndrome
• Hypotension

Monitoring Parameters

• Vital signs: Continuous monitoring during infusion
• Bleeding assessment: Frequent checks for overt and occult bleeding
• Neurological status: Hourly assessments for signs of intracranial hemorrhage
• Coagulation parameters: aPTT, PT/INR, fibrinogen, fibrin degradation products
• Hemoglobin/hematocrit: Serial measurements
• ECG monitoring: For reperfusion arrhythmias
• Catheter site: Frequent inspection for bleeding or hematoma formation

Patient Education

• Report any signs of bleeding immediately (unusual bruising, blood in urine/stool, headache, dizziness)
• Avoid activities that may cause injury or bleeding during treatment
• Inform all healthcare providers about recent urokinase therapy before any procedures
• Understand the purpose and potential risks of thrombolytic therapy
• Report any allergic reactions (rash, itching, swelling, difficulty breathing)
• Follow all post-treatment instructions regarding activity restrictions and follow-up care

References

1. FDA Prescribing Information: Abbokinase (urokinase) 2. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (2012) 3. TPA and Urokinase Comparison Trial. Circulation. 1988;77:1104-1112 4. Marder VJ, Sherry S. Thrombolytic therapy: current status. N Engl J Med. 1988;318:1512-1520 5. Wardlaw JM, et al. Thrombolysis for acute ischemic stroke. Cochrane Database Syst Rev. 2014;(7) 6. Kearon C, et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-352 7. Lexicomp Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.; 2023 8. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI