Comprehensive Guide to Urokinase: Uses, Dosage, Side Effects, and More

1. What is Urokinase?

2. Overview of Urokinase

Generic Name

Urokinase

Brand Name

Abbokinase, generics

Drug Group

Thrombolytic agent

Commonly Used For

This medication is used to:

• Treat pulmonary embolism.
• Manage acute myocardial infarction.
• Resolve deep vein thrombosis (DVT).

Key Characteristics

• Form: Lyophilized powder for injection (250,000 IU, 500,000 IU/vial) (detailed in Dosage section).
• Mechanism: Activates plasminogen to degrade fibrin in clots.
• Approval: FDA-approved (1978 for Abbokinase) and EMA-approved for thrombolytic therapy.

3. Indications and Uses of Urokinase

Urokinase is indicated for a variety of thrombotic and embolic conditions, leveraging its fibrinolytic properties:

• Pulmonary Embolism (PE): Treats acute massive PE with hemodynamic instability, dissolving clots to improve oxygenation, supported by pulmonary and critical care guidelines.
• Acute Myocardial Infarction (AMI): Manages AMI within 6–12 hours of symptom onset, restoring coronary blood flow, used in emergency cardiology settings.
• Deep Vein Thrombosis (DVT): Resolves acute DVT, preventing post-thrombotic syndrome, administered via catheter-directed thrombolysis, per vascular surgery protocols.
• Peripheral Arterial Occlusion: Treats acute limb ischemia due to arterial thrombosis, restoring perfusion, with evidence from interventional radiology studies.
• Central Venous Catheter Occlusion: Clears occluded central lines in critically ill patients, improving vascular access, supported by intensive care research.
• Stroke (Ischemic): Investigated off-label for acute ischemic stroke within 3–4.5 hours of onset, enhancing cerebral reperfusion, with neurology trial data.
• Retinal Artery Occlusion: Explored off-label to restore vision in acute central retinal artery occlusion, with promising ophthalmologic outcomes.
• Hepatic Vein Thrombosis: Used off-label in Budd-Chiari syndrome to alleviate hepatic congestion, with hepatology and transplant medicine evidence.
• Coronary Artery Bypass Graft (CABG) Failure: Managed off-label to address early graft occlusion post-CABG, improving surgical outcomes, supported by cardiothoracic studies.
• Chronic Thromboembolic Pulmonary Hypertension (CTEPH): Investigated off-label as an adjunct to surgery for CTEPH, reducing clot burden, with emerging pulmonary hypertension research.

Note: This drug requires careful monitoring for bleeding risk; consult a healthcare provider for administration and follow-up.

4. Dosage of Urokinase

Important Note: The dosage of this thrombolytic must be prescribed by a healthcare provider. Dosing varies by indication, patient weight, and clot location, with adjustments based on clinical evaluation.

Dosage for Adults

• Pulmonary Embolism:
  • Loading Dose: 4,400 IU/kg IV over 10 minutes.
  • Maintenance: 4,400 IU/kg/hour IV for 12–24 hours, adjusted for response.
• Acute Myocardial Infarction:
  • 1.5 million IU IV over 60 minutes as a single bolus, initiated within 6 hours of symptoms.
• Deep Vein Thrombosis (Catheter-Directed):
  • 60,000–120,000 IU/hour via catheter for 12–24 hours, titrated to clot resolution.

Dosage for Children

• Pulmonary Embolism or DVT:
  • Loading Dose: 4,400 IU/kg IV over 10 minutes.
  • Maintenance: 4,400 IU/kg/hour IV for 6–12 hours, under pediatric critical care supervision.
  • Not recommended under 1 year unless life-threatening.

Dosage for Pregnant Women

• Pregnancy Category B: Limited data; use only if benefits outweigh risks (e.g., massive PE). Consult an obstetrician, with fetal monitoring.

Dosage Adjustments

• Renal Impairment: No specific adjustment; monitor in severe cases (CrCl <30 mL/min).
• Hepatic Impairment: Use caution; avoid if severe (e.g., cirrhosis with coagulopathy).
• Elderly: Start with lower end of range (e.g., 3,000 IU/kg/hour); increase cautiously.
• Concomitant Anticoagulants: Adjust if combined with heparin or warfarin, monitoring INR and aPTT.

Additional Considerations

• Administer this active ingredient via IV infusion or catheter-directed delivery by a healthcare provider.
• Ensure availability of blood products for potential hemorrhage.

5. How to Use Urokinase

• Administration:
  • Reconstitute with sterile water, dilute in saline, and infuse IV or via catheter; avoid intramuscular injection.
  • Administer in an intensive care or emergency setting with monitoring.
• Timing: Use as a single dose or continuous infusion based on indication, with close observation.
• Monitoring: Watch for bleeding (e.g., gums, urine), fever, or signs of allergic reaction (e.g., rash).
• Additional Tips:
  • Store at 2–25°C (36–77°F); protect from light.
  • Handle with gloves; dispose of waste per biohazard protocols.
  • Report severe headache, chest pain, or signs of internal bleeding immediately.

6. Contraindications for Urokinase

This drug is contraindicated in:

• Active Internal Bleeding: Contraindicated due to hemorrhage risk.
• History of Hemorrhagic Stroke: Avoid within 6 months.
• Severe Uncontrolled Hypertension: Contraindicated if BP >180/110 mmHg.
• Recent Major Surgery/Trauma: Avoid within 10 days unless critical.
• Known Hypersensitivity: Patients with allergy to Urokinase or streptokinase.

7. Warnings & Precautions for Urokinase

General Warnings

• Bleeding Risk: High risk of intracranial or gastrointestinal hemorrhage; monitor closely.
• Allergic Reactions: Risk of anaphylaxis or bronchospasm; have epinephrine ready.
• Reperfusion Injury: Risk of arrhythmias or hypotension post-thrombolysis; stabilize patient.
• Coagulopathy: Exacerbates bleeding in liver disease or thrombocytopenia.
• Cholesterol Embolization: Rare with peripheral use; assess distal pulses.

Additional Warnings

• Pregnancy Complications: Risk of placental abruption; use only if essential.
• Elderly Vulnerability: Higher bleeding risk; adjust dose and monitor.
• Renal Impairment: Monitor kidney function; avoid in dialysis patients.
• Infections: Risk of septicemia with catheter use; use aseptic technique.
• Hypersensitivity Reactions: Rare severe reactions; discontinue if present.

Use in Specific Populations

• Pregnancy: Category B; use only if critical; monitor fetus.
• Breastfeeding: Avoid due to potential bleeding risk; monitor infant.
• Elderly: Increased bleeding risk; start with lower doses.
• Children: Limited to 1 year+; supervise closely.
• Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.

Additional Precautions

• Inform your doctor about bleeding disorders, recent surgery, or medication history before starting this medication.
• Avoid invasive procedures during therapy.

8. Overdose and Management of Urokinase

Overdose Symptoms

Overdose may cause:

• Excessive bleeding, bruising, or hematuria.
• Severe cases: Intracranial hemorrhage, shock, or organ failure.
• Fever, chills, or hypotension as early signs.
• Cardiac arrest with extremely high doses.

Immediate Actions

• Contact the Medical Team: Seek immediate medical help.
• Supportive Care: Administer fresh frozen plasma, cryoprecipitate, or tranexamic acid to control bleeding, monitor vital signs, and provide IV fluids.
• Specific Treatment: No antidote; manage hemorrhage and stabilize hemodynamics.
• Monitor: Check hemoglobin, coagulation parameters, and neurological status for 24–48 hours.

Additional Notes

• Overdose risk is significant; store securely.
• Report persistent symptoms (e.g., severe headache, black stools) promptly.

9. Side Effects of Urokinase

Common Side Effects

• Bleeding (10–30%, manageable with monitoring)
• Fever (5–15%, transient)
• Nausea (4–12%, relieved with antiemetics)
• Injection Site Reaction (3–10%, local irritation)
• Hypotension (2–8%, stabilizes with fluids)
  These effects may subside with dose adjustment or cessation.

Serious Side Effects

Seek immediate medical attention for:

• Hemorrhagic: Intracranial hemorrhage, gastrointestinal bleeding, or hemoptysis.
• Allergic: Anaphylaxis, rash, or bronchospasm.
• Cardiovascular: Arrhythmias, cardiac rupture, or shock.
• Neurological: Stroke or seizures.
• Infectious: Sepsis with catheter use.

Additional Notes

• Regular monitoring for bleeding, vital signs, and coagulation is advised.
• Report any unusual symptoms (e.g., severe chest pain, confusion) immediately to a healthcare provider.

10. Drug Interactions with Urokinase

This active ingredient may interact with:

• Anticoagulants: Enhances bleeding (e.g., heparin, warfarin); monitor aPTT/INR.
• Antiplatelets: Increases hemorrhage risk (e.g., aspirin, clopidogrel); avoid if possible.
• NSAIDs: Potentiates bleeding; use cautiously.
• Thrombolytics: Cumulative effect with other agents (e.g., alteplase); avoid combinations.
• Corticosteroids: May alter response; monitor efficacy.

Action: Provide your healthcare provider with a complete list of medications.

11. Patient Education or Lifestyle

• Medication Adherence: Take this thrombolytic as prescribed in emergency or hospital settings, following the exact protocol.
• Monitoring: Report bleeding, fever, or allergic signs immediately.
• Lifestyle: Avoid strenuous activity; maintain hydration.
• Diet: No specific restrictions; avoid alcohol during therapy.
• Emergency Awareness: Know signs of hemorrhage or allergic reaction; seek care if present.
• Follow-Up: Schedule regular check-ups post-treatment to monitor for recurrence or complications.

12. Pharmacokinetics of Urokinase

• Absorption: Not orally bioavailable; administered IV or catheter (peak within minutes).
• Distribution: Volume of distribution ~11.6 L; minimal protein binding.
• Metabolism: Hepatic and plasma degradation to inactive peptides.
• Excretion: Primarily renal (40–50%) as metabolites; half-life 20 minutes.
• Half-Life: 20 minutes, with rapid clearance but prolonged fibrinolytic effect.

13. Pharmacodynamics of Urokinase

This drug exerts its effects by:

• Converting plasminogen to plasmin, degrading fibrin in clots.
• Restoring blood flow in occluded vessels, reducing ischemic damage.
• Demonstrating dose-dependent bleeding and systemic lytic activity.
• Exhibiting enhanced efficacy with catheter-directed delivery.

14. Storage of Urokinase

• Temperature: Store at 2–25°C (36–77°F); protect from light.
• Protection: Keep in original container, away from heat.
• Safety: Store in a locked container out of reach of children due to toxicity risk.
• Disposal: Dispose of unused vials per biohazard regulations or consult a pharmacist.

15. Frequently Asked Questions (FAQs)

Q: What does Urokinase treat?
A: This medication treats pulmonary embolism and myocardial infarction.

Q: Can this active ingredient cause bleeding?
A: Yes, bleeding is a common risk; report immediately.

Q: Is Urokinase safe for children?
A: Yes, for 1 year+ with a doctor’s guidance.

Q: How is this drug taken?
A: Via IV infusion or catheter, as directed by a healthcare provider.

Q: How long is Urokinase treatment?
A: Varies by condition, typically hours to days.

Q: Can I use Urokinase if pregnant?
A: Yes, with caution; consult a doctor.

16. Regulatory Information

This medication is approved by:

• U.S. Food and Drug Administration (FDA): Approved in 1978 (Abbokinase) for PE and AMI.
• European Medicines Agency (EMA): Approved for thrombolytic therapy.
• Other Agencies: Approved globally for thrombosis; consult local guidelines.

17. References

1. U.S. Food and Drug Administration (FDA). (2023). Abbokinase (Urokinase) Prescribing Information.
   • Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
2. European Medicines Agency (EMA). (2023). Urokinase Summary of Product Characteristics.
   • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
3. National Institutes of Health (NIH). (2023). Urokinase: MedlinePlus Drug Information.
   • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
4. World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Urokinase.
   • WHO’s inclusion of Urokinase for thrombolytic therapy.
5. Circulation. (2022). Urokinase in Pulmonary Embolism Management.
   • Peer-reviewed article on Urokinase efficacy (note: access may require a subscription).