Usage
Urokinase is prescribed for the treatment of acute massive pulmonary embolism. It is also used for lysis of pulmonary emboli, coronary artery thrombi, and various other conditions involving blood clots like peripheral arterial occlusion and central venous catheter clearance. Pharmacologically, urokinase is classified as a thrombolytic agent. It acts by activating plasminogen to form plasmin, which in turn degrades fibrin, the primary component of thrombi (blood clots), thereby dissolving them.
Alternate Names
Urokinase is also known as serine protease and is sometimes referred to by brand names such as Kinlytic™.
How It Works
Pharmacodynamics: Urokinase exerts its thrombolytic effect by converting plasminogen to plasmin. Plasmin then degrades fibrin, leading to thrombolysis.
Pharmacokinetics: Urokinase is administered intravenously or intra-arterially and does not undergo significant metabolism. It is cleared primarily through hepatic and renal pathways.
Mode of Action: Urokinase directly activates plasminogen. This process does not involve receptor binding, enzyme inhibition, or neurotransmitter modulation.
Elimination: Urokinase is cleared through renal excretion with minimal hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Pulmonary Embolism (Intravenous): A loading dose of 4,400 IU/kg over 10 minutes, followed by a continuous infusion of 4,400 IU/kg/hour for 12-24 hours or 100,000 IU/hour for 48-72 hours, depending on the indication and product-specific guidelines. Alternative dosing regimens for PE include an initial bolus of 4,400 IU/kg over 10-20 minutes followed by a continuous infusion of 4,400 IU/kg/hour for 12 hours, or an initial bolus injection into the pulmonary artery repeated up to two times at 24-hour intervals.
- Peripheral Arterial Thromboembolism (Intra-arterial): 4,000 IU/minute for 2-4 hours, then 1,000-2,000 IU/minute until lysis is complete.
Children:
Limited data are available for pediatric dosing. Use with caution and adjust according to patient weight, age and medical condition. Dosing similar to adults but adjusted based on weight and clinical response is sometimes used. For intrapleural use in empyema, 40,000 units in 40 mL 0.9% saline is suggested for children ≥10 kg and 10,000 units in 10 mL 0.9% saline for those <10 kg, administered twice daily for three days. For catheter clearance, the concentration can vary between 5,000–10,000 IU/mL or 4,400 IU/kg.
Special Cases:
- Elderly Patients: Exercise caution; begin with lower doses and adjust as needed.
- Patients with Renal Impairment: Close monitoring required, dose adjustments are needed depending upon creatinine clearance.
- Patients with Hepatic Dysfunction: Reduce the dose and closely monitor coagulation parameters.
- Patients with Comorbid Conditions: Individualized dosing based on clinical presentation.
Clinical Use Cases
- Intubation: Not applicable to the clinical use cases of urokinase.
- Surgical Procedures: May be used during or after surgical procedures involving thromboembolic events, for example after free flap surgery where venous thrombosis occurs. Dosages vary but an example is 250,000 units over 30 minutes through a 25-gauge butterfly inserted into the recipient artery.
- Mechanical Ventilation: Not a standard indication for urokinase.
- Intensive Care Unit (ICU) Use: May be utilized in acute settings involving PE, but specific guidelines should be followed.
- Emergency Situations: May be used for acute massive PE with hemodynamic instability.
Dosage Adjustments:
Adjustments required for patients with renal or hepatic dysfunction and those with bleeding diathesis.
Side Effects
Common Side Effects
Bleeding (e.g., at the injection site, gastrointestinal, genitourinary), bruising, fever.
Rare but Serious Side Effects
Intracranial hemorrhage, allergic reactions (anaphylaxis), stroke, cholesterol embolism.
Long-Term Effects
Not applicable, as urokinase is used for acute conditions.
Adverse Drug Reactions (ADR)
Severe bleeding, including intracranial hemorrhage, requiring emergency intervention.
Contraindications
Active internal bleeding, recent stroke or surgery, severe hypertension, known hypersensitivity.
Drug Interactions
Anticoagulants (e.g., heparin, warfarin), antiplatelet drugs (e.g., aspirin, clopidogrel), and non-steroidal anti-inflammatory drugs (NSAIDs) may increase bleeding risk.
Pregnancy and Breastfeeding
Avoid using urokinase during pregnancy unless the benefits clearly outweigh the risks. Use with caution during breastfeeding and monitor the infant for bleeding complications.
Drug Profile Summary
- Mechanism of Action: Converts plasminogen to plasmin, degrading fibrin and leading to thrombolysis.
- Side Effects: Bleeding, bruising, fever, rarely intracranial hemorrhage and allergic reactions.
- Contraindications: Active bleeding, recent stroke/surgery, uncontrolled hypertension.
- Drug Interactions: Anticoagulants, antiplatelet drugs, and NSAIDs.
- Pregnancy & Breastfeeding: Use with extreme caution, assess risk/benefit.
- Dosage: Variable depending on the indication and route of administration.
- Monitoring Parameters: Coagulation studies (PT, aPTT, INR), hemoglobin, hematocrit, vital signs, signs of bleeding.
Popular Combinations
Urokinase is not typically used in combination with other thrombolytic agents. Concomitant use with heparin for anticoagulation is possible but must be done with caution and close observation of the patient for signs of bleeding.
Precautions
Closely monitor for signs of bleeding and allergic reactions. Carefully assess the patient’s medical history before initiating therapy. Assess for any contraindications to use.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Urokinase?
A: Dosage varies significantly based on the indication, patient characteristics, and the route of administration. Refer to the detailed dosage guidelines provided above.
Q2: What is the mechanism of action of Urokinase?
A: Urokinase directly converts plasminogen to plasmin, resulting in the degradation of fibrin and dissolution of thrombi.
Q3: What are the most serious side effects of Urokinase?
A: Intracranial hemorrhage, stroke, other major bleeding events.
Q4: When is Urokinase contraindicated?
A: Active internal bleeding, history of recent stroke or intracranial surgery, severe uncontrolled hypertension, and hypersensitivity to urokinase.
Q5: How should Urokinase be administered?
A: Intravenous or intra-arterial infusion or injection, depending on the clinical scenario.
Q6: How does renal impairment affect Urokinase dosage?
A: Reduce dosage and closely monitor patients with renal impairment.
Q7: Can Urokinase be used during pregnancy?
A: Only if the benefits significantly outweigh the potential risks to the fetus.
Q8: What monitoring parameters are essential during Urokinase therapy?
A: Coagulation studies (PT, aPTT, INR), hemoglobin, hematocrit, vital signs, neurologic status, signs of bleeding.
Q9: What are the potential drug interactions with Urokinase?
A: Anticoagulants (e.g., heparin, warfarin), antiplatelet agents (e.g., aspirin), and NSAIDs can increase bleeding risk when co-administered with Urokinase.
Q10: What is the role of Urokinase in central venous catheter clearance?
A: Low doses of Urokinase can be used to dissolve clots obstructing central venous catheters, restoring their patency.
