Urokinase


Generic Medicine Info
Indications and Dosage
Injection
Clearance of occluded catheters and shunts
Adult: Doses are administered locally into the shunt or catheter/cannula lumen only. Thrombosed arteriovenous haemodialysis shunts: 5,000-25,000 units/mL via a local forced periodic infusion (pulse spray) into both branches of the shunt. May be repeated every 30-45 minutes if necessary, up to Max of 2 hours. Max total dose: 250,000 units. Thrombosed intravascular catheters and cannulae: Via catheter lock regimen: Dissolve 5,000-25,000 units in a sufficient volume of 0.9% NaCl that will fill the lumen of the catheter/cannula. Instil the sufficient volume to fill the catheter or cannula lumen; lock or clamp off the lumen for 20-60 minutes, then aspirate the lysate. Repeat the procedure if needed. Alternatively, via infusion regimen: Using a 1,000-2,500 units/mL solution in 0.9% NaCl, infuse up to Max of 250,000 units into the catheter or cannula lumen over 90-180 minutes. Dosage recommendations may vary among individual products or between countries (refer to product-specific guidelines).

Intra-arterial
Pulmonary embolism
Adult: For acute massive cases: Initially, 15,000 units/kg as a bolus inj into the pulmonary artery; may be repeated up to 2 times at 24-hour intervals. Subsequent inj may be adjusted according to the plasma fibrinogen concentrations produced by the previous inj.

Intra-arterial
Peripheral arterial thromboembolism
Adult: In acute occlusive peripheral arterial disease with limb-threatening ischaemia: Initially, 4,000 units/minute via a local intra-arterial catheter-directed graded infusion for 2-4 hours or until antegrade flow restoration; continue infusion with 1,000-2,000 units/minute until complete lysis or up to Max of 48 hours. Alternatively, infuse 2,000 units/mL solution (dissolve 500,000 units in 250 mL 0.9% NaCl) into the clot via a catheter at 4,000 units/minute rate for 2 hours. Perform angiography; if blood flow has not resumed, advance the catheter into the occluded vessel and continue infusion at the same rate for another 2 hours. May be repeated up to 4 times if needed. When blood flow is reestablished, partially withdraw the catheter and continue infusion at a rate of 1,000 units/minute until the clot has completely lysed. Usually, a dose of 500,000 units over 8 hours is sufficient. Dosage recommendations may vary among individual products or between countries (refer to product-specific guidelines).

Intravenous
Pulmonary embolism
Adult: For acute massive cases: Initially, 4,400 units/kg via infusion in a peripheral vein over 10-20 minutes; followed by 4,400 units/kg/hour continuous infusion for 12 hours.

Intravenous
Deep vein thrombosis
Adult: For extensive acute proximal cases: Initially, 4,400 units/kg via infusion in a peripheral vein over 10-20 minutes; followed by 100,000 units/hour continuous infusion for 48-72 hours. Alternatively, initial dose of 4,400 units/kg (dissolved in 15 mL of 0.9% NaCl) infused in a peripheral vein over 10 minutes; followed by 4,400 units/kg/hour continuous infusion for 12-24 hours. Dosage recommendations may vary among individual products or between countries (refer to product-specific guidelines).
Renal Impairment
Mild to moderate: Dosage reduction may be needed. Severe: Contraindicated.
Hepatic Impairment
Mild to moderate: Dosage reduction may be needed. Severe: Contraindicated.
Reconstitution
Initially, reconstitute vials labelled as 10,000-100,000 units, 250,000 units, and 500,000 units with 2 mL, 5 mL, and 10 mL of sterile water for inj respectively. Further dilute with 0.9% NaCl to an appropriate final concentration (indication-specific). Reconstitution instructions, compatible solutions and their stability may vary among individual products or between countries (refer to detailed product guidelines).
Contraindications
Active internal or clinically relevant bleeding, aneurysm, arteriovenous malformation, intracranial neoplasm or other neoplasms with risk of haemorrhage, known coagulation disorder (e.g. haemorrhagic diathesis), severe thrombocytopenia, recent severe gastrointestinal bleeding, severe uncontrolled hypertension (systolic >200 mmHg, diastolic >100 mmHg; grade III or IV hypertensive retinopathy), sepsis, acute pancreatitis, pericarditis, acute bacterial endocarditis. Recent CVA, trauma (including CPR), thoracic surgery, or neurosurgery (within 2 months); recent major surgery until primary wound healing; recent organ biopsy, lumbar puncture, or translumbar aortography (within 10 days); recent obstetric delivery. Severe hepatic and renal impairment (unless patient is receiving renal replacement treatment).
Special Precautions
Patient with cerebrovascular disease, high likelihood of left heart thrombus (e.g. mitral stenosis with atrial fibrillation) with possible risk of cerebral embolism; cavernous pulmonary disease, diabetic haemorrhagic retinopathy or other haemorrhagic ophthalmic conditions; previous MI, haemostatic defects including those caused by severe hepatic or renal diseases; previous puncture of noncompressible vessels, recent genitourinary bleeding, or genitourinary tract diseases with potential sources of bleeding (e.g. implanted bladder catheter); prosthetic valve; septic thrombophlebitis or occluded AV cannular at seriously infected site, and any other condition in which bleeding poses a significant hazard or would cause difficult management due to location. Avoid arterial invasive procedures before and during administration. Not to be given via SC or IM inj. Concomitant use with anticoagulants, thrombolytics, or agents that inhibit platelet function. Mild to moderate hepatic and renal impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Haemorrhage, potential risk of transmission of infection, embolism including pulmonary or cholesterol embolism, infusion reactions (e.g. fever, chills, rigors). Rarely, allergic reactions (e.g. bronchospasm, rash).
Gastrointestinal disorders: Gingival bleeding, gastrointestinal or retroperitoneal haemorrhage, nausea, vomiting.
General disorders and administration site conditions: Haemorrhage from puncture sites or wounds.
Investigations: Decreased haematocrit (without clinically detectable haemorrhage), increased transaminases (transient).
Metabolism and nutrition disorders: Acidosis.
Musculoskeletal and connective tissue disorders: Muscle haemorrhage, back pain.
Nervous system disorders: Stroke, intracranial haemorrhage.
Renal and urinary disorders: Haematuria (microscopic), urogenital haemorrhage.
Respiratory, thoracic and mediastinal disorders: Epistaxis, dyspnoea, hypoxaemia.
Skin and subcutaneous tissue disorders: Cyanosis.
Vascular disorders: Thromboembolism, haematoma; artery dissection.
Potentially Fatal: Severe spontaneous bleeding including cerebral haemorrhage. Very rarely, anaphylaxis.
Monitoring Parameters
Obtain CBC including haematocrit, platelet count, thrombin time, prothrombin time, and aPTT before initiating treatment. Monitor blood pressure, pulse. Assess for signs of bleeding (e.g. haematuria, gastrointestinal or gingival bleeding).
Overdosage
Symptom: Haemorrhage. Management: Haemorrhage during therapy may be controlled with local pressure. Administer inhibitors (e.g. aprotinin, epsilon-aminocaproic acid, p-aminoethylbenzoic acid, tranexamic acid) in severe bleeding. Give human fibrinogen, factor XII, packed RBC or whole blood as necessary during serious cases.
Drug Interactions
Thrombolytic agents, anticoagulants, or agents that affect platelet function (e.g. aspirin and other NSAIDs, dipyridamole, dextrans) may further increase the risk of significant haemorrhage. Fibrinolysis may be delayed by contrast agents. May enhance the risk of angioedema with ACE inhibitors.
Action
Description: Urokinase is a thrombolytic enzyme produced by the kidney and is extracted from human urine. It converts plasminogen to plasmin, thereby degrading fibrin, fibrinogen, and other procoagulant plasma proteins.
Onset: IV: Rapid (fibrinolysis).
Duration: 12-24 hours.
Pharmacokinetics:
Metabolism: IV: Rapidly cleared from the circulation by the liver.
Excretion: Mainly via urine; faeces (small amounts). Elimination half-life: 10-20 minutes.
Storage
Store below 25°C. Protect from light.
MIMS Class
Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)
ATC Classification
B01AD04 - urokinase ; Belongs to the class of enzymes. Used in the treatment of thrombosis.
References
Anon. Urokinase. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/06/2021.

Buckingham R (ed). Urokinase. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/06/2021.

Joint Formulary Committee. Urokinase. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/06/2021.

Syner-KINASE 100,000 IU Powder for Solution for Injection/Infusion (Syner-Medica Ltd). MHRA. https://products.mhra.gov.uk. Accessed 11/08/2021.

Urokinase Medac 10,000 I.U. (medac Gesellschaft fur klinische). MHRA. https://products.mhra.gov.uk. Accessed 03/06/2021.

Urokinase Medac 100,000 I.U. (medac Gesellschaft fur klinische). MHRA. https://products.mhra.gov.uk. Accessed 03/06/2021.

Urokinase Medac 250,000 I.U. (medac Gesellschaft fur klinische). MHRA. https://products.mhra.gov.uk. Accessed 03/06/2021.

Urokinase Medac 50,000 I.U. (medac Gesellschaft fur klinische). MHRA. https://products.mhra.gov.uk. Accessed 03/06/2021.

Urokinase Medac 500,000 I.U. (medac Gesellschaft fur klinische). MHRA. https://products.mhra.gov.uk. Accessed 03/06/2021.

Urokinase. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 03/06/2021.

Disclaimer: This information is independently developed by MIMS based on Urokinase from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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