Drug information of Urokinase

Urokinase is an enzyme (protein) produced by the kidney, and found in the urine. There are two forms of urokinase which differ in molecular weight but have similar clinical effects That acts on the endogenous fibrinolytic system. It converts plasminogen to the enzyme plasmin. Plasmin degrades fibrin clots as well as fibrinogen and some other plasma proteins

Urokinase is a serine protease that activates plasminogen to an active fibrinolytic protease. The duration of action is short due to the short half life. Patients should be counselled regarding the risk of bleeding, anaphylaxis, infusion reactions, and cholesterol embolization

Absorption:Urokinase is delivered intravenously, so the bioavailability is high.

Volume of distribution:The volume of distribution of urokinase is 11.5L.

Metabolism:Because urokinase is a protein, it is expected to be metabolized by proteases to smaller proteins and amino acids.

Route of elimination:Urokinase is eliminated in the bile and urine.

Half life:Urokinase has a half life of 12.6±6.2 minutes

-Lysis of acute massive pulmonary emboli (obstruction of blood flow to a lobe or multiple segments).
-Lysis of pulmonary emboli accompanied by unstable hemodynamics 

Initial dose: 4400 international units/kg IV at a rate of 90 mL/hr over 10 minutes

Maintenance dose: 4400 international units/kg/hr IV at a rate of 15 mL for 12 hours

The use of  Urokinase  is contraindicated in patients with a history of hypersensitivity to the product . Because thrombolytic therapy increases the risk of bleeding, Urokinase is contraindicated in the situations listed below

• Active internal bleeding
• Recent (e.g., within two months) cerebrovascular accident
• Recent (e.g., within two months) intracranial or intraspinal surgery
• Recent trauma including cardiopulmonary resuscitation
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Known bleeding diatheses
• Severe uncontrolled arterial hypertension

Bleeding resulting in at least 5% decrease in hematocrit

Significant bleeding events requiring transfusion of greater than 2 units of blood

Hemorrhage, hematocrit decreased without clinically detectable hemorrhage, fatal hemorrhage, hematocrit decreased, thrombocytopenia

Hematoma, artery dissection, embolism, cholesterol embolism

Vascular pseudoaneurysm

Thromboembolism, wound hemorrhage, hypotension, flushing, cyanosis, tachycardia, hypertension, myocardial infarction

Cardiac arrest, reperfusion ventricular arrhythmias

Gastrointestinal hemorrhage, retroperitoneal hemorrhage

Gingival hemorrhage, retroperitoneal hematoma, nausea, vomiting, orolingual edema

Stroke, intracranial hemorrhage

Fatal intracranial hemorrhage, intracranial hematoma, hemiplegia

Cerebral embolism, cerebral vascular accident

Fever, chills

Substernal pain

Chest pain

Urogenital hemorrhage

Macroscopic hematuria

Microscopic hematuria

Muscle hemorrhage

Back pain

Allergic reaction

Hypersensitivity reactions, anaphylaxis

Fatal anaphylaxis

Intrahepatic hemorrhage

Transient increase in transaminases

Renal failure

Epistaxis, pulmonary embolism, dyspnea, hypoxemia, bronchospasm, recurrent pulmonary embolism

 Pulmonary edema

 Urticaria, rash, pruritus, diaphoresis

Puncture site hemorrhage, puncture site hematoma, infusion reactions

 Acidosis

- Safety and efficacy have not been established in patients younger than 18 years.

- This drug should not be mixed with other medicinal products

-If possible before you receive urokinase, tell your doctor if you have:

• a history of stroke;
• severe liver or kidney disease;
• eye problems caused by diabetes;
• bacterial endocarditis
• a blood clot of your heart;
• a recent history of stomach or intestinal bleeding;
• if you are pregnant or have had a baby within the past 10 days;
• if you have had surgery or an organ transplant within the past 10 days

-The risk of serious bleeding is increased with use of Urokinase

- Post-marketing reports of hypersensitivity reactions have included anaphylaxis ,bronchospasm, orolingual edema and urticarial

- Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents;

- Urokinase is made from human neonatal kidney cells grown in tissue culture. Products made from human source material may contain infectious agents, such as viruses, that can cause disease

-Storage requirements: Refrigerate powder at 2 to 8C 

- You may bleed more easily. Be careful and avoid injury

- Urokinase is given slowly, usually over a period of 12 hours, using a continuous infusion pump

- Hematocrit, platelet count, and activated partial thromboplastin time should be obtained prior to starting treatment

-Vital signs should be observed frequently during and following infusion

Animal studies have failed to reveal evidence of fetal harm. There are no controlled data in human pregnancy.