Urokinase

What is Urokinase?

• Urokinase (kinlytic) is a thrombolytic agent obtained from human neonatal kidney cells grown in tissue culture.
• It is an enzyme that is made in the kidney and found in the urine.
• Urokinase consists of an A chain of 2,000 daltons linked by a sulfhydryl bond to a B chain of 30,400 daltons.
• Kinlytic is produced from human neonatal kidney cells.
• No fetal tissue is used in the production of Kinlytic.
• Kidney donations are obtained exclusively in the United States from neonates (birth to 28 days) for whom death has not been attributed to infectious causes and that have exhibited no evidence of an infectious disease based in part, on an examination of the maternal and neonatal donor medical records.

PDB 1fv9 EBI

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What are the uses of this medicine?

Urokinase (kinlytic) is used in adults:

• For the lysis of acute massive pulmonary emboli, defined as obstruction of blood flow to a lobe or multiple segments.
• For the lysis of pulmonary emboli accompanied by unstable hemodynamics, i.e., failure to maintain blood pressure without supportive measures.

How does this medicine work?

• 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.
• Kinlytic is the low molecular weight form.
• Kinlytic 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.
• Intravenous infusion of Kinlytic™ in doses recommended for lysis of pulmonary embolism is followed by increased fibrinolytic activity in the circulation.
• This effect disappears within a few hours after discontinuation, but a decrease in plasma levels of fibrinogen and plasminogen and an increase in the amount of circulating fibrin and fibrinogen degradation products may persist for 12-24 hours.
• There is a lack of correlation between embolus resolution and changes in coagulation and fibrinolytic assay results.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• a history of hypersensitivity to the product.
• 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.

What drug interactions can this medicine cause?

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Be sure to mention any of the following:

• Anticoagulants and agents that alter platelet function (such as aspirin, other non-steroidal anti-inflammatory agents, dipyridamole, and GP IIb/IIIa inhibitors).

Is this medicine FDA approved?

• Yes,It was FDA approved.

How should this medicine be used?

• Kinlytic treatment should be instituted soon after onset of pulmonary embolism.

Recommended dosage:

• A loading dose of 4,400 international units per kilogram of Kinlytic™ is given at a rate of 90 mL per hour over a period of 10 minutes.
• This is followed by a continuous infusion of 4,400 international units per kilogram per hour at a rate of 15 mL for 12 hours.
• Administration of Kinlytic™ may be repeated as necessary.

Administration:

• Kinlytic contains no preservatives.
• Do not reconstitute until immediately before use.
• Any unused portion of the reconstituted material should be discarded.
• Reconstitute Kinlytic by aseptically adding 5 mL of Sterile Water for Injection, USP, without preservatives, to the vial.
• DO NOT USE Bacteriostatic Water for Injection, USP.
• After reconstitution, the drug product will contain 50,000 international units per milliliter.
• After reconstituting, visually inspect each vial of Kinlytic™ for discoloration and for the presence of particulate material.
• Kinlytic™ is administered using a constant infusion pump that is capable of delivering a total volume of 195 mL.
• After infusing Kinlytic, anticoagulation treatment is recommended to prevent recurrent thrombosis.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As a sterile lyophilized preparation
• Each vial contains 250,000 international units urokinase.

This medicine is available in fallowing brand namesː

• Kinlytic

What side effects can this medication cause?

The most common side effects of this medicine include:

• bleeding

Less common,but serious side effects may include:

• fatal hemorrhage
• anaphylaxis

Allergic Reactions:

• bronchospasm, orolingual edema, urticaria, skin rash, and pruritus

• Infusion reaction symptoms include hypoxia, cyanosis, dyspnea, tachycardia, hypotension, hypertension, acidosis, fever and/or chills/rigors, back pain, vomiting, and nausea.

Additional side effects may include:

• myocardial infarction, recurrent pulmonary embolism, hemiplegia, stroke, decreased hematocrit, substernal pain, thrombocytopenia, and diaphoresis.

What special precautions should I follow?

• The risk of serious bleeding is increased with use of Kinlytic. Concurrent administration of Kinlytic™ with other thrombolytic agents, anticoagulants, or agents inhibiting platelet function may further increase the risk of serious bleeding.
• Hypersensitivity reactions including anaphylaxis (with rare reports of fatal anaphylaxis), bronchospasm, orolingual edema and urticaria have been reported. Patients who exhibit reactions should be closely monitored and appropriate therapy instituted. Infusion reactions generally respond to discontinuation of the infusion and/or administration of intravenous antihistamines, corticosteroids, or adrenergic agents.
• Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents.
• Kinlytic 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. The risk that Kinlytic will transmit an infectious agent has been reduced by screening donors for prior exposure to certain viruses, by testing donors for the presence of certain current virus infections, by testing for certain viruses during manufacturing, and by inactivating and/or removing certain viruses during manufacturing.
• This product is formulated in 5% albumin, a derivative of human blood. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote.
• Kinlytic should be used in hospitals where the recommended diagnostic and monitoring techniques are available.
• Before beginning thrombolytic therapy, obtain a hematocrit, platelet count, and an activated partial thromboplastin time (aPTT).
• It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Kinlytic™ is administered to a nursing woman.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• Bleeding, as well as deaths due to hemorrhage, have been observed in some reports of overdose

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Pregnancy Category B.
• There are, however, no adequate and well-controlled studies in pregnant women.
• Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Can this medicine be used in children?

• Safety and effectiveness in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• UROKINASE

Inactive ingredients:

• Mannitol
• albumin (human)
• Sodium chloride

Who manufactures and distributes this medicine?

• ImaRx Therapeutics, Inc. Tucson Arizona, USA.

What should I know about storage and disposal of this medication?

• Refrigerate Kinlytic powder at 2° to 8°C (36° to 46°F).

• Dailymed label info on Urokinase
• FDA Urokinase

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