Generic Name: Urokinase
Class: Thrombolytic Agents
CAS Number: 9039-53-6
Introduction
Thrombolytic agent; plasminogen activator isolated from human neonatal kidney cell cultures.111 122 125 136 137 153 155
Uses for Kinlytic
PE
Lysis of acute massive PE (obstruction or substantial filling defects of ≥2 lobar pulmonary arteries or multiple segments of lungs).111 117 120 132 133 134 136 140 155
Lysis of PE accompanied by unstable hemodynamics (i.e., failure to maintain BP without supportive measures).111 117 120 132 133 134 136 140 155
Generally reserve IV thrombolytic therapy for those with acute massive PE accompanied by unstable hemodynamics (e.g., shock) who do not have major contraindications because of bleeding risk117 120 121 122 132 133 140 156 or in those with stable hemodynamics with other poor prognostic factors (e.g., marked dyspnea, anxiety, and low oxygen saturation; elevated troponin concentrations indicative of right ventricular microinfarction; echocardiographic evidence of right ventricular dysfunction; right ventricular enlargement on a chest computed-tomography scan).133 135 138 156
The American College of Chest Physicians (ACCP) suggests that thrombolytic agents with a short infusion time (e.g., 2 hours for alteplase) are preferred over those with a longer infusion time (e.g., 12 hours for urokinase)156 because of increased bleeding risk with prolonged infusion.136 143 146 Urokinase also has been effective and safe when given as a 2-hour IV infusion† for PE.132 134 135 148 (See PE under Dosage.)
Confirm diagnosis of PE objectively by pulmonary angiography or lung scan (e.g., computed tomography with IV contrast).111 119 122 133 152 155
Perform a rapid risk assessment to determine if thrombolytic therapy is appropriate; irreversible cardiogenic shock may occur if therapy is delayed in patients with evidence of hemodynamic compromise.156
If thrombolytic therapy fails or is contraindicated in patients with massive PE and hemodynamic instability, pulmonary embolectomy may be required.117 120 156
DVT
Has been used in selected patients for treatment of DVT† (e.g., popliteal or posterior tibial vein).117 140
ACCP suggests thrombolytic therapy be reserved for use in selected patients at low risk of bleeding who have extensive acute proximal DVT† (e.g., iliofemoral DVT) with symptom onset of <14 days, life expectancy of ≥1 year, and good functional status.156 ACCP also suggests thrombolytic therapy as initial treatment in patients with severe upper extremity DVT† who have recent symptom onset and low risk of bleeding.156
Coronary Artery Thrombosis and MI
Has been used for lysis of coronary artery thrombi in selected patients with acute evolving transmural MI†, in conjunction with heparin and/or platelet-aggregation inhibitors (e.g., aspirin).101 102 104 105 106 107 151 (See Adjunctive Anticoagulant Therapy under Dosage and Administration.)
Clinical evaluation of IV urokinase therapy in patients with MI is limited; offers no clinical advantage over other currently available thrombolytic agents (e.g., alteplase, reteplase, tenecteplase).102 127 154
Arterial Thrombosis and Embolism
Used intra-arterially for lysis of arterial occlusions in peripheral vessels and bypass grafts† in selected patients with acute (<14 days old) thromboembolic arterial ischemia.118 ACCP suggests that such therapy should be used in patients who have a low risk for development of myonecrosis and ischemic nerve damage in the affected extremity.118
Occluded IV Catheters
Restoration of patency to IV catheters†, including central venous catheters, obstructed by clotted blood or fibrin.112 116
Thromboembolism Associated with Prosthetic Heart Valves
Has been used in a limited number of patients for treatment of prosthetic heart-valve thrombosis†.158
ACCP suggests thrombolytic therapy for patients with right-sided prosthetic valve thrombosis and NYHA functional class III or IV heart failure and in patients with left-sided prosthetic valve thrombosis and NYHA functional class I–IV with small thrombi (<0.8 cm2).158 In patients with a large (≥0.8 cm2) left-sided prosthetic valve thrombus, ACCP suggests thrombolytic therapy if emergency surgery is not available or considered high risk.158
Kinlytic Dosage and Administration
General
PE
Initiate therapy as soon as possible (preferably within several days) after onset of symptoms of PE to achieve greatest clinical benefit;111 131 134 140 155 thrombolysis is still beneficial ≤14 days following symptom onset.124 131 134 135 136
Determine aPTT, hematocrit, and platelet count to assess patient's hemostatic status (e.g., determine if a serious hemostatic defect exists) prior to initiating urokinase.111 155 However, results of coagulation tests and measures of thrombolytic activity do not reliably predict either drug efficacy or risk of bleeding.111 125 152 155
DVT
Adjunctive Anticoagulant Therapy for PE
Heparin should not be infused concurrently with urokinase in patients with PE.117 152 In patients who have received heparin, generally allow aPTT to diminish to <2 times the control value before urokinase therapy is initiated.111 155
To minimize risk of rethrombosis and recurrent PE following thrombolytic therapy,120 122 institute anticoagulant therapy (e.g., heparin) when the aPTT has decreased to <2 times the control value.111 136 155 Follow heparin therapy with oral anticoagulant therapy.111 136 155
Adjunctive Anticoagulant Therapy for Coronary Artery Thrombosis and MI
In patients with acute MI† who are at high risk for systemic emboli (e.g., large or anterior acute MI, atrial fibrillation, history of embolism, known left ventricular thrombus),151 IV heparin sodium, usually 5000 units by rapid IV injection followed by a continuous IV infusion, has been administered concomitantly with or immediately following urokinase infusion.104 105 106 107
Administration
For drug compatibility information, see Compatibility under Stability.
Administer by IV infusion via a controlled-infusion device only.111 155
Also has been administered by intracoronary infusion†, intra-arterial infusion†, or intracatheter instillation†.101 102 112 116 118 154
IV Administration
For treatment of PE, administer by IV infusion via a constant infusion pump capable of delivering a total volume of 195 mL.111 155
Reconstitution
Reconstitute vial containing 250,000 units of urokinase by adding 5 mL of sterile water for injection without preservatives to provide a concentration of 50,000 units/mL.111 155 Gently roll and tilt vial until lyophilized powder dissolves to produce a clear or slightly straw-colored solution.155 Avoid shaking to minimize formation of filaments.111 155 Presence of such filaments does not indicate any decrease in potency;111 155 such solutions may be filtered through ≤0.45-mcm cellulose membrane filter.111 155
Dilution
Following reconstitution, dilute further with 0.9% sodium chloride or 5% dextrose injection to yield a final infusion volume of 195 mL.111 155
Rate of Administration
PE: Infuse at 90 mL/hour over 10 minutes (loading dose), then 15 mL/hour for 12 hours (maintenance dosage).111 117 155 To ensure delivery of entire dose, flush IV tubing with a volume of compatible diluent equal to that of tubing volume at a rate of 15 mL/hour.111 155
PE: Has also been administered as a 2-hour IV infusion†.132 134 135 148 (See PE under Dosage.)
Coronary artery thrombosis and MI†: Administer 50% or 100% of the dose over 5 minutes as a rapid IV injection and the remainder, if any, as a continuous infusion over 45–90 minutes.104 105 106 107
Dosage
Dosage of urokinase is expressed in international units (units);111 155 biologic activity determined using an in vitro lysis assay.a
Adults
PE
IV
Loading dose: Initially, 4400 units/kg over 10 minutes recommended by manufacturer.111 117 155
Maintenance dosage: 4400 units/kg per hour for 12 hours recommended by manufacturer.111 155 To ensure delivery of entire dose, flush IV tubing with a volume of 0.9% sodium chloride or 5% dextrose injection equal to that of tubing volume.111 155
Repeat administration as necessary.155
Has also been administered in a dosage of 3 million units over 2 hours†, with initial 1 million units infused over 10 minutes.132 134 135 148
Coronary Artery Thrombosis and MI†
IV
2–3 million units has been administered over 45–90 minutes, with 50% or 100% of the dose given as an initial rapid IV injection (e.g., over 5 minutes) and the remainder, if any, as a continuous infusion.104 105 106 107
Cautions for Kinlytic
Contraindications
Active internal bleeding.111 152 155
Recent (≤2 months) cerebrovascular accident.111 152 155
Recent trauma, including CPR.111 155
Known bleeding diathesis.111 155
Severe uncontrolled arterial hypertension.111 155
Intracranial neoplasms.111 152 155
Intracranial vascular disease (i.e., aneurysm, arteriovenous malformation).111 152 155
Recent (≤2 months) intracranial or intraspinal surgery.111 155
Known hypersensitivity to urokinase or any ingredient in the formulation.111 155
Warnings/Precautions
Warnings
Effects on Hemostasis
Possible bleeding and hemorrhagic complications, including intracranial hemorrhage and other major bleeding complications.111 120 126 133 134 137 155 May be more common in geriatric patients, patients with renal or hepatic dysfunction, and those receiving intense or prolonged antithrombotic therapy.133 136
Weigh increased risks of therapy against anticipated benefits in patients with recent (≤10 days) major surgery, obstetric delivery, organ biopsy, previous puncture of noncompressible vessels, cerebrovascular disease (other than contraindicated conditions), hemostatic defects (e.g., secondary to severe hepatic or renal disease), recent (≤10 days) serious GI bleeding, high likelihood of left heart thrombus (e.g., mitral stenosis with atrial fibrillation), pregnancy, diabetic hemorrhagic retinopathy, or subacute bacterial endocarditis.111 155 Weigh risks against benefits in patients with any condition in which bleeding constitutes a substantial hazard or would be especially difficult to manage because of its location.111 155
Minimize risk of bleeding by carefully selecting patients and monitoring all potential bleeding sites (e.g., sites of all cutdowns; arterial, venous, and other needle punctures; catheter insertion sites).111 134 155 Avoid IM injections and nonessential handling of patient.111 134 155 Perform invasive venous procedures as carefully and as infrequently as possible.111 134 136 155 Avoid arterial invasive procedures;a use upper extremity artery (radial or brachial) if arterial puncture is essential.111 155 Apply pressure to puncture site for ≥30 minutes, apply pressure dressing, and check site frequently for evidence of bleeding.111 155
Severe and fatal spontaneous (e.g., cerebral, retroperitoneal) bleeding has occurred.111 120 126 133 134 137 155
Internal bleeding with urokinase may be more difficult to control than that which occurs with conventional anticoagulant therapy.111 155 Possible lysis of fibrin deposits that provide hemostasis (e.g., at sites of needle punctures, cuts); bleeding from such sites may result.125 126 134
If serious spontaneous bleeding occurs, immediately discontinue urokinase therapy.111 133 134 152 155 Initiate appropriate hemostatic therapy as needed (e.g., plasma volume expanders other than dextrans, packed RBCs, cryoprecipitate, fresh frozen plasma) to replace blood volume deficits and/or reverse bleeding tendency.111 134 152 155 a
Concomitant Antithrombotic Therapy
Concomitant use with other thrombolytic agents, anticoagulants, or agents inhibiting platelet function may increase risk of serious bleeding.111 155 (See Specific Drugs under Interactions.)
Do not use aspirin and other NSAIAs that inhibit platelet function for treatment of fever (e.g., fever associated with infusion reactions).111 (See Sensitivity Reactions under Cautions.)
Cholesterol Embolization
Cholesterol embolization and associated serious complications reported rarely in patients receiving thrombolytic therapy, including urokinase.111 155 Possibly fatal cholesterol embolization associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant agents.111 155 Clinical features of cholesterol embolism include livedo reticularis, “purple toe” syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, MI, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.111 155
Risk of Transmissible Agents in Serum-derived Preparations
Potential vehicle for transmission of human viruses (e.g., HIV, hepatitis B virus [HBV], hepatitis C virus [HCV], human T-lymphotropic virus [HTLV], cytomegalovirus [CMV], human papilloma virus [HPV], Epstein-Barr virus [EBV]) or other infectious agents.111 155
Despite application of a number of viral elimination/reduction steps (e.g., heat treatment in solution, purification, screening for certain viruses) to prevent transmission of infectious agents, risk of transmission still remains.111 155
Report all infections thought possibly to have been transmitted by urokinase to the manufacturer at 866-634-6279.111 155
Risk of Creutzfeldt-Jakob Disease
Formulation contains 5% albumin.111 155 May carry a remote risk of transmitting causative agent of Creutzfeldt-Jakob disease (CJD).111 155 Currently, no evidence of transmission of CJD via albumin component.111 155
Sensitivity Reactions
Possible anaphylaxis; rare fatalities.111 134 155 Other allergic-type reactions (e.g., orolingual edema, bronchospasm, urticaria) reported.111 134 155
Acute infusion reactions, including fever, chills or shaking chills (rigors), hypotension, nausea, vomiting, hypoxia, cyanosis, dyspnea, tachycardia, hypertension, acidosis, and/or back pain, may occur; such reactions generally begin ≤1 hour after treatment initiation.111 134 155
If infusion reactions occur, immediately discontinue therapy, monitor patient closely, and institute appropriate therapy (e.g., IV antihistamines, adrenergic agents, corticosteroids).111 155 (See Concomitant Antithrombotic Therapy under Cautions.)
Specific Populations
Pregnancy
Category B.111 155
Lactation
Not known whether urokinase is distributed into milk.111 155 Use caution.111 155
Pediatric Use
Safety and efficacy of urokinase not established.111 155
Thrombolytic therapy generally not recommended for treatment of venous thromboembolism in neonates and children unless vessel occlusion is severe and causes organ dysfunction or limb ischemia.157 If thrombolysis is required, ACCP states that alteplase is the drug of choice in pediatric patients because of greater fibrin specificity, lower immunogenicity, and more effective clot lysis in vitro compared with urokinase.157
Geriatric Use
Insufficient experience in patients ≥65 years of age to determine whether such patients respond differently than younger adults.111 155 Use with caution.111 155
Common Adverse Effects
Bleeding.111 155
Interactions for Kinlytic
Specific Drugs
Drug
|
Interaction
|
Comments
|
|---|
Dipyridamole
|
Increased risk of hemorrhage111 155
|
Monitor carefully for evidence of bleeding111 155
|
GP IIb/IIIa inhibitors
|
Increased risk of hemorrhage111 155
|
Monitor carefully for evidence of bleeding111 155
|
Heparin
|
Increased risk of hemorrhage111 155
|
Concurrent use not recommended in patients with PE111 117 152 (see Adjunctive Anticoagulant Therapy under Dosage and Administration)
If used, monitor carefully for evidence of bleeding111 155
|
NSAIAs (e.g., aspirin)
|
Increased risk of hemorrhage111 155
|
Do not use for treatment of fever (e.g., infusion reactions)111 155
If used, monitor carefully for evidence of bleeding111 155
|
Thrombolytic agents
|
Increased risk of hemorrhage111 155
|
Monitor carefully for evidence of bleeding111 155
|
Kinlytic Pharmacokinetics
Absorption
Onset
PE: Clinical improvement and measurable hemodynamic changes may occur within a few hours but may not be observed until 6–8 hours after treatment initiation.a
Duration
PE: Fibrinolytic effects usually disappear within a few hours.111 155 Decreased plasma concentrations of fibrinogen and plasminogen and increased circulating concentrations of degradation products of fibrinogen and fibrin may persist for 12–24 hours after discontinuance of IV infusion.111 155
Elimination
Elimination Route
Rapidly cleared by liver.111 155 Small amount of urokinase eliminated in urine and feces via biliary excretion.111 122 155
Half-life
12.6 minutes.111 155
Special Populations
Pharmacokinetics not characterized in patients with hepatic impairment.111 155 Endogenous urokinase-type plasminogen activator plasma concentrations are elevated twofold to fourfold in patients with moderate to severe cirrhosis; hepatic impairment might be expected to reduce clearance of urokinase.111 155
Stability
Storage
Parenteral
Powder for Injection
Refrigerate at 2–8°C.111 155
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Drug Compatibility
Do not mix with other drugs for IV infusion.111 155
ActionsActions
Directly activates conversion of fibrin-bound and circulating plasminogen to proteolytic enzyme plasmin.111 136 144 145 153 155 Plasmin degrades fibrin, fibrinogen and other clotting factors, and other plasma procoagulant proteins.111 144 145 153 155
Decreases plasma concentrations of fibrinogen and plasminogen and increases circulating concentrations of degradation products of fibrinogen and fibrin.111 155
Exhibits less fibrin selectivity than alteplase, reteplase, and tenecteplase.117 152 153 151 May lyse fibrin deposits that provide hemostasis (e.g., at sites of needle punctures, cuts); bleeding from such sites may result.117 125 126 134
Degradation of fibrinogen and fibrin and other clotting factors induces anticoagulant effect.a 151 152 153
Advice to Patients
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.111
Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.111
Importance of advising patients of other important precautionary information.111 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Urokinase powder for injection, formerly marketed as Abbokinase (Abbott Laboratories), has been rebranded as Kinlytic after completion of stability studies on existing inventory to extend the expiration dating.154 Urokinase injection may continue to be available from some suppliers as Abbokinase until that inventory is exhausted.154 Hospitals should deplete their current stocks of Abbokinase before using Kinlytic.154
Urokinase
Routes
|
Dosage Forms
|
Strengths
|
Brand Names
|
Manufacturer
|
|---|
Parenteral
|
For injection, IV infusion
|
250,000 units
|
Abbokinase (heat-treated, wet method)
|
ImaRX
|
|
|
|
Kinlytic (heat-treated, wet method)
|
ImaRX
|
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions December 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
Only references cited for selected revisions after 1984 are available electronically.
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154. ImaRX Therapeutics, Tucson, AZ: Personal communication.
155. ImaRX Therapeutics Inc. Kinlytic (urokinase) for injection prescribing information. Tucson, AZ; 2007 June.
156. Kearon C, Kahn SR, Agnelli G et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest. 2008; 133 (Suppl): 454S-545S. [PubMed 18574272]
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