Urokinase

The fibrinolytic agent, Urokinase, acts as a dissolving agent that eliminates blood clots by activating plasminogen.

Indications Urokinase

It is possible to use Urokinase in acute thrombosis of arteries and veins, thromboembolism of pulmonary artery branches, and thrombosis of vascular shunts.

Urokinase is used for diabetic foot syndrome, which is accompanied by prolonged ulcer formation and severe leg ischemia. The drug is also prescribed in cases where surgical revascularization is impossible or ineffective, with a fibrinogen level of more than 3.5 g/liter.

[ 1 ], [ 2 ], [ 3 ], [ 4 ]

Release form

Urokinase is a powder mass for dilution with subsequent injections and infusions.

Urokinase powder is packaged in vials containing 10 thousand IU, 100 thousand IU, 500 thousand IU or 1 million IU of Urokinase.

[ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ], [ 10 ]

Pharmacodynamics

Urokinase is an enzyme substance with the active ingredient serine protease (serine in the form of an amino acid).

Urokinase has much in common with plasminogen and transforms it into plasmin by hydrolysis of the arginine-valine linkage. Fibrin thrombi are able to dissolve under the action of the thrombolytic property of plasmin protease.

The active state of plasma induced by Urokinase promotes a dose-dependent decrease in the amount of plasminogen and fibrinogen, and also increases the content of fibrin and fibrinogen hydrolysis products. Hydrolysis products affect the decrease in blood coagulability and enhance the effect of heparin. Such properties are manifested within 24 hours after the administration of Urokinase.

Induced transformation of plasminogen into plasmin can be inhibited by epsilon-aminocaproic, tranexamic and aminobenzoic acids. These inhibitors do not have a potentiating effect on the anticoagulant property of fibrin and fibrinogen in the circulation.

[ 11 ], [ 12 ]

Pharmacokinetics

Urokinase is given into arteries or veins by injection or infusion.

In animal studies, it was found that Urokinase is degraded by enzymatic substances. The liver plays a major role in the biological transformation of Urokinase. Inactive metabolites are excreted in feces and urine.

The half-life of Urokinase is estimated to be 9-16 minutes. Clinical duration may depend on the period of exposure to active plasmin.

[ 13 ], [ 14 ], [ 15 ], [ 16 ], [ 17 ], [ 18 ]

Dosing and administration

Urokinase solution can be administered intravenously by injection or infusion, either as a single drug or as part of a combination treatment with heparin.

The dosage of Urokinase is determined individually, under the control of blood clotting parameters.

• In case of deep vein thrombosis:
  • the initial dose of the drug Urokinase is 4400 IU per kg of weight, for patients from the risk group 150 thousand IU over 15 minutes;
  • maintenance dose of 100 thousand IU per hour, and for patients from the risk group - from 40 to 60 thousand IU for 2-3 days;
  • After three days the dosage can be revised.
• For severe pulmonary embolism:
  • the initial dose of the drug Urokinase is 4400 IU per kg of weight over 15 minutes;
  • maintenance dose of Urokinase 4400 IU/kg body weight/hour for 12 hours;
  • If the effectiveness is insufficient, the dosage can be increased after 24 hours.
• In case of obstruction of peripheral vessels:
  • 240 thousand IU per hour is administered as an infusion using an intra-arterial catheter for 2-4 hours, or until blood flow is clear, after which they switch to a regime of 1-2 thousand IU per minute;
  • The infusion is completed at the end of thrombolysis, or two days after the start of the infusion.
• In case of fibrin blockage of hemodialysis shunts:
  • Urokinase solution 5-25 thousand IU per ml is injected into both branches of the vascular shunt;
  • if necessary, the infusion is repeated after 35-40 minutes;
  • The total period of use of Urokinase should not exceed 120 minutes.

Immediately before use, Urokinase powder is diluted in water for injection according to the following scheme:

• for Urokinase 10 thousand IU, 50 thousand IU or 100 thousand IU, 2 ml of dissolving liquid is required;
• For Urokinase 500 thousand IU, 10 ml of dissolving liquid is required.

Next, the drug is diluted to the desired consistency with saline or 5-10% glucose solution. Urokinase is administered immediately after dilution.

[ 30 ], [ 31 ], [ 32 ]

Use Urokinase during pregnancy

There is no data on the passage of Urokinase into breast milk, as well as information on the possibility of using the fibrinolytic during pregnancy. The likelihood of bleeding, the risk of premature labor and the occurrence of other complications, such as premature placental abruption, cannot be ignored.

It has been proven that Urokinase partially crosses the placental barrier.

Based on the available information, the use of Urokinase during pregnancy is not recommended, as well as during the month after the birth of the child.

Contraindications

Among the absolute contraindications to the use of Urokinase are:

• recent bleeding (especially those related to cerebrovascular events);
• stroke, vascular ruptures that occurred within the last eight weeks;
• recent surgery, as well as the condition preceding the primary healing of the wound surface;
• weak activity of the blood coagulation system, tendency to bleeding (types of hemorrhagic diathesis and fibrinolysis);
• severe forms of hypertension, retinopathy associated with high blood pressure;
• severe pathologies of the liver and renal filtration system;
• increased likelihood of gastrointestinal bleeding (peptic ulcer, tumor processes in the digestive system, etc.);
• increased risk of bleeding in the presence of kidney stones or tumors of the urinary system;
• tuberculosis, hemoptysis;
• aneurysm dissection;
• exacerbation of pancreatitis;
• endocarditis;
• microbial sepsis, septic vascular occlusion;
• the first month after the birth of a child, spontaneous or medical abortion, or after a threatened termination of pregnancy;
• bleeding carcinoma;
• the first month after lumbar aortography;
• the first 8-10 days after uncomplicated spinal puncture.

Relative contraindications to the use of Urokinase are:

• recent resuscitation measures, mitral valve pathologies and atrial fibrillation;
• prolongation of thromboplastin period, thrombocytopenia;
• pregnancy period;
• violation of the integrity of arterial vessels

[ 19 ], [ 20 ], [ 21 ]

Side effects Urokinase

The most common side effects after the administration of Urokinase are:

• microbleeding;
• bleeding from damaged vessels;
• hematomas.

A number of patients experienced severe bleeding into the digestive organs, liver, as well as intracerebral and retroperitoneal hemorrhages during treatment with Urokinase.

Often, a transient increase in transaminase levels and a decrease in hematocrit levels without obvious bleeding are recorded.

Embolism may develop.

In rare cases, an allergy develops, which manifests itself as reddening of the skin, difficulty breathing, and a drop in blood pressure.

[ 22 ], [ 23 ], [ 24 ], [ 25 ], [ 26 ], [ 27 ], [ 28 ], [ 29 ]

Overdose

The main symptom of Urokinase overdose is bleeding, which must be stopped by compression. If the compression method does not stop the bleeding, then the Urokinase infusion is stopped and hemostatic agents are administered.

The initial dose of Aprotinin (an antienzyme drug, an inhibitor of the fibrinolytic enzyme plasmin) should be 500 thousand – 1 million IU per hour intravenously, with a subsequent maintenance dose of 50-100 thousand IU per hour until complete hemostatic stabilization.

If profuse bleeding occurs, Urokinase infusion is stopped immediately. Hemostatic treatment is started with infusion of concentrated fibrinogen and other blood products (if required).

Treatment for overdose of Urokinase should be carried out under the supervision of a physician experienced in transfusion therapy and hemostasis.

[ 33 ], [ 34 ], [ 35 ]

Interactions with other drugs

The risk of bleeding increases with the combined administration of Urokinase:

• with drugs that inhibit blood clotting (medicines based on heparin or coumarin);
• with drugs that affect the quality and quantity of platelets (aspirin, allopurinol, phenylbutazone, tetracycline, sulfonamides, antirheumatic drugs, cytostatics, indomethacin, clofibric acid, dipyridamole, etc.);
• with medications that inhibit the properties of Urokinase (antifibrinolytics).

[ 36 ], [ 37 ], [ 38 ], [ 39 ], [ 40 ]

Storage conditions

Store Urokinase in a place inaccessible to children, away from heating devices, in rooms with temperatures up to +25°C.

[ 41 ]

Shelf life

Urokinase can be stored in sealed form for up to 3 years.

The prepared solution should be used immediately. If the Urokinase solution was diluted under aseptic conditions, it can be stored for a maximum of 8 hours.

[ 42 ], [ 43 ], [ 44 ], [ 45 ]