Urokinase - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Fibrinolytics

Included in the formulation

Urokinase medak

lyophilizate d / infusion

medac GmbH Germany

АТХ:

B.01.A.D.04 Urokinase

Pharmacodynamics:

Activation of plasminogen, conversion of plasminogen to plasmin, destruction of fibrin, fibrinogen, coagulation factors V and VIII.

Pharmacokinetics:

Biotransformation occurs in the liver. Half-life20 minutes. Elimination of small fragments of complexes by the kidneys.

Indications:

Acute forms of arterial and venous thrombosis and thromboembolism of various locations (including deep vein thrombosis, pulmonary embolism, peripheral arterial thrombosis, myocardial infarction, hemorrhage in the anterior chamber of the eye, vitreous humor). Thrombosis of hemodialysis arterio-venous shunts, intravenous cannula.

ICD-10

IX.I80-I89.I82.9 Embolism and thrombosis of unspecified vein

IX.I80-I89.I82.8 Embolism and thrombosis of other specified veins

IX.I80-I89.I82 Embolism and thrombosis of other veins

IX.I70-I79.I74 Embolism and thrombosis of the arteries

IX.I26-I28.I26 Pulmonary embolism

IX.I20-I25.I21 Acute myocardial infarction

Contraindications:

Hypersensitivity. Bleeding (which took place recently, continued and increased risk of its development); the first 72 hours after surgery (especially neurosurgical), hypocoagulation (especially on the background of severe hepatic and / or renal failure),10 days after biopsy and after childbirth, recent arterial puncture inaccessible to local compression, erosive-ulcerative lesions of the gastrointestinal tract, stomach cancer, cerebral thrombosis, hypertension, recent cerebral trauma, hematoma, brain tumors, acute pulmonary edema, bleeding tumor, diabetic hemorrhagic retinopathy, vertebral or carotid artery thrombosis, acute and subacute bacterial endocarditis, mitral stenosis, atrial fibrillation, I trimester of pregnancy.

Carefully:

Children and the elderly, liver and kidney disease, pregnancy and lactation.

Pregnancy and lactation:

The category of recommendations for the FDA is B.

Controlled studies in humans are not conducted. Possible development of fetal side effects observed in adults. It is suggested that the administration of thrombolytic agents during the first 18 weeks of pregnancy may increase the risk of premature placenta separation, since the latter is attached to the uterus mainly with fibrin, but such effects were not noted in the presence of urokinase in the I-II trimester of pregnancy in humans. Do not use within 4 weeks after delivery.There is no information on the penetration into breast milk. Due to the excretion of many drugs with milk, thrombolytic agents should be used with lactating women with caution.

Dosing and Administration:

Intravenously drip or jet.

The required dose is selected individually. Therefore, the following diagrams should be used as a general guide for dose selection. Depending on the clinical picture, the dose may be increased. As a rule, an increase in thrombin time 3-5 times relative to the norm is considered optimal to achieve an adequate effect. Also, standard blood coagulability parameters should be monitored in order to select the dosage based on them.

Deep vein thrombosis. Initial dose - 4400 IU / kg, for patients at high risk - 150,000 IU for 10-20 minutes; maintenance dose - 100,000 IU / h, for patients at high risk - 40000-60000 IU for 2-3 days.

If the desired effect can not be achieved after 72 hours, the dose can be increased individually in each case.

Severe pulmonary embolism. Initial dose - 4400 IU / kg for 10-20 minutes; maintenance dose - 4400 IU / kg / h for 12 hours.

If the desired effect can not be achieved after 24 hours, the dose can be increased individually in each case.

Occlusion of peripheral vessels: 4000 IU / min (240000 IU / h) is infused into the intraarterial catheter in the first 2-4 hours or until the anterograde blood flow (patency) is restored, then - 1000-2000 IU / min. Infusion should be discontinued after the completion of the thrombus lysis, if the arteriography shows no further progress, or after 48 hours after the start of the infusion.

Blocking fibrin clots of hemodialysis shunts. For use in lysis of thrombi in arteriovenous shunts, the drug is dissolved in 2-3 ml of physiological solution to obtain a solution with a concentration of 5000 to 25000 IU / ml. The solution is introduced into both branches of the arteriovenous shunt. If necessary, the administration is repeated after 30-45 minutes. The total time of application should not exceed 2 hours.

To prevent the re-formation of clots after the application of urokinase, treatment with heparin and oral anticoagulants in usual doses with the control of standard coagulogram parameters should be started.

Preparation of the drug solution

Before use, the preparation should be dissolved in water for injection in accordance with the following scheme: 10000 IU bottle use 2 ml of solvent; 50000 IU - 2 ml of solvent; 100,000 IU - 2 ml of solvent; 500,000 IU - 10 ml of solvent. After that, it can be diluted to the required concentration of 0.9% solution of sodium chloride or 5 or 10% glucose solution.

The solution should be used immediately after preparation.

Side effects:

From the side blood coagulation system: hemorrhage in the field of perfusion (especially with its duration of more than 48 hours), bleeding (gingival, intestinal), rarely - purpura, embolia fragments of the lysed primary thrombus, a decrease in hematocrit.

Very rarely: nonspecific reactions to protein-shock, increased activity of hepatic transaminases, nausea, vomiting, decreased appetite, fever, chills, headache, lethargy.

Overdose:

Symptoms: bleeding.

Treatment: aminocaproic acid, human fibrinogen, whole blood transfusion.

Interaction:

When used simultaneously with anticoagulants, drugs that have antiaggregant activity (including acetylsalicylic acid, indomethacin, phenylbutazone), the risk of bleeding increases.

An antagonist of urokinase is epsilon-aminocaproic acid.

Special instructions:

With caution use urokinase in elderly patients, with suspected exfoliating aortic aneurysm, in the case of cardiopulmonary resuscitation.

Systemic administration of urokinase requires hematological control.

Against the background of the use of urokinase with an increase in body temperature, the use of acetylsalicylic acid is not recommended, in such cases it is preferable paracetamol.

The safety and efficacy of urokinase in children have not been studied.

Instructions

Urokinase (Urokinasum)