UROKINASI 100.000 IU/2 ML Powder and solvent for intravenous infusion solution

Зміст інструкції

1. UROKINASI PFIZER 100,000 U.I./2 ml powder and solvent for injectable solution
   1. What is Urokinasi Pfizer and what is it used for
   2. What you need to know before using Urokinase Pfizer
   3. How to use Urokinasi Pfizer
   4. Possible side effects
   5. How to store Urokinasi Pfizer
   6. Contents of the pack and other information

UROKINASI PFIZER 100,000 U.I./2 ml powder and solvent for injectable solution

Generic medicine

Read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

• 1. What Urokinasi Pfizer is and what it is used for
• 2. What you need to know before using Urokinasi Pfizer
• 3. How to use Urokinasi Pfizer
• 4. Possible side effects
• 5. How to store Urokinasi Pfizer
• 6. Contents of the pack and other information

1. What is Urokinasi Pfizer and what is it used for

Urokinasi Pfizer contains the active substance urokinase which is a protein and belongs to a group of
medicines called antithrombotic agents used for problems with blood coagulation.
Urokinasi Pfizer is indicated in conditions where blood circulation is obstructed (thrombosis) and therefore in
all forms of occlusion of veins and arteries caused by a recent
blood clot (thrombus) and in any case before there is irreversible damage.

2. What you need to know before using Urokinase Pfizer

Do not use Urokinase Pfizer

• if you are allergic to urokinase or any of the other ingredients of this medicine (listed in section 6);
• if you suffer from a blood problem characterised by poor blood clotting (congenital or acquired hypocoagulability);
• if you have suffered in the last 2 months from bleeding affecting the brain (thrombosis, embolisms, cerebral haemorrhages), have undergone surgery (cerebral and spinal) or if you have suffered in the last three months from stroke of any kind;
• if a significant blood loss is currently occurring or if you have a predisposition to blood loss;
• if you have brain tumors;
• if you have suffered a trauma in the last 10 days
• if you have undergone major surgery in the last two months;
• if you suffer from very high blood pressure;
• if you have inflammation of the heart (bacterial endocarditis, pericarditis);
• if you suffer from inflammation of the pancreas (acute pancreatitis);
• if you have liver problems such as severe hepatopathy, hepatic cirrhosis, portal hypertension and active hepatitis; if you are affected by oesophageal varices, stomach or intestinal ulcer or other ulcers of the gastrointestinal tract, documented in the last 3 months;
• if you suffer from problems with the veins and arteries such as arterial aneurysm, arteriovenous malformations; if you have kidney problems (severe renal insufficiency);
• if you suffer from chronic lung diseases associated with a risk of bleeding (bronchiectasis, bullous emphysema);
• if you suffer from fluid accumulation in the lungs (pulmonary edema);

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• if you are pregnant, if you are due to give birth shortly, if you have recently given birth, if you have recently had an abortion, if you have placenta previa and if you are breastfeeding (See section “Pregnancy and breastfeeding”);
• if a prosthesis has recently been applied to your veins;
• if you have undergone injections into a non-compressible blood vessel in the last 10 days, such as the subclavian or jugular vein. The doctor will assess the risks if you are to undergo organ biopsy, or if you have a high risk of thrombus formation in the left heart (e.g. mitral stenosis with atrial fibrillation, cerebrovascular diseases).

Warnings and precautions
Talk to your doctor or nurse before you are given Urokinase Pfizer.
This medicine will be administered to you in specialised centres by experienced medical personnel, who will
subject you to visits and specialist examinations before and during treatment, in particular to
monitor blood coagulation.
During treatment, medical personnel will need to subject you to blood tests (e.g. fibrinogen dosage, every 6-12 hours) especially if you are being treated with high doses of urokinase.
This medicine will not be administered to you if you suffer from health problems associated with an increased
risk of bleeding.
This medicine must be administered to you with great caution in the following cases:

• if you have suffered from bleeding in the brain (cerebrovascular diseases, cerebrovascular diseases associated with high blood pressure);
• if you are elderly;
• if you are menstruating;
• if you have a heart problem called atrial fibrillation;
• if you have recently undergone non-vascular invasive procedures, such as organ biopsy, lumbar puncture (a spinal tap). Invasive procedures such as injections into the arteries should be avoided before and during treatment with this medicine to minimise the risk of bleeding. Any intramuscular injection must also be avoided during treatment with urokinase. Bleeding may occur during perfusion, especially if therapy is prolonged for more than 48 hours. Although most bleeding associated with the use of urokinase occurs at the site of arterial puncture, bleeding may occur at any site. If you experience blood loss, the specialised medical personnel must stop administration and take appropriate safety measures.

Isolated cases of embolism due to fragments of the original clot have been reported.
The concomitant administration of urokinase with other medicines that act on blood coagulation,
such as thrombolytics, anticoagulants or antiplatelet agents, may increase the risk of bleeding
(see section “Other medicines and Urokinase Pfizer”).
UROKINASE PFIZER contains highly purified urokinase obtained from human urine. Medicines
produced with raw materials of human origin have the potential to transmit infectious agents. Inactivation and purification procedures reduce the risks almost completely, but the possibility of transmission of infectious agents cannot be totally excluded.
This also applies to viruses and other emerging or unknown pathogens.
In order to improve the traceability of the medicine, the name and batch number of the medicine
administered must be clearly recorded.
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Paediatric population
The safety and efficacy of urokinase in children have not been established.

Other medicines and Urokinase Pfizer
Tell your doctor if you are taking, have recently taken or might take any other medicines.
During treatment with Urokinase Pfizer you should avoid taking the following medicines:

• medicines for inflammation such as acetylsalicylic acid and other non-steroidal anti-inflammatory drugs;
• medicines that prevent coagulation (oral anticoagulants, heparin);
• medicines that affect platelet function (antiplatelet agents, dipyridamole, dextrans, serotonin reuptake inhibitors or SSRIs and serotonin and noradrenaline or SNRIs, abciximab, allopurinol, clofibric acid derivatives, clopidogrel, cytostatic agents, dextrans, dipyridamole, ticlopidine, tetracycline, valproic acid, thiouracils, sulphonamides);
• medicines that inhibit the fibrinolytic action of urokinase such as p-aminobenzoic acid, epsilon aminocaproic acid and tranexamic acid (antifibrinolytics).

Fertility, pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are breastfeeding,
ask your doctor for advice before using this medicine.
Urokinase Pfizer is contraindicated if you are pregnant, if you are due to give birth shortly, if you have recently given birth, if you have
had an abortion or if you are breastfeeding (See section “Do not use Urokinase Pfizer”).
It is not known whether UROKINASE PFIZER is excreted in human milk. The risk to newborns/infants cannot
be excluded. Therefore, UROKINASE PFIZER should not be used during breastfeeding.
There are no data available regarding the influence of treatment with urokinase on fertility.

Driving and using machines
Urokinase Pfizer does not impair or negligibly impairs the ability to drive vehicles and operate machinery.

Urokinase Pfizercontains sodium
This medicine contains less than 1 millimole (23 mg) of sodium per vial and bottle, i.e. essentially
sodium-free.

3. How to use Urokinasi Pfizer

This medicine will be administered to you by qualified medical personnel. If you have any doubts, consult your doctor or
nurse.
The doctor will determine the dose, the method of administration and the duration of treatment depending on your
health conditions, your illness and your weight.

If you use more Urokinasi Pfizerthan you should
This medicine will be administered to you by qualified medical personnel, so it is unlikely that you will be
administered an excessive dose. In case of overdose, bleeding may occur: generally, stopping the administration is
sufficient; but if the bleeding persists, the doctor will have to
subject you to therapy.
If you fear that you have been administered an excessive dose, inform your doctor or nurse.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

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Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects that may occur are listed below:

• allergic reactions, severe allergic reactions such as anaphylaxis;
• bleeding in the brain, stroke;
• heart problems (atrial reperfusion or ventricular arrhythmia);
• bleeding, low blood pressure (hypotension), onset of coagulation problems such as emboli (thromboembolism, pulmonary embolism);
• nosebleeds (epistaxis), difficulty breathing (dyspnea), bluish discoloration of the skin and mucous membranes (cyanosis);
• gum bleeding (gingival hemorrhage), bleeding in the gastrointestinal and retroperitoneal areas (gastrointestinal and retroperitoneal hemorrhage), intestinal lesions (intestinal perforation);
• skin rash, appearance of blood spots under the skin (purpura), urticaria, itching;
• bleeding from the liver (hepatic hemorrhage);
• presence of blood in the urine (hematuria), bleeding in the urogenital area, acute renal failure;
• appearance of a bruise (hematoma) at the infusion site and at the puncture site, reactions at the infusion site, fever, chills;
• decreased values of blood cells (decreased hematocrit), decreased hemoglobin values, increased liver enzyme values;
• collection of blood that forms between the two outer layers of the wall of an artery (vascular pseudoaneurysm).
• fever and chills (from breakdown of fibrin clots) Reporting of side effectsIf you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. You can also report side effects directly through the national reporting system at www.agenziafarmaco.gov.it/content/segnalazioni-reazioni- avverse. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Urokinasi Pfizer

Medical personnel are familiar with the storage conditions for Urokinasi Pfizer.
Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack after “Scad”.
The expiry date refers to the last day of that month.
Store this medicine at a temperature below 25°C.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Urokinase Pfizer contains

• The active substance is urokinase. The vial of powder for injectable solution 100,000 U.I./2 ml contains 100,000 U.I. of human urokinase.
• Other components are: o Vial of powder for injectable solution: mannitol, disodium edetate, disodium phosphate dodecahydrate; o solvent vial: sodium chloride, water for injections. See section 2 “Urokinase Pfizer contains sodium”. Page 4of 6

Description of the appearance of Urokinase Pfizerand contents of the pack
Each pack contains one vial of lyophilized powder and one vial of solvent.

Marketing Authorisation Holder
Pfizer Italia Srl – Via Isonzo, 71 – 04100 Latina

Manufacturer
Sirton Pharmaceuticals S.p.A. - Piazza XX Settembre, 2 - 22079 Villa Guardia (Co) – Italy.

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The following information is intended exclusively for healthcare professionals
Dosage and administration
Despite the multiplicity of therapeutic regimens used by different Authors, recent reviews indicate the following
dosages for the general treatment of thrombotic or embolic vascular occlusions. In pulmonary embolism: attack dose of 3,300 to 4,400 U.I./Kg of body weight in 10-15 minutes by rapid intravenous infusion
followed by a maintenance dose of 3,300-4,400 U.I./Kg/hour for 12 hours by slow infusion of the preparation
diluted in adequate volumes of saline or glucose solutions.
Good therapeutic results have also been obtained by administering an initial dose of 200,000-250,000
U.I./adult subject in 15 minutes by rapid intravenous infusion, followed by slow continuous infusion for 8-
12 hours up to a total of 1,500,000 U.I.
In myocardial infarction: 15,000-30,000 U.I./Kg administered by intravenous infusion lasting no
more than 90 minutes.
It is crucial for therapeutic success to start the administration of Urokinase as early as
possible.
In deep vein thrombosis, the following therapeutic regimen has been successfully used: a dose of 75,000
U.I./hour/subject for 12-24 hours, preceded or not by an attack dose of 150,000 U.I./subject.
It is useful to associate, or follow, thrombolytic treatment with urokinase with heparin treatment.
The association with heparin therapy, however, requires observance of the contraindications specific to this
anticoagulant and requires appropriate monitoring of the coagulation status (activated partial thromboplastin time) in order to avoid the occurrence of hyper- or hypocoagulable states.
Ophthalmological use: thrombosis of the central retinal vessels: administration and dosage as indicated for
general treatment.
Vitreous and anterior chamber hemorrhages of the eye: from 5,000 to 25,000 U.I. directly "in situ", in
single dose in small volume.
Various fibrin deposits: 5,000-10,000 U.I. directly "in situ" by intrasierous, intrathecal or
intraventricular administration in single dose, possibly repeatable according to clinical evolution.
Unblocking of artero-venous shunts: 5,000-25,000 U.I. introduced into the obstructed shunt and left "in situ"
for 1-2 hours.
Release by mechanical aspiration and possible repetition of the procedure.

Paediatric population
There is limited experience with urokinase in the paediatric population. The safety and efficacy
of UROKINASE PFIZER in children and adolescents under the age of 18 years have not been established.

Overdosage
In case of overdosage, appropriate supportive treatment should be initiated based on
the conditions of the patient, taking into account that overdosage can cause severe
bleeding events: generally, it is sufficient to stop the infusion of Urokinase Pfizer. If necessary, in cases
of persistent bleeding, it is advisable to administer natural antifibrinolytics such as aprotinin, or synthetic
ones such as epsilon aminocaproic acid (EACA). In case of severe deficiency of coagulation factors, it is
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appropriate to administer human fibrinogen or protein fraction I or whole plasma.
Avoid the administration of dextrans for the correction of blood volume depletion.

Incompatibilities
Urokinase Pfizer must only be reconstituted with the supplied vial of solvent.

Special precautions for storage
The medicine must be stored at a temperature below 25°C.
From a microbiological point of view, the product must be used immediately after reconstitution. If
not used immediately, the conditions and period of conservation before use are the responsibility
of the user. The chemical and physical stability of the medicine after reconstitution has been demonstrated for 48 hours
between +2°C and +8°C.
Please consult the Summary of Product Characteristics for more details
prescribing information.
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