UROCHINASI 25.000 U.I./2 ML Powder and solvent for injectable solution

Зміст інструкції

1. What is UROCHINASI EG and what is it used for
2. What you need to know before using UROCHINASI EG
3. How to use UROCHINASI EG
4. Possible side effects
5. How to store UROCHINASI EG
6. Package Contents and Other Information

“UROCHINASI EG 25,000 I.U./2 ml powder and solvent for injectable solution” 1 vial powder
+ 1 vial solvent 2ml
“UROCHINASI EG 100,000 I.U./2 ml powder and solvent for injectable solution” 1 vial powder
+ 1 vial solvent 2 ml
“UROCHINASI EG 250,000 I.U./5 ml powder and solvent for injectable solution” 1 vial powder
+ 1 vial solvent 5 ml
“UROCHINASI EG 500,000 I.U./5 ml powder and solvent for injectable solution” 1 vial powder
+ 1 vial solvent 5 ml
“UROCHINASI EG 1,000,000 I.U./5 ml powder and solvent for injectable solution” 1 vial
powder + 1 vial solvent 5 ml
Human urokinase

Read this leaflet carefully before you use 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 you get any side effects, see section 4, talk to your doctor or nurse.

Contents of this leaflet:

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

1. What is UROCHINASI EG and what is it used for

UROCHINASI EG contains the active ingredient human urokinase which is a protein extracted from human urine
and belongs to a group of medicines called antithrombotic agents used for problems in
blood coagulation.
UROCHINASI EG is indicated in conditions where blood circulation is obstructed (thrombosis and embolisms)
and therefore in all forms of occlusion of veins and arteries caused by a blood clot (thrombus) or
by air or gas (embolus) of recent formation such as: pulmonary embolism; occlusions of the peripheral arteries;
myocardial infarction (heart) caused by probable or confirmed thrombosis of the heart's coronary arteries; thrombosis
of the veins; cerebral thromboembolism (of the brain); thrombosis of the central vessels of the retina of the eye; bleeding
that affects the eye (vitreous and anterior chamber hemorrhages); blood clots due to
the presence of connections created surgically between veins and arteries (arteriovenous shunts).

2. What you need to know before using UROCHINASI EG

Do not use UROCHINASI EG

• 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 characterized by defects in blood coagulation;
• if you are currently experiencing or have recently experienced significant blood loss;
• if you have suffered bleeding in the brain in the last 2 months (cerebral haemorrhages);
• if you have had a stroke in the last 3 months;
• if you have undergone brain or spinal surgery in the last 2 months;
• if you have a brain tumour;
• if you have suffered a trauma in the last 10 days or have a wound caused by surgery that is not completely healed;
• if you have undergone major surgery in the last 2 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 liver failure, liver cirrhosis, portal hypertension and active hepatitis;
• if you have suffered from a stomach or intestinal ulcer or other ulcerative diseases of the gastrointestinal tract in the last 3 months or if you have oesophageal varices
• if you suffer from problems with veins and arteries such as arterial aneurysm, arteriovenous malformations;
• if you have recent vascular prostheses;
• if you have undergone injections into a non-compressible blood vessel such as the subclavian or jugular vein in the last 10 days;
• if you have kidney problems (severe renal failure);
• if you suffer from fluid accumulation in the lungs (pulmonary oedema) or chronic lung diseases associated with a risk of bleeding (bronchiectasis, bullous emphysema);
• if you are about to give birth or have just given birth;
• in case of abortion or if you have placenta previa (a condition in which the placenta is positioned above or near the cervix and can cause severe bleeding).
• if you are pregnant or breastfeeding (see Pregnancy and breastfeeding);

Warnings and precautions
Talk to your doctor or nurse before you are given UROCHINASI EG.
This treatment will only be carried out by experienced medical personnel in the administration of urokinase.
This medicine should be administered to you with great caution in the following cases:

• if you have suffered from problems with bleeding in the brain (haemorrhagic cerebral vasculopathies);
• if you are hypertensive (suffer from high blood pressure);
• if you experience an unexplained drop in blood pressure;
• if you are elderly, especially if you are over 75 years old;
• if you are menstruating;
• if you have a heart problem called atrial fibrillation;
• if you have recently undergone non-vascular invasive procedures (organ biopsy, spinal tap)

UROCHINASI EG may cause:

• bleeding (haemorrhage) at the site of administration and in other areas, especially for treatments lasting more than 48 hours;
• coagulation problems such as emboli, haemorrhagic purpura;

If you experience bleeding, the specialized medical personnel must stop the administration.
If severe bleeding occurs during treatment, UROCHINASI EG will be stopped and you
will be given medicines to control the bleeding.
Before starting and during treatment, medical personnel must subject you to blood tests to
check your coagulation status.
During treatment with UROCHINASI EG, arterial and intramuscular punctures will be avoided, due to
the risk of bleeding.
UROCHINASI EG 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
almost completely reduce the risks, but the possibility of transmission of infectious agents cannot be totally excluded.
This also applies to viruses and other emerging or unknown pathogens.

Other medicines and UROCHINASI EG
Tell your doctor or nurse if you are taking, have recently taken or might take any other
medicines, especially any of the following medicines that may increase the risk of bleeding:

• heparin or other oral anticoagulants (used to thin the blood);
• acetylsalicylic acid (aspirin) and other non-steroidal anti-inflammatory drugs (NSAIDs, used to treat pain and inflammation);
• some medicines used to treat depression and anxiety (
• antiplatelet agents (which prevent platelets from forming clots, such as abciximab, clopidogrel, dipyridamole, ticlopidine);
• cytostatic agents (medicines used to fight tumours);
• allopurinol (medicine to treat gout and other uric acid/urate deposition conditions);
• clofibric acid derivatives (used to lower blood fat levels);
• dextrans (substances used to increase blood volume);
• tetracycline and sulfonamides (antibiotics that act on bacteria that cause infections);
• valproic acid (for treating epilepsy);
• thiouracil (for thyroid problems);
• antifibrinolytics (used in the treatment of some haemorrhages, such as p-aminobenzoic acid, epsilon-aminocaproic acid, tranexamic acid).

Children and adolescents
The safety and efficacy of UROCHINASI EG in children and adolescents under the age of 18 have not been
established.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding,
ask your doctor or pharmacist for advice before using this medicine.
UROCHINASI EG is contraindicated if you are pregnant, are about to give birth, have recently given birth or
are breastfeeding.

Driving and using machines
UROCHINASI EG does not alter or negligibly alters the ability to drive vehicles and use
machinery.

UROCHINASI EG contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 5 ml of solution, i.e. essentially
‘sodium-free’.

3. How to use UROCHINASI EG

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, method of administration, and duration of treatment depending on your
health conditions, your illness, and your weight.

If you use more UROCHINASI EG than you should
This medicine will be administered to you by qualified medical personnel, making it unlikely that you
will be given an excessive dose. In case of overdose, bleeding may occur and
you will need to stop the administration. If the bleeding persists, your doctor will need to subject you to appropriate
therapy.
If you are concerned that you have been given an excessive dose, inform your doctor or nurse.
If you have any doubts about the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Bleeding is the most serious and most frequent side effect of urokinase-based therapy.
Severe bleeding events have been observed spontaneously, including fatal cases of cerebral haemorrhage.
During therapy, especially during infusions lasting more than 48 hours, bleeding may occur, especially at the site of perfusion.

Side effects with unknown frequency(frequency cannot be estimated based on available data):

• allergic reactions (hypersensitivity), severe allergic reaction with rapid onset that can be life-threatening (anaphylaxis);
• bleeding in the brain (intracranial haemorrhage), illness caused by insufficient blood flow to an area of the brain (stroke);
• bleeding, low blood pressure, formation of blood clots in a vein or artery (thromboembolism) or in the lungs (pulmonary embolism);
• nosebleeds (epistaxis), difficulty breathing (dyspnoea), skin turning blue (cyanosis);
• gum bleeding, gastrointestinal bleeding, retroperitoneal bleeding, intestinal perforation;
• skin rash, reddish spots on the skin (purpura), itching and small spots on the skin (urticaria), pruritus;
• liver bleeding;
• presence of blood in the urine (haematuria), urogenital bleeding, acute renal failure;
• blood loss under the skin (haematoma) at the infusion or puncture site, reactions at the infusion site, fever, chills;
• alteration of some values in the blood (decreased haematocrit, decreased haemoglobin, increased liver enzymes);
• vascular pseudoaneurysm.

Reporting of side effects
If 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 https://www.aifa.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 UROCHINASI EG

Medical personnel are familiar with the storage methods for UROCHINASI EG.
Keep this medicine out of the 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. Package Contents and Other Information

What UROCHINASI EG contains

• The active ingredient is urokinase. The 25,000 U.I./2 ml vial contains 25,000 U.I. of human urokinase; the 100,000 U.I./2 ml vial contains 100,000 U.I. of human urokinase; the vial of

• 250,000 U.I./5 ml contains 250,000 U.I. of human urokinase; the 500,000 U.I./5 ml vial contains 500,000 U.I. of human urokinase; the 1,000,000 U.I./5 ml vial contains 1,000,000 U.I. of human urokinase.
• The other ingredients are:
• powder vial: mannitol, disodium edetate, sodium phosphate;
• solvent vial: sodium chloride, water for injections.

Description of the appearance of UROCHINASI EG and contents of the pack
Each pack contains one powder vial and one solvent vial.
UROCHINASI EG 25,000 U.I.: 1 powder vial + 1 solvent vial of 2 ml
UROCHINASI EG 100,000 U.I.: 1 powder vial + 1 solvent vial of 2 ml
UROCHINASI EG 250,000 U.I.: 1 powder vial + 1 solvent vial of 5 ml
UROCHINASI EG 500,000 U.I.: 1 powder vial + 1 solvent vial of 5 ml
UROCHINASI EG 1,000,000 U.I.: 1 powder vial + 1 solvent vial of 5 ml.

Marketing Authorisation Holder
EG S.p.A. – Via Pavia, 6 – Milan - Italy

Manufacturers
SIRTON PHARMACEUTICALS S.p.A. - Villa Guardia (Como)
ALFA WASSERMANN S.p.A. Contrada S. Emidio - 65020 Alanno (Pescara)

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The following information is intended for healthcare professionals only
Dosage and Administration
UROCHINASI EG, following the therapeutic regimens indicated in the clinical literature, can be
administered as follows:

Pulmonary Embolism
Systemic treatment: as an initial dose 4,400 U.I./Kg (average 300,000 U.I.) for slow intravenous infusion (15-20 minutes) followed by 4,400 U.I./kg/hour for 12 hours with continuous infusion, dissolving
the lyophilized powder in 100-500 ml of physiological or glucose solution.
Administration by local infusion: administer through the catheter used for angiography, over a period of 5 minutes-2 hours, 300,000-1,000,000 U.I. dissolved in 50 ml of physiological solution.

Deep Vein Thrombosis

• 75,000 - 100,000 U.I. per hour for 12-72 hours. A loading dose of 150,000 - 200,000 U.I. by slow intravenous injection (15-30 minutes) may precede this.

Myocardial Infarction
Systemic treatment: 7,500 U.I./Kg in a single dose for slow intravenous infusion (10-15 minutes)
followed by 3,750 U.I./Kg/hour for 18 consecutive hours for continuous infusion.
Administration by local infusion: administer through the coronary catheter 300,000 U.I.,
dissolved in 375 ml of physiological solution in 75 minutes (flow rate of 5 ml per minute equal to 4,000 U.I. per
minute).

Central Retinal Vein Thrombosis

• 4,400 U.I./Kg in a single dose for intravenous infusion (10-15 minutes), followed by 4,400 U.I./Kg/hour for 4 hours for continuous intravenous infusion.

Vitreous Hemorrhage and Anterior Chamber Hemorrhage of the Eye

• 5,000 - 25,000 U.I. are applied directly in a single dose dissolved in small volumes.

Peripheral Arterial Thromboembolism
Systemic treatment: the same system as suggested for pulmonary embolism applies.
Administration by local infusion: 100,000 U.I. in 20 minutes, followed by 75,000 U.I./hour for 8-24 hours
administered by arterial catheterization.

Association with heparin:many authors consider the simultaneous administration of heparin useful during urokinase treatment. Doses and dosage regimens should be established on a case-by-case basis by
the treating physician.
Checks to be performed during therapy with UROCHINASI EG
During treatment with UROCHINASI EG, especially when adopting high dosage regimens, it is
advisable to monitor the fibrinolytic system by performing the following hematological tests: thrombin time, euglobulin lysis time, fibrinogen level and plasma fibrinogen level.

Overdose
Overdose can cause bleeding events: in such cases, it is sufficient to stop the infusion of
UROCHINASI EG. 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 the
event of severe alterations in coagulation factors, it is appropriate to administer human fibrinogen or
plasma protein fraction or whole plasma.

Incompatibilities
UROCHINASI EG must be reconstituted only with the attached solvent vial or in any case with
physiological solution or 5% glucose without preservatives.

Special precautions for storage
The medicine must be stored at a temperature not exceeding 25°C.
The reconstituted solution of UROCHINASI EG must be used immediately. If not used
immediately, the conditions and period of conservation before use are the responsibility
of the user. The reconstituted solution can be stored in the refrigerator between +2° and +8°C for 24 hours
(25,000 U.I.) and for 48 hours (all other dosages).