Urokinase Eg

Package leaflet: Information for the user

“UROCHINASE EG 25,000 IU/2 ml powder and solvent for injectable solution” 1 vial of powder
+ 1 vial of solvent 2 ml
“UROCHINASE EG 100,000 IU/2 ml powder and solvent for injectable solution” 1 vial of powder
+ 1 vial of solvent 2 ml
“UROCHINASE EG 250,000 IU/5 ml powder and solvent for injectable solution” 1 vial of powder
+ 1 vial of solvent 5 ml
“UROCHINASE EG 500,000 IU/5 ml powder and solvent for injectable solution” 1 vial of powder
+ 1 vial of solvent 5 ml
“UROCHINASE EG 1,000,000 IU/5 ml powder and solvent for injectable solution” 1 vial of powder
+ 1 vial of solvent 5 ml
Human Urokinase
Please read all of this leaflet carefully before you use this medicine because it contains important
information for you.

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

Contents of this leaflet:

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

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

UROCHINASE EG contains the active substance human urokinase, a protein extracted from human urine,
and belongs to a group of medicines called antithrombotic agents, used for blood clotting disorders.
UROCHINASE EG is indicated in conditions where blood circulation is impaired (thrombosis and embolism),
and thus in all forms of occlusion of veins and arteries caused by a blood clot (thrombus) or by air or gas (embolus) of recent origin, such as: pulmonary embolism; occlusions of peripheral arteries; myocardial infarction (heart attack) caused by probable or confirmed thrombosis of the coronary arteries; venous thrombosis; cerebral thromboembolism (in the brain); thrombosis of the central retinal vessels of the eye; bleeding affecting the eye (vitreous and anterior chamber haemorrhages); blood clots associated with surgically created connections between arteries and veins (arteriovenous shunts).

2. What you need to know before using UROCHINASE EG

Do not use UROCHINASE EG

• if you are allergic to urokinase or to any of the other ingredients of this medicine (listed in section 6);
• if you have a blood disorder characterized by impaired blood clotting;
• if you are currently experiencing or have recently had significant bleeding;
• if you have had bleeding affecting the brain (cerebral haemorrhage) within the last 2 months;
• if you have had a stroke within the last 3 months;
• if you have undergone brain or spinal surgery within the last 2 months;
• if you have a brain tumour;
• if you have suffered trauma within the last 10 days or have a surgical wound that has not fully healed;
• if you have undergone major surgery within the last 2 months;
• if you have very high blood pressure;
• if you have inflammation of the heart (bacterial endocarditis, pericarditis);
• if you have inflammation of the pancreas (acute pancreatitis);
• if you have liver problems such as severe hepatic insufficiency, hepatic cirrhosis, portal hypertension, or active hepatitis;
• if you have suffered from stomach or intestinal ulcers or other ulcerative gastrointestinal diseases within the last 3 months, or if you have oesophageal varices;
• if you have problems with blood vessels such as arterial aneurysm, arteriovenous malformations;
• if you have recent vascular prostheses;
• if you have received injections into a non-compressible blood vessel (such as subclavian or jugular vein) within the last 10 days;
• if you have kidney problems (severe renal insufficiency);
• if you have pulmonary oedema (fluid accumulation in the lungs causing swelling) or chronic lung diseases associated with bleeding risk (bronchiectasis, bullous emphysema);
• if you are about to give birth or have recently given birth;
• in case of abortion or if you have placenta praevia (a condition in which the placenta covers or lies close to the cervix, which may cause severe bleeding);
• if you are pregnant or breastfeeding (see Pregnancy and breastfeeding);

Warnings and precautions
Talk to your doctor or nurse before UROCHINASE EG is administered to you.
This treatment will only be performed by medical personnel experienced in the administration of urokinase.
This medicine should be administered with caution in the following cases:

• if you have previously experienced bleeding problems in the brain (haemorrhagic cerebrovascular disease);
• if you are hypertensive (have high blood pressure);
• if you experience unexplained drop in blood pressure;
• if you are elderly, particularly if over 75 years of age;
• if you are menstruating;
• if you have a heart condition called atrial fibrillation;
• if you have recently undergone invasive non-vascular procedures (e.g. organ biopsy, lumbar puncture).

UROCHINASE EG may cause:

• bleeding (haemorrhage) at the administration site or elsewhere, especially with treatments lasting longer than 48 hours;
• coagulation disorders such as embolism, haemorrhagic purpura.

If you experience bleeding, specialized medical personnel must stop administration.
If severe bleeding occurs during treatment, UROCHINASE EG will be discontinued and you will be given medicines to control the bleeding.
Before starting and during treatment, medical personnel will perform blood tests to monitor your coagulation status.
During treatment with UROCHINASE EG, arterial and intramuscular injections will be avoided due to the risk of bleeding.
UROCHINASE EG contains highly purified urokinase derived from human urine. Medicines produced from human-source materials carry a potential risk of transmitting infectious agents. Inactivation and purification procedures reduce this risk almost completely, but the possibility of transmission of infectious agents cannot be entirely ruled out. This also applies to viruses and other emerging or unknown pathogens.

Other medicines and UROCHINASE EG
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines, especially 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);
• certain medicines used to treat depression and anxiety;
• antiplatelet drugs (which prevent platelets from forming clots, such as abciximab, clopidogrel, dipyridamole, ticlopidine);
• cytostatic agents (medicines used to fight tumours);
• allopurinol (a medicine used to treat gout and other conditions involving uric acid/urate deposition);
• clofibric acid derivatives (used to lower blood lipid levels);
• dextrans (substances used to increase blood volume);
• tetracycline and sulfonamides (antibiotics acting against bacteria causing infections);
• valproic acid (used to treat epilepsy);
• thiouracil (used for thyroid disorders);
• antifibrinolytic agents (used in the treatment of certain bleeding conditions, such as p-aminobenzoic acid, ε-aminocaproic acid, tranexamic acid).

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

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
UROCHINASE EG is contraindicated if you are pregnant, about to give birth, have recently given birth, or are breastfeeding.

Driving and using machines
UROCHINASE EG does not affect or has negligible effect on the ability to drive or operate machinery.

UROCHINASE 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 UROCHINASE EG

This medicine will be administered to you by specialized medical personnel. If you have any doubts, consult your doctor or nurse.
Your doctor will determine the dose, method of administration, and duration of treatment according to your health condition, your illness, and your body weight.
If you are given more UROCHINASE EG than you should
Since this medicine is administered by specialized medical personnel, it is unlikely that you will receive an excessive dose. In case of overdose, bleeding may occur and administration must be stopped. If bleeding persists, your doctor will need to initiate appropriate therapy.
If you think you have been given too much, inform your doctor or nurse immediately.
If you have any doubts about how to use this medicine, consult 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 common side effect of urokinase therapy.
Severe episodes of spontaneous bleeding have been observed, including fatal cases of cerebral haemorrhage.
During therapy, especially during infusions lasting more than 48 hours, bleeding may occur, particularly at the perfusion site.

Side effects with unknown frequency (cannot be estimated from the available data):

• allergic reactions (hypersensitivity), severe and rapidly occurring allergic reaction that may be fatal (anaphylaxis);
• bleeding in the brain (intracranial haemorrhage), illness caused by lack of blood flow to an area of the brain (cerebrovascular accident);
• haemorrhage, low blood pressure, formation of blood clots in a vein or artery (thromboembolism) or in the lungs (pulmonary embolism);
• nosebleeds (epistaxis), difficulty in breathing (dyspnoea), bluish discoloration of the skin (cyanosis);
• gum bleeding, gastrointestinal haemorrhage, retroperitoneal haemorrhage, intestinal perforation;
• skin rash, reddish spots on the skin (purpura), itching and small skin spots (urticaria), pruritus;
• bleeding in the liver;
• presence of blood in the urine (haematuria), urogenital haemorrhage, acute renal failure;
• bleeding under the skin (haematoma) at the infusion or puncture site, infusion site reactions, fever, chills;
• changes in certain blood values (decreased haematocrit, decreased haemoglobin, increased liver enzymes);
• pseudoaneurysm.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse.
You can also report side effects directly via 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 aware of the storage conditions for UROCHINASI EG.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after “Exp”.
The expiry date refers to the last day of that month.
Store this medicine below 25°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What UROCHINASI EG contains

• The active substance is urokinase. The 25,000 IU/2 ml vial contains 25,000 IU of human urokinase; the 100,000 IU/2 ml vial contains 100,000 IU of human urokinase; the 250,000 IU/5 ml vial contains 250,000 IU of human urokinase; the 500,000 IU/5 ml vial contains 500,000 IU of human urokinase; the 1,000,000 IU/5 ml vial contains 1,000,000 IU of human urokinase.

• The other components 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 IU: 1 powder vial + 1 solvent vial of 2 ml
UROCHINASI EG 100,000 IU: 1 powder vial + 1 solvent vial of 2 ml
UROCHINASI EG 250,000 IU: 1 powder vial + 1 solvent vial of 5 ml
UROCHINASI EG 500,000 IU: 1 powder vial + 1 solvent vial of 5 ml
UROCHINASI EG 1,000,000 IU: 1 powder vial + 1 solvent vial of 5 ml.

Marketing Authorization 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)

The following information is intended exclusively for healthcare professionals

Dosage and administration
UROCHINASE EG, according to the therapeutic regimens reported in clinical literature, may be administered as follows:

Pulmonary embolism
Systemic treatment: initial dose of 4,400 IU/kg (average 300,000 IU) administered by slow intravenous infusion (15–20 minutes), followed by 4,400 IU/kg/hour for 12 hours by continuous infusion, dissolving the lyophilisate in 100–500 mL of physiological saline or glucose solution.
Local infusion administration: 300,000–1,000,000 IU dissolved in 50 mL of physiological saline, administered through the catheter used for angiography over a period of 5 minutes to 2 hours.

Deep vein thrombosis
75,000–100,000 IU/hour for 12–72 hours.
This may be preceded by a loading dose of 150,000–200,000 IU given by slow intravenous injection (15–30 minutes).

Myocardial infarction
Systemic treatment: single dose of 7,500 IU/kg by slow intravenous infusion (10–15 minutes), followed by 3,750 IU/kg/hour for 18 consecutive hours by continuous infusion.
Local infusion administration: 300,000 IU administered through the intracoronary catheter, dissolved in 375 mL of physiological saline over 75 minutes (flow rate of 5 mL per minute, equivalent to 4,000 IU per minute).

Retinal central vessel thrombosis
Single dose of 4,400 IU/kg by intravenous infusion (10–15 minutes), followed by 4,400 IU/kg/hour for 4 hours by continuous intravenous infusion.

Vitreous and anterior chamber ocular haemorrhage
5,000–25,000 IU applied directly as a single dose, dissolved in small volumes.

Peripheral arterial thromboembolism
Systemic treatment: the same regimen recommended for pulmonary embolism applies.
Local infusion administration: 100,000 IU over 20 minutes, followed by 75,000 IU/hour for 8–24 hours administered by intra-arterial infusion.

Association with heparin:
Concomitant administration of heparin is considered beneficial by many authors during urokinase treatment. Doses and dosage regimens should be determined on a case-by-case basis by the attending physician.

Monitoring during UROCHINASE EG therapy
During treatment with UROCHINASE EG, especially when high-dose regimens are used, it is advisable to monitor the fibrinolytic system by performing the following haematological tests: thrombin time, euglobulin lysis time, blood fibrinogen level, and plasma fibrinogen level.

Overdose
Overdose may lead to haemorrhagic events: in such cases, it is sufficient to discontinue the infusion of UROCHINASE EG. If necessary, in cases of persistent bleeding, administration of natural antifibrinolytics such as aprotinin, or synthetic ones such as epsilon-aminocaproic acid (EACA) is recommended. In cases of severe coagulation factor disturbances, administration of human fibrinogen, plasma protein fraction, or whole plasma is appropriate.

Incompatibilities
UROCHINASE EG must be reconstituted only with the supplied solvent vial or, otherwise, with preservative-free physiological saline or 5% glucose solution.

Special precautions for storage
The medicinal product must be stored at a temperature not exceeding 25°C.
The reconstituted solution of UROCHINASE EG should be used immediately. If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user. The reconstituted solution may be stored in a refrigerator between +2°C and +8°C for 24 hours (25,000 IU) and for 48 hours (all other dosage strengths).