Urokinase Pfizer

Package leaflet: Information for the user

UROKINASE PFIZER 100,000 IU/2 ml powder and solvent for injectable solution

Generic medicine
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 questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or nurse. See section 4.

Contents of this leaflet:

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

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

Urokinase Pfizer contains the active substance urokinase, which is a protein and belongs to a group of
medicinal products called antithrombotic agents, used for problems related to blood coagulation.
Urokinase Pfizer is indicated in conditions where blood circulation is obstructed (thrombosis), and thus in
all forms of occlusion of veins and arteries caused by a recently formed blood clot (thrombus), provided that
irreversible damage has not yet occurred.

2. What you need to know before using Urokinase Pfizer

Do not use Urokinase Pfizer

• 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 poor blood clotting (congenital or acquired hypocoagulability);
• if you have had bleeding affecting the brain (thrombosis, embolism, cerebral haemorrhage) within the last 2 months, have undergone brain or spinal surgery, or have had a cerebrovascular accident of any kind within the last three months;
• if you currently have significant bleeding or are predisposed to bleeding;
• if you have brain tumours;
• if you have suffered trauma within the last 10 days;
• if you have undergone major surgery within the last two 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 hepatopathy, hepatic cirrhosis, portal hypertension, or active hepatitis;
• if you have oesophageal varices, gastric or intestinal ulcer, or other gastrointestinal ulcers documented within the last 3 months;
• if you have vascular problems such as arterial aneurysm, or arterial and venous malformations;
• if you have kidney problems (severe renal failure);
• if you suffer from chronic lung diseases associated with a risk of bleeding (bronchiectasis, bullous emphysema);
• if you have fluid accumulation in the lungs (pulmonary oedema);
• if you are pregnant, about to give birth, have recently given birth, have recently had a miscarriage, have placenta praevia, or are breastfeeding (see section “Pregnancy and breastfeeding”);
• if you have recently had a venous prosthesis implanted;
• if you have received injections into a non-compressible blood vessel (e.g. subclavian or jugular vein) within the last 10 days. Your doctor will evaluate the risks if you need to undergo organ biopsy or if you are at high risk of forming blood clots in the left heart (e.g. mitral stenosis with atrial fibrillation, cerebrovascular diseases).

Warnings and precautions
Speak with your doctor or nurse before Urokinase Pfizer is administered to you.
This medicine will be administered in specialized centres by experienced medical personnel, who will perform specialist examinations before and during treatment, particularly to monitor blood coagulation.
During treatment, you will undergo blood tests (e.g. fibrinogen levels, every 6–12 hours), especially if you are receiving high doses of urokinase.
This medicine will not be administered to you if you have medical conditions associated with an increased risk of bleeding.
This medicine must be administered with great caution in the following cases:

• if you have previously experienced bleeding problems in the brain (cerebral vasculopathies, cerebral vasculopathies associated with high blood pressure);
• if you are elderly;
• if you are menstruating;
• if you have a heart condition called atrial fibrillation;
• if you have recently undergone invasive non-vascular procedures, such as organ biopsy or lumbar puncture (spinal tap). Invasive procedures such as arterial injections should be avoided before and during treatment with this medicine to minimize the risk of bleeding. Intramuscular injections must also be avoided during treatment with urokinase. Bleeding may occur at the infusion site, especially if therapy is prolonged beyond 48 hours. Although most bleeding associated with urokinase occurs at the arterial puncture site, haemorrhage may occur at any site. If you experience bleeding, specialized medical personnel must stop administration and take appropriate safety measures.

Isolated cases of embolism due to fragments of the original clot have been reported.
Concomitant administration of urokinase with other medicines affecting 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 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 excluded. This applies also to viruses and other emerging or unknown pathogens.
To improve traceability of the medicine, the name and batch number of the administered medicine must be clearly recorded.
Paediatric population
The safety and efficacy of urokinase in children have not been established.
Other medicines and Urokinase Pfizer
Inform your doctor if you are currently using, have recently used, or might use any other medicines.
During treatment with Urokinase Pfizer, you should avoid taking the following medicines:

• anti-inflammatory medicines such as acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs);
• medicines that prevent blood clotting (oral anticoagulants, heparin);
• medicines that affect platelet function (antiplatelet agents, dipyridamole, dextran, serotonin reuptake inhibitors or SSRIs, serotonin-noradrenaline reuptake inhibitors or SNRIs, abciximab, allopurinol, clofibrate derivatives, clopidogrel, cytostatic agents, dextran, dipyridamole, ticlopidine, tetracycline, valproic acid, thiouracils, sulfonamides);
• 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, planning to become pregnant, or are breastfeeding, consult your doctor before using this medicine.
Urokinase Pfizer is contraindicated if you are pregnant, about to give birth, have recently given birth, have had a miscarriage, or 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 must not be used during breastfeeding.
There are no available data regarding the effect of urokinase treatment on fertility.
Driving and using machines
Urokinase Pfizer does not alter or alters negligibly the ability to drive and use machines.
Urokinase Pfizer contains 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 Urokinase Pfizer

This medicine will be administered to you by specialized 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 according to your health condition, your illness, and your body weight.
If you use more Urokinase Pfizer than you should
Since this medicine will be administered by specialized medical personnel, it is unlikely that you will receive an excessive dose. In case of overdose, bleeding may occur: usually it is sufficient to stop the administration; however, if bleeding persists, your doctor will need to provide appropriate treatment.
If you think you have been given too much of this medicine, 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 everyone will experience them.
The side effects that may occur are listed below:

• allergic reactions, severe allergic reactions such as anaphylaxis;
• bleeding in the brain, cerebrovascular accident;
• heart problems (atrial reperfusion or ventricular arrhythmia);
• bleeding, low blood pressure (hypotension), development of coagulation disorders such as emboli (thromboembolism, pulmonary embolism);
• nosebleeds (epistaxis), breathing difficulties (dyspnea), bluish discoloration of the skin and mucous membranes (cyanosis);
• bleeding from the gums (gingival hemorrhage), gastrointestinal and retroperitoneal bleeding (gastrointestinal and retroperitoneal hemorrhage), intestinal damage (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), urogenital bleeding, acute kidney failure;
• formation of a bruise (hematoma) at the infusion site and puncture site, infusion site reactions, fever, chills;
• decreased blood cell counts (decreased hematocrit), decreased hemoglobin levels, increased liver enzyme levels;
• collection of blood between the two outer layers of the arterial wall (vascular pseudoaneurysm);
• fever and chills (due to rupture of fibrin clots).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or nurse. You may also report side effects directly via 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 Urokinase Pfizer

Medical personnel are aware of the storage requirements for Urokinase Pfizer.
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 at a temperature below 25°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Urokinase Pfizer contains

• The active substance is urokinase. The 100,000 IU/2 ml vial of powder for injectable solution contains 100,000 IU of human urokinase.
• The other components are:
  o Vial of powder for injectable solution: mannitol, edetate disodium, disodium phosphate dodecahydrate;
  o Solvent vial: sodium chloride, water for injectable preparations. See section 2 “Urokinase Pfizer contains sodium”.

Description of the appearance of Urokinase Pfizer and package contents
Each package contains one vial of lyophilized powder and one vial of solvent.
Marketing Authorization Holder
Pfizer Italia Srl – Via Isonzo, 71 – 04100 Latina
Manufacturer
Sirton Pharmaceuticals S.p.A. - Piazza XX Settembre, 2 - 22079 Villa Guardia (Co) – Italy.

The following information is intended exclusively for healthcare professionals

Dosage and administration
Despite the variety of therapeutic regimens used by different authors, recent reviews indicate the following dosages for systemic treatment of vascular thrombotic or embolic occlusions.

In pulmonary embolism: an initial loading dose of 3,300 to 4,400 IU/kg body weight administered over 10–15 minutes by rapid intravenous infusion, followed by a maintenance dose of 3,300–4,400 IU/kg/hour for 12 hours by slow infusion of the diluted preparation in appropriate volumes of saline or glucose solutions.

Good therapeutic results have also been achieved by administering an initial dose of 200,000–250,000 IU per adult patient over 15 minutes by rapid intravenous infusion, followed by continuous slow infusion for 8–12 hours up to a total dose of 1,500,000 IU.

In myocardial infarction: 15,000–30,000 IU/kg administered by intravenous infusion over a period not exceeding 90 minutes.

For successful therapy, it is essential to initiate urokinase administration as early as possible.

In deep venous thrombosis, the following therapeutic regimen has been successfully used: a dose of 75,000 IU/hour per patient for 12–24 hours, preceded or not by a loading dose of 150,000 IU per patient.

Heparin therapy is useful either concomitantly with or following thrombolytic treatment with urokinase. However, combination with heparin requires adherence to the contraindications associated with this anticoagulant and appropriate monitoring of coagulation status (activated partial thromboplastin time) to avoid the occurrence of hyper- or hypocoagulability.

Ophthalmic use: central retinal vessel thrombosis: administration and dosage as indicated for systemic treatment.

Vitreous and anterior chamber hemorrhages: 5,000 to 25,000 IU administered directly "in loco" as a single dose in a small volume.

Various fibrinous deposits: 5,000–10,000 IU administered directly "in loco" by intraserosal, intrathecal, or intraventricular route as a single dose, repeatable if clinically indicated.

Clearing of obstructed arteriovenous shunts: 5,000–25,000 IU injected into the obstructed shunt and left in situ for 1–2 hours.

Followed by mechanical aspiration and, if necessary, repetition of the procedure.

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

Overdose
In case of overdose, appropriate supportive treatment should be initiated according to the patient's clinical condition. Overdose may cause severe hemorrhagic events; generally, discontinuation of Urokinase Pfizer infusion is sufficient. If necessary, in cases of persistent bleeding, administration of natural antifibrinolytics such as aprotinin or synthetic agents such as epsilon amino caproic acid (EACA) is recommended. In case of severe deficiency of coagulation factors, administration of human fibrinogen, plasma protein fraction I, or whole plasma is appropriate.

Avoid administration of dextrans for correction of blood volume depletion.

Incompatibilities
Urokinase Pfizer must be reconstituted only with the solvent provided in the accompanying vial.

Special precautions for storage
The medicinal product must be stored at a temperature not exceeding 25°C.

From a microbiological standpoint, the product should be used immediately after reconstitution. If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user. Chemical and physical stability of the medicinal product after reconstitution has been demonstrated for 48 hours between +2°C and +8°C.

Please refer to the Summary of Product Characteristics for further prescribing details.