Leaflet: information for the user

Urokinase Teofarma 250,000 U.I. powder and solvent for solution for infusion

Urokinase

Read this leaflet carefully before you start using this medicine, because it contains important information for you.

Keep this leaflet, as you may need to read it again.
If you have any questions, consult your doctor or pharmacist.

This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.

If you experience any side effects, consult your doctor, even if they are not listed in this leaflet. See section 4.

1. What isUrokinase Teofarma 250,000 U.I.and what it is used for

2. What you need to know before you start usingUrokinase Teofarma 250,000 U.I.

3. How to use Urokinase Teofarma 250,000 U.I.

4. Possible side effects

5. Storage of Urokinase Teofarma 250,000 U.I.

6. Contents of the pack and additional information

Urokinase Teofarma belongs to a group of medications called antithrombotics.

Urokinase is a human urine-derived enzyme used to break down blood clots

(dissolve clots) and prevent the obstruction of blood vessels.

Urokinase Teofarma is indicated for:

• Treatment of thromboembolic conditions: peripheral arterial thromboembolism and deep vein thrombosis.
• Pulmonary embolism acute massive or pulmonary embolism with hemodynamic instability.
• Arterio-venous shunt thrombosis.
• Intravitreal hemorrhages.
• Coronary thrombosis: Urokinase has been used to destroy the acute thrombus obstructing coronary arteries associated with transmural myocardial infarction. Most patients receiving urokinase via intracoronary infusion within 6 hours of symptom onset show vasal reperfusion.

It has not been demonstrated that intracoronary administration of urokinase during transmural myocardial infarction achieves recovery of affected myocardial tissue, nor reduces mortality. The characteristics of patients who may benefit from this therapy have not been defined.

• Metastatic pleural effusions and complicated empyemas.

The treatment with urokinase must be performed always in a specialized institution and under strict medical supervision.

Do not use Urokinase Teofarma if you are in any of the following situations:

• Significant bleeding at the present time or during the last 6 months.
• Treatment with oral anticoagulants and an INR > 1.3 (laboratory parameter).
• History of central nervous system injury (e.g., neoplasm or tumor process, aneurysm or vascular dilation, intracranial or spinal surgery).
• Known predisposition to present bleeding.
• Uncontrolled severe hypertension.
• Important surgical procedures, biopsy, or organ sampling, or significant trauma during the last 2 months (including any trauma associated with the current acute myocardial infarction).
• Recent head or skull trauma.
• Prolonged cardiopulmonary resuscitation (> 2 minutes) during the last 2 weeks.
• Acute pericarditis or inflammation of the pericardium, and/or acute bacterial endocarditis or inflammation of the cardiac endocardium.
• Acute pancreatitis or inflammation of the pancreas.
• Severe liver alterations, including insufficiency or hepatic failure, cirrhosis, portal hypertension (esophageal varices), and active hepatitis.
• Active peptic ulcer.
• Aneurysm or arterial dilation and known arterial/venous malformation.
• Tumor process with increased risk of bleeding.
• Known history of stroke or cerebral vascular accident, transient ischemic attack, or dementia.
• If you are allergic (hypersensitive) to the active principle or to any of the other components of Urokinase Teofarma.

Be especially careful with Urokinase Teofarma

If you are in the following situations:

• Maximum systolic blood pressure value above 160 mmHg.
• Cerebral vascular disease.
• Recent gastrointestinal or genitourinary bleeding (within the last 10 days).
• High probability of presence of thrombi in the left heart cavities, e.g., mitral valve stenosis or occlusion of the heart with cardiac rhythm alteration or atrial fibrillation.
• Recent known intramuscular injection (within the last 2 days)
• Advanced age, e.g., over 75 years.
• If you are being treated with Urokinase Teofarma for pulmonary embolism, your doctor should perform a series of tests at least every 4 hours.

Injectable and intraarterial injections should be avoided during treatment.

Use of other medications

If administered with antiplatelet drugs (acetylsalicylic acid, indomethacin, phenylbutazone, etc.), oral anticoagulants, or heparin, the coagulation parameters should be frequently monitored, as the risk of bleeding increases.

Inform your doctor or pharmacist if you are using or have recently used other medications, including those purchased without a prescription.

Pregnancy and lactation

The safety of use during pregnancy and lactation has not been established, so it should be used with caution.

If you are pregnant or think you may be, inform your doctor before starting treatment.

If you are breastfeeding or plan to breastfeed, inform your doctor.

The excretion of Urokinase Teofarma in breast milk is unknown.The breast milk should be discarded during the first 24 hours after treatment.

Driving and operating machinery

Urokinase Teofarma does not interfere with the ability to drive and operate machinery.

Important information about some of the components of Urokinase Teofarma

This medication contains less than 23 mg (1 mmol) of sodium per dose, making it essentially "sodium-free".

Follow exactly the administration instructions of Urokinase Teofarma indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

The usual form of administration is by continuous intravenous infusion, dissolved in isotonic saline solution.

Urokinase should not be administered in the same mixture with other medications.

Acute massive pulmonary embolism or pulmonary embolism with instability

The recommended dosage for pulmonary embolism is: 4,400 U.I./kg in 10 minutes, as initial dose, followed by continuous infusion of 4,400 U.I./kg/hour for 12 hours.

Anticoagulant therapy

In the treatment of pulmonary embolism, it is usually recommended to follow the therapy with continuous infusion of heparin to prevent recurrence of the thrombus. The treatment with heparin, in case it is initiated, should not begin until the thrombin time value is less than double the normal control value (approximately 3-4 hours after suspending the infusion of urokinase).

Arterio-venous shunt occlusions

Use 5,000 – 10,000 U.I. dissolved in 0.5-1 ml of isotonic saline solution.

Intraocular hemorrhages

From 5,000 to 25,000 U.I., in direct intraocular instillation.

Pleural effusions with methanemomonas and complicated empyemas

The usual dosage is 100,000 U.I. three times a day for a period of approximately 2 to 6 days.

Once the catheter is located, the aspiration of all possible pleural fluid is performed. Then, 100,000 U.I. of Urokinase Teofarma dissolved in 10 ml of physiological serum are instilled, closing the catheter valve for 2 hours. Then, a new aspiration of the pleural fluid and a new instillation of urokinase are performed, repeating this operation a total of three times a day, until complete resolution of the pleural effusion and/or when the effusion debit is scarce in the last 24 hours (<20)

Use in children

The safety and efficacy of Urokinase Teofarma use in children have not been established.

Geriatric patients

In patients over 75 years old, the potential risk of an acute cerebrovascular accident should be evaluated. It is recommended to carefully select patients and monitor them.

If you use more Urokinase Teofarma than you should:

You may experience bleeding that may resolve by interrupting treatment. If necessary, in cases where bleeding persists, it is recommended to administer substances that neutralize the effect of urokinase, such as aprotinin, aminoacaproic acid, or tranexamic acid. In other cases, the administration of human plasma, complete plasma, or whole blood may be required.

A characteristic of urokinase to be taken into account is that it remains in the body for a short time and is rapidly eliminated.

In case of overdose or accidental ingestion, consult the Toxicological Information Service. Phone 915 620 420.

Like all medications, Urokinase Teofarma may produce adverse effects, although not all people may experience them.

Bleeding may occur at the injection site and, in isolated cases, generalized bleeding may occur.

Treatment with urokinase may produce rare mild allergic reactions, bronchospasm (contraction of the bronchial muscle that causes respiratory difficulty), skin reaction, and fever.

If an allergic reaction occurs, the infusion should be interrupted.

Like other thrombolytic agents (antithrombotic agents), some possible cardiovascular effects have been described, such as hypotension (decreased blood pressure), cardiac rhythm and frequency alterations, recurrent cardiac ischemia, or pulmonary obstruction due to embolism.

If you consider any of the adverse effects you are experiencing to be severe or if you notice any adverse effect not mentioned in this prospectus, inform your doctor or pharmacist.

Keep out of sight and reach of children.

Urokinase Teofarma once reconstituted must be stored at a temperature not exceeding 25°C.

Validity period of reconstituted solutions:

At room temperature (not more than 25°C): 24 hours.

Stored in refrigerator (2°C – 6°C): 48 hours.

Do not use Urokinase Teofarma after the expiration date appearing on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of packaging and unused medicines. By doing so, you will help protect the environment.

Composition of Urokinase Teofarma

The active principle is urokinase. Each vial of lyophilized powder contains 250,000 U.I. of urokinase.

The other components are: mannitol, disodium edetate 2 mg, and disodium phosphate 2.4 mg.

Each ampule of solvent contains: sodium chloride and water for injection.

Once the vial is reconstituted with the 5 ml of solvent, each vial contains 50,000 U.I. of urokinase/ml.

Appearance of the product and contents of the packaging

A vial containing lyophilized powder with 250,000 U.I. of urokinase and an ampule of 5 ml with solvent.

Clinical packaging with 10 vials of lyophilized powder and 10 ampules of solvent.

Other presentations

Urokinase Teofarma 100,000 U.I.:Clinical packaging with 25 vials of lyophilized powder and 25 ampules of solvent.

Holder of the marketing authorization and responsible for manufacturing

Holder:

Teofarma S.r.l.

Via F.lli Cervi, 8

27010 Valle Salimbene (PV)

Italy

Fax 0039/0382/525845

e-mail: [email protected]

Responsible for Manufacturing:

Sirton Pharmaceuticals S.P.A., Villa Guardia (Como), Italy.

This leaflet has been reviewed inSeptember 2023