UROKINASE TEOFARMA 100,000 IU POWDER AND SOLVENT FOR SOLUTION FOR INFUSION

2. Before using Urokinase Teofarma 100,000 U.I.

Treatment with urokinase should always be carried out in a specialized institution and under strict medical supervision.

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

• Major bleeding at present or during the last 6 months.
• Treatment with oral anticoagulants and INR > 1.3 (laboratory parameter).
• History of central nervous system injury (e.g., neoplasia or tumor process, aneurysm or vascular dilation, intracranial or spinal surgery).
• Known predisposition to bleeding.
• Uncontrolled severe hypertension.
• Major surgical procedures, biopsy, or sampling of organs 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.
• Pericarditis or acute pericardial inflammation and/or endocarditis or infectious cardiac endocarditis of bacterial origin.
• Pancreatitis or acute pancreatic inflammation.
• Severe liver disorders, including insufficiency or liver failure, cirrhosis, portal hypertension (esophageal varices), and active hepatitis.
• Active peptic ulcer.
• Aneurysm or arterial dilation and known arteriovenous malformation.
• Tumor process with increased risk of bleeding.
• Known history of stroke or cerebral vascular accident, transient cerebral ischemia, or dementia.
• If you are allergic (hypersensitive) to the active substance or to any of the other components of Urokinase Teofarma.

Be careful with Urokinase Teofarma

If you are in the following situations:

• Maximum blood pressure value above 160 mmHg.
• Cerebrovascular disease.
• Recent bleeding (during the last 10 days) of gastrointestinal or genitourinary origin.
• High probability of thrombi presence in the left heart cavities, e.g., in occlusion or stenosis of the mitral valve of the heart with altered cardiac rhythm or atrial fibrillation.
• Any recent intramuscular injection (during 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 four hours.

Intramuscular and intraarterial injections should be avoided during treatment.

Use of other medicines

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

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription.

Pregnancy and breastfeeding

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

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

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

It is not known whether Urokinase Teofarma is excreted in breast milk. Breast milk should be discarded during the first 24 hours after treatment.

Driving and using machines

Urokinase Teofarma does not interfere with the ability to drive and use machines.

Important information about some of the components of Urokinase Teofarma

This medicine contains less than 23 mg (1 mmol) of sodium per dose, so it is considered essentially "sodium-free".

3. How to use Urokinase Teofarma 100,000 U.I.

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

Massive or hemodynamically unstable acute pulmonary embolism

The recommended regimen for pulmonary embolism is: 4,400 U.I./kg in 10 minutes, as an 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 indicated to follow the therapy with continuous infusion of heparin to prevent thrombus recurrence. Treatment with heparin, if initiated, should not begin until the thrombin time value is less than twice the normal control value (approximately 3-4 hours after suspending urokinase infusion).

Arteriovenous 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.

Metapneumonic pleural effusions and complicated empyemas

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

Once the catheter is placed, all possible pleural fluid is aspirated. 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 pleural fluid and a new instillation of urokinase are performed, repeating this operation a total of three times a day, until the complete resolution of the pleural effusion and/or when the flow of the same is scarce in the last 24 hours (<20 ml) and or when the biological marker of fibrinolytic activity (d-dimer) demonstrates treatment ineffectiveness.< p>

Use in children

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

Elderly patients

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

If you use more Urokinase Teofarma than you should:

It may cause bleeding that can disappear when treatment is interrupted. If necessary, in cases where bleeding persists, it is advisable to administer substances that neutralize the effect of urokinase, such as aprotinin, aminocaproic acid, or tranexamic acid. In other cases, administration of human blood 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 Toxicology Information Service. Telephone 915 620 420.

4. Possible side effects

Like all medicines, Urokinase Teofarma can cause side effects, although not everybody gets them.

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

Treatment with urokinase may rarely cause mild allergic reactions, bronchospasm (contraction of bronchial muscle that causes difficulty breathing), skin reaction, and fever.

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

As with other thrombolytic agents (antithrombotics), some possible cardiovascular effects have been described, such as hypotension (decrease in blood pressure), alterations in cardiac rhythm and frequency, recurrent cardiac ischemia, or pulmonary embolism.

If you consider that any of the side effects you are suffering from is serious or if you notice any side effect not mentioned in this leaflet, inform your doctor or pharmacist.

5. Storage of Urokinase Teofarma 100,000 U.I.

Keep out of sight and reach of children.

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

Validity period of the reconstituted solutions:

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

Kept in the refrigerator (2°C - 6°C): 48 hours.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Contents of the pack and other information

Composition of Urokinase Teofarma

The active substance is urokinase. Each vial of lyophilized powder contains 100,000 U.I. of urokinase.

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

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

Once the vial is reconstituted with 2 ml of solvent, each vial contains 50,000 U.I. of urokinase/ml.

Appearance of the product and contents of the pack

A vial with lyophilized powder containing 100,000 U.I. of urokinase and an ampoule of 2 ml with solvent.

Clinical packaging with 25 vials of lyophilized powder and 25 ampoules of solvent.

Other presentations

Urokinase Teofarma 250,000 U.I.: Clinical packaging with 10 vials of lyophilized powder and 10 ampoules of solvent.

Marketing Authorization Holder and Manufacturer

Holder:

Teofarma S.r.l.

Via F.lli Cervi, 8

27010 Valle Salimbene (PV)

Italy

Fax 0039/0382/525845

e-mail: [email protected]

Manufacturer:

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

This leaflet was revised in

September 2023