Leaflet: information for the user

Treosulfano Zentiva 5 g powder for solution for infusion EFG

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

1. What Treosulfano Zentiva is and what it is used for

2. What you need to know before you start using Treosulfano Zentiva

3. How to use Treosulfano Zentiva

4. Possible side effects

5. Storage of Treosulfano Zentiva

6. Contents of the pack and additional information

Treosulfano Zentiva contains the active ingredient treosulfano. Treosulfano belongs to the group of alkylating agents. These agents act by stopping the growth of cancer cells.

Treosulfano Zentiva has been prescribed for you by your doctorfor the treatment of advanced ovarian cancer after, at least, a previous standard treatment.

No use Treosulfano Zentiva:

• if you are allergic to treosulfano;
• if you do not have enough blood cells (severe suppression of the bone marrow);
• if you are breastfeeding.

Before each administration, a blood test should be performed to verify that you have enough blood cells to receive Treosulfano Zentiva.

Warnings and precautions

Consult your doctor or nurse before starting to use Treosulfano Zentiva if:

• you develop inflammation of the lungs that causes breathing difficulty (allergic alveolitis or pulmonary fibrosis). If this happens, treatment with Treosulfano Zentiva should be suspended.

You should be aware of the following aspects while undergoing treatment with Treosulfano Zentiva:

• your risk of developing certain types of infections increases;
• different types of blood cancer may occur after prolonged treatment;
• if you have kidney problems, treosulfano is excreted through the kidneys, therefore, strict control of your blood counts and, if necessary, adjustment of your dose should be performed;
• treatment with cancer medications may increase the risk of generalized infection after some vaccinations. Therefore, you should avoid being vaccinated with live vaccines;
• due to the possible development of inflammation in the bladder that causes pain or urinate more frequently or urgently, with or without blood in the urine (hemorrhagic cystitis), you are recommended to drink more liquids than normal for 24 hours after your treatment with treosulfano.
• If you are a fertile woman, you should also use effective contraceptive methods (i.e., pregnancy prevention) during and up to six months after treatment (see Pregnancy and breastfeeding section).

Other medications and Treosulfano Zentiva

Inform your doctor if you are using, have used recently or may need to use any other medication.

The effect of treatment with ibuprofen / chloroquine may be reduced when administered with Treosulfano Zentiva.

Pregnancy andlactation

If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor before using this medication. There are no data, or these are scarce, regarding the use of Treosulfano Zentiva 5 g powder for solution for infusion in pregnant women or breastfeeding women.

Pregnancy

Since fetal damage cannot be ruled out, Treosulfano Zentiva 5 g powder for solution for infusion should not be used during pregnancy, unless your doctor considers it absolutely necessary. You should not become pregnant during treatment with Treosulfano Zentiva 5 g powder for solution for infusion.

If you become pregnant during treatment with Treosulfano Zentiva 5 g powder for solution for infusion, you should inform your doctor immediately.

Contraception in women

During and up to six months after treatment with Treosulfano Zentiva 5 g powder for solution for infusion, you should use suitable contraceptive methods if you are fertile.

Lactation

Since it cannot be ruled out that the substance may be transferred to breast milk, you should not breastfeed during treatment with Treosulfano Zentiva 5 g powder for solution for infusion.

Driving and operating machines

Do not drive and do not operate machines if you have nausea and vomiting, as these effects may reduce your ability to drive or operate machinery.

Treosulfano Zentiva is usually administered by a doctor or nurse directly into the circulatory system. Your doctorwill calculate the correct dose for youand will be administered (intravenous infusion) over 15 to 30 minutes.

Your doctor will calculate the correct dose of Treosulfano Zentiva, based on your blood cell counts. Your doctor will reduce the dose if you have been given another anticancer medication or radiation therapy. The dose will also depend on your body size and will vary according to your body surface area.

During treatment with Treosulfano Zentiva, infusions are normally given every 3 to 4 weeks. In general, 6 treatment cycles are given.

Your doctor may change the dose and frequency of your treatment based on the results of your blood tests, your overall condition, any additional treatment you are receiving, and your response to Treosulfano Zentiva treatment. In case of doubt, ask your doctor or nurse.

If you experience pain at the injection site, inform your doctor or nurse immediately.

Use in children

It is not recommended for use in children

If you receive more Treosulfano Zentiva than you should

If you have been given too much of this medication, you may feel unwell or your blood cells may be reduced. Your doctor may give you a blood transfusion and take other measures if necessary

If you have any doubts about the use of this medication, ask your doctor, pharmacist, or nurse.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.If you experience any side effect, it is essential to inform your doctor before the next treatment.

Inform your doctor immediately if you notice any of the following symptoms:

• Allergic reactions[rare (may affect up to 1 in 1000 people)]: if you develop itching, skin rash, facial swelling, lip, tongue, and/or throat swelling, which may cause difficulty swallowing or breathing or a decrease in blood pressure.
• Fever or infection[very common (may affect more than 1 in 10 people)]: if you have a body temperature of 38°C or higher, experience sweating, or observe any other signs of infection (you may have fewer white blood cells than normal).
• Weakness[very common (may affect more than 1 in 10 people)], difficulty breathing, or if your skin becomes pale (you may have fewer red blood cells than normal).
• Bleeding[very common (may affect more than 1 in 10 people)]from the gums, mouth, or nose, or abnormal bruising (you may have fewer platelets than normal).
• Difficulty breathing[very rare (may affect up to 1 in 10,000 people)](you may have an allergic reaction, inflammation, or lung infection)

Very common side effects (may affect more than 1 in 10 people):

• Stomach problems, including nausea (feeling sick) with or without vomiting (being sick).
• Mild hair loss. After treatment, normal hair growth returns.
• Bronze-like skin discoloration.

Common side effects (may affect up to 1 in 10 people):

• Infections caused by fungi, viruses, or bacteria.

Uncommon side effects (may affect up to 1 in 100 people):

• Different types of blood cancers (after long-term treatments).

Very rare side effects (may affect up to 1 in 10,000 people):

• Severe general infection (sepsis).
• Addison's disease, a condition in which the adrenal glands do not function correctly, resulting in bronze-like skin, stomach discomfort, low blood pressure (dizziness), and a general feeling of weakness.
• Sweating, tremors, and hunger due to a decrease in blood glucose levels (hypoglycemia).
• Tickling and numbness (paresthesia).
• Cardiac muscle weakness caused by a structural change (cardiomyopathy).
• Hives or itchy rash; skin inflammation with or without scaly formation (scleroderma and psoriasis), skin redness (erythema).
• Bladder inflammation, causing pain or more frequent and urgent urination, with or without blood in the urine (hemorrhagic cystitis).
• General feeling of discomfort (symptoms similar to the flu).
• Painful redness or swelling at the injection site (in case the treosulfan solution leaks and comes into contact with the skin).

Inform your doctor or nurse immediately if you notice any of the above symptoms.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears onthepackageafter CAD. The expiration date is the last day of the month indicated.

Once reconstituted, do not store the medication in the refrigerator (2 - 8°C) as it may precipitate. Do not use if the solution contains precipitates.

Do not refrigerate.

The physical-chemical stability in use has been demonstrated for 12 hours at 30°C. From a microbiological standpoint, unless the dilution has been performed in controlled and validated aseptic conditions, it should be used immediately. If not, the storage times during use and the conditions prior to use are the responsibility of the user.

Medications should not be disposed of through drains or in the trash. Ask your pharmacisthow to disposeofthepackaging and of themedications that you no longerneed. In this way, you will help protect the environment.

Composition of Treosufano Zentiva

• The active ingredient is treosulfano. Each vial contains 5 g of treosulfano.
• After reconstitution, each milliliter of solution contains 50 mg of treosulfano

Appearance of the product and contents of the package

White crystalline powder or compact aggregate that is supplied in transparent glass vials, each vial contains 5 g of treosulfano.

The powder is reconstituted with water for injectable preparations in the vial forming a solution before administration.

TreosulfanoZentiva is available in packages with 1 vial or 5 vials.

Vials with or without a retractable plastic wrapper with a protective base (disc). The retractable wrapper is not in contact with the product and provides additional protection during transportation. It also improves safe handling of the product by healthcare professionals.

Marketing Authorization Holder

Zentiva k.s.,

U kabelovny 130,

Praga 10 – Dolní Mecholupy,

102 37 Czech Republic

Responsible for manufacturing

MIAS Pharma Limited

Suite 2, Stafford House, Strand Road

Portmarnock, Co. Dublin

Ireland

Tillomed Malta Limited,

Malta Life Sciences Park,

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000, Malta

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Zentiva Spain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

Spain

This medication is authorized in the member states of the European Economic Area with the following names:

Last review date of thisleaflet:November 2019

The detailed information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

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This information is intended solely for healthcare professionals:

For single use only.

Procedures for handling and disposal of cytotoxic medications:

1. Only trained personnel should reconstitute the solution.
2. A designated preparation area is required.
3. Staff should wear appropriate protective clothing, mask, and gloves.
4. Precautions should be taken to avoid accidental contact of the medication with the eyes. If the solution comes into contact with the skin or eyes, rinse the area immediately with plenty of water or saline solution. A cream may be used to treat temporary skin irritation. In case of eye irritation, contact an ophthalmologist.
5. Pregnant individuals should not handle this medication.
6. Adequate precautions should be taken for the disposal of items used to reconstitute cytotoxic medications (syringes, needles, etc.).
7. The work surface should be covered with disposable plastic and absorbent paper.
8. Use Luer-lock accessories for all equipment and syringes. It is recommended to use large-caliber needles to minimize pressure and the possible formation of aerosols. This can also be reduced by using a venting needle.

Instructions for reconstituting Treosulfano Zentiva

To avoid solubility problems during reconstitution, the following aspects should be considered:

1. The solvent, water for injectable preparations, should be heated to 25 - 30° C using a water bath.

2. Treosulfano should be carefully removed from the inner surface of the infusion vial by agitating.

This procedure is very important, as the humidification of the powder adhering to the surface results in clumping. In case of clumping, the vial should be vigorously shaken.

3. One end of the cannula is placed in the rubber stopper of the water vial, and the other end of the cannula is placed in the treosulfano vial with the opening facing downwards.

Turning the entire system allows the water to enter the lower vial while gently agitating.

Following these instructions, the reconstitution procedure should not take more than 2 minutes. See the diagram below to help with the reconstitution process: