Treosulfan zentiva

Package leaflet: Information for the user

Treosulfan Zentiva, 5 g, powder for solution for infusion
Treosulfan
Please read all of this leaflet carefully before you are given the medicine because it contains
important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any further questions, please ask your doctor or nurse.
• If you experience any side effects, including any possible side effects not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of the leaflet

1. What Treosulfan Zentiva is and what it is used for
2. What you need to know before being given Treosulfan Zentiva
3. How Treosulfan Zentiva is given
4. Possible side effects
5. How to store Treosulfan Zentiva
6. Contents of the pack and other information

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

Treosulfan Zentiva contains the active substance treosulfan. Treosulfan belongs to a group of anticancer medicines called alkylating agents. These medicines inhibit tumour growth.
Treosulfan Zentiva has been prescribed by your doctor for the treatment of advanced ovarian cancer after at least one prior standard therapy.

2. Important information before using Treosulfan Zentiva

When not to use Treosulfan Zentiva

• if the patient is allergic to treosulfan
• if the patient has too low a number of blood cells (severe bone marrow suppression). Before each administration, the patient will have a blood test to check whether blood cell counts allow for Treosulfan Zentiva to be given
• during breastfeeding.

Warnings and precautions
Before starting treatment with Treosulfan Zentiva, discuss this with your doctor or
nurse:
Bone marrow damage and blood count monitoring
Dose-limiting toxicity of treosulfan is bone marrow suppression, which usually resolves after discontinuation of the drug. Symptoms include reduced numbers of white blood cells (leukocytes) and platelets (thrombocytes), as well as reduced red blood cell count (haemoglobin).
Bone marrow dysfunction is cumulative; therefore, the doctor will monitor blood counts at shorter intervals, starting from the 3rd treatment cycle. This is particularly important when Treosulfan Zentiva is used in combination with other treatments affecting bone marrow, such as radiotherapy. If bone marrow function is impaired, there is an increased risk of infection.
White blood cell (leukocyte) and platelet (thrombocyte) counts usually return to baseline values within 28 days.
Lung toxicity
Breathing difficulties, cough or high fever may indicate lung disease.
Treatment with treosulfan should be discontinued in case of severe lung function impairment, such as inflammation, fibrosis or infections.
When using Treosulfan Zentiva, the patient should be aware of:

• increased risk of developing certain types of infections;
• possible development of various blood cancers after long-term treatment;
• since treosulfan is excreted by the kidneys, blood counts should be closely monitored and the dose appropriately adjusted if the patient develops impaired kidney function;
• anticancer treatment may increase the risk of systemic infection following certain vaccinations. Therefore, this medicine should not be used together with vaccines containing live microorganisms;
• due to the possibility of developing cystitis, more frequent urination or urinary urgency, with or without blood in the urine (haemorrhagic cystitis), it is recommended to drink more fluids than usual for up to 24 hours after treosulfan treatment;
• for women of childbearing potential, effective contraception (e.g. contraceptive agents) must also be used during treatment and for six months after its completion (see section "Pregnancy and breastfeeding").

Extravasation
Correct infusion technique must be used during administration of Treosulfan Zentiva, as leakage of the treosulfan solution outside the blood vessel into surrounding tissues may lead to local, painful inflammatory reactions. If extravasation occurs, the infusion must be stopped immediately and the remaining dose administered into another vein.
Treosulfan Zentiva and other medicines
Inform your doctor or nurse about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription. This also applies to herbal medicines.
The effect of ibuprofen or chloroquine may be reduced when administered concomitantly with Treosulfan Zentiva.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine. There are no data or only limited data on the use of Treosulfan Zentiva 5 g powder for solution for infusion in pregnant or breastfeeding women.
Pregnancy
Since fetal harm cannot be excluded, Treosulfan Zentiva 5 g powder for solution for infusion should not be used during pregnancy unless the physician considers it absolutely necessary. Pregnancy must be avoided during treatment with Treosulfan Zentiva 5 g powder for solution for infusion.
If pregnancy occurs during treatment with Treosulfan Zentiva 5 g powder for solution for infusion, the physician must be informed immediately.
Contraception in women
Women of childbearing potential must use effective contraception during treatment with Treosulfan Zentiva 5 g powder for solution for infusion and for six months after completion of treatment.
Breastfeeding
Since transfer of the substance into breast milk cannot be excluded, breastfeeding must not be undertaken during treatment with Treosulfan Zentiva 5 g powder for solution for infusion.
Driving and operating machinery
Studies on the effect on the ability to drive vehicles and operate machinery have not been conducted. If nausea or vomiting occurs, ability to drive vehicles and operate machinery may be impaired. If such symptoms occur, the patient should not drive or operate machinery.

3. How to use Treosulfan Zentiva

Treosulfan Zentiva will be administered by a doctor or nurse as an intravenous infusion.
This will take between 15 and 30 minutes (intravenous infusion), and the dose will be calculated
specifically for the patient by the doctor.
The doctor will calculate the required dose of Treosulfan Zentiva based on the patient's blood morphology. The doctor
may reduce the dose if the patient has received other anticancer drugs or radiotherapy. The dose the patient receives also depends on the patient's body size and varies according to body surface area (BSA). During treatment with Treosulfan Zentiva, infusions are usually given every 3 to 4 weeks. Generally, 6 treatment cycles are administered.
The doctor may adjust the dose and frequency depending on blood test results, the patient's general health, other therapies the patient is receiving, and the patient's response to treatment with Treosulfan Zentiva. If you have any doubts regarding the treatment, please consult your doctor or nurse.
If the patient experiences pain at the site of administration, inform the doctor or nurse immediately.
Use in children
Use of this medicine is not recommended in children.
Use of a higher than recommended dose of Treosulfan Zentiva
If the patient receives too high a dose of this medicine, they may become ill or develop reduced blood cell counts. The doctor may administer blood transfusions or take other necessary measures.
If you have any further questions about the use of 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.
Your doctor will discuss these with you and explain the risks and benefits of treatment.
You should inform your doctor or nurse immediately if any of the following symptoms occur:

• Allergic reactions [rare (may occur in up to 1 in 1,000 patients)]: if you experience itching, rash, swelling of the face, lips, tongue and/or throat, which may cause difficulty swallowing or breathing, or a drop in blood pressure.
• Fever or infection [very common (may occur in more than 1 in 10 patients)]: if you have a fever of 38°C or higher, sweating, or signs of infection (because your white blood cell count may be lower than usual).
• Weakness [very common (may occur in more than 1 in 10 people)], shortness of breath or pale skin (because your red blood cell count may be lower than usual).
• Bleeding [very common (may occur in more than 1 in 10 people)] from the gums, mouth or nose, or unexpected bruising or pale skin (because your platelet count may be lower than usual).
• Breathing difficulties [very rare (may occur in up to 1 in 10,000 patients)] (because you may experience an allergic reaction, inflammation or infection of the lungs).

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

• Decrease in white blood cells (increases the risk of infection), platelets (may cause bruising and bleeding from gums, mouth and nose), and red blood cells (may cause paleness, weakness and shortness of breath) – therefore, regular blood count monitoring is necessary.
• Gastrointestinal disturbances, including nausea (feeling sick), with or without vomiting.
• Mild hair loss. Hair growth should return to normal after treatment.
• Brown discoloration of the skin.

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

• Infections caused by bacteria, viruses or fungi (may lead to fever, sweating and general malaise).
• Gastrointestinal disorders.

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

• Various blood cancers (after long-term treatment).
• Inflammation of the mucous membrane of the mouth (stomatitis).

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

• Severe reduction in all blood cell types (pancytopenia); may cause weakness and bruising, and increases the risk of infection.
• Addison's disease, a condition involving adrenal gland dysfunction, leading to brown skin pigmentation, gastrointestinal disturbances, low blood pressure (feeling faint), and general weakness.
• Sweating, tremor and hunger due to low blood glucose levels (hypoglycaemia).
• Tingling and numbness (paraesthesia).
• Weakening of the heart muscle due to structural changes (cardiomyopathy).
• Shortness of breath (lung inflammation and fibrosis, and lung infections).
• Increased liver function test values (may lead to fatigue, feeling of pressure in the upper right abdomen, and yellowish discoloration of the sclera and skin).
• Hives (rash) or itchy rash; skin inflammation with or without peeling (scleroderma and psoriasis), skin redness (erythema).
• Bladder inflammation causing pain, more frequent urination and a feeling of urgency, with or without blood in the urine (haemorrhagic cystitis).
• Malaise (flu-like symptoms).
• Painful redness or swelling at the injection site (in case of treosulfan solution leakage into surrounding tissues).

Frequency not known: frequency cannot be estimated from the available data:

• Blood infection (sepsis).

You should inform your doctor or nurse immediately if any of the above symptoms occur.
Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, tell your doctor or nurse.
Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
PL-02 222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Treosulfan Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and the outer carton after: EXP. The expiry date refers to the last day of the stated month.
Do not store the reconstituted medicine in the refrigerator (2–8°C), as this may cause precipitation. Do not use solutions in which a precipitate has formed.
Do not store in the refrigerator.
Chemical and physical in-use stability has been demonstrated for 12 hours at 30°C. From a microbiological point of view, unless the reconstitution method excludes the risk of microbiological contamination, the medicine should be used immediately. If not used immediately, the responsibility for the storage duration and conditions during use lies with the user.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Treosulfan Zentiva contains

• The active substance is treosulfan. Each vial contains 5 g of treosulfan.
• After reconstitution, 1 ml of solution contains 50 mg of treosulfan.

What Treosulfan Zentiva looks like and contents of the pack
Treosulfan Zentiva is a white, crystalline, lyophilized powder or powder supplied in clear type I glass vials; each vial contains 5 g of treosulfan.
Prior to administration, the dry powder is mixed with water for injections in the vial to form a solution.
Treosulfan Zentiva is available in cardboard packs containing 1 vial or 5 vials.
The vials may, but do not necessarily, be placed in a shrink-wrapped plastic sleeve/made with a base of this material (base support). The plastic sleeve does not come into contact with the medicine and provides additional protection during transport. This facilitates safe handling of the medicine for both healthcare and pharmaceutical personnel.

Marketing Authorisation Holder
Zentiva, k.s.
U kabelovny 130
Dolní Měcholupy
102 37, Prague 10
Czech Republic

Importer
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

For further information on this medicine, contact the local representative of the Marketing Authorisation Holder:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
Tel. +48 22 375 92 00

This medicine is authorised for marketing in the European Economic Area countries under the following names:
Germany: Treosulfan Tillomed 5g Pulver zur Herstellung einer Infusionslösung
France: Treosulfan Tillomed 5g poudre pour solution pour perfusion
Spain: Treosulfano Tillomed 5g polvo para solución para perfusión
EFG
Austria: Treosulfan Tillomed 5g Pulver zur Herstellung einer Infusionslösung
Czech Republic: Treosulfan Tillomed
Greece: Treosulfan Tillomed 5g κόνις για διάλυμα προς έγχυση
Poland: Treosulfan Zentiva
Romania: Treosulfan Tillomed 5g Pulbere pentru soluţie perfuzabilă
Denmark: Treosulfan Tillomed
Finland: Treosulfan Tillomed infuusiokuiva-aine liuosta varten 5g
Norway: Treosulfan Tillomed 5g Pulver til infusjonsvæske, oppløsning
Sweden: Treosulfan Tillomed 5g Pulver till infusionsvätska, lösning
Belgium: Treosulfan Tillomed 5g Poeder voor oplossing voor infusie / Treosulfan Tillomed 5g poudre pour solution pour perfusion / Treosulfan Tillomed 5g Pulver zur Herstellung einer Infusionslösung
Ireland: Treosulfan Tillomed 5g powder for solution for infusion
Netherlands: Treosulfan Tillomed 5g Poeder voor oplossing voor infusie
Portugal: Treossulfano Tillomed 5g pó para solução para perfusão

Information intended exclusively for healthcare professionals:

For single use only.
Guidelines for safe handling of cytotoxic drugs:

1. Reconstitution of the medicinal product should be carried out by trained healthcare professionals.
2. This should be performed in a designated area.
3. Protective gloves, masks, and protective clothing must be worn.
4. Precautions should be taken to avoid accidental contact of the medicinal product with the eyes. In case of accidental contact of the solution with skin or eyes, the contaminated area should be rinsed immediately with large amounts of water or normal saline solution. A mild cream may be used to relieve transient skin irritation. In case of eye contact, medical advice should be sought.
5. Personnel who may be pregnant must not handle cytotoxic agents.
6. Appropriate care and precautions must be taken when disposing of materials (syringes, needles, etc.) used during reconstitution of cytotoxic drugs.
7. The work surface should be covered with a disposable plastic-backed absorbent pad.
8. Luer-Lock fittings must be used on all syringes and sets. Use of large-bore needles is recommended to minimize pressure and the risk of aerosol formation. This risk can also be reduced by using a vented needle.

Instructions for reconstitution of Treosulfan Zentiva medicinal product
To avoid solubility issues during reconstitution, the following aspects should be considered:

1. The solvent, water for injections, must be warmed to 25–30°C (not higher) in a water bath.
2. Treosulfan should be carefully dislodged from the inner surface of the infusion vial by gentle shaking. This step is very important, as wetting the powder may cause it to adhere to the vial walls, leading to clumping. If clumping occurs, the vial should be shaken vigorously for a prolonged period.
3. One end of a double-ended cannula should be inserted into the rubber stopper of the vial containing water for injections. The vial containing treosulfan should then be attached to the other end of the cannula, with its bottom facing upwards. The entire assembly should then be inverted. While gently shaking the vial, the water flows into the lower vial. If these instructions are followed correctly, the entire reconstitution process should not take longer than 2 minutes. The diagram below facilitates the reconstitution procedure.