TRECONDI 5 G POWDER FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Trecondi 1g powder for solution for infusion

Trecondi 5g powder for solution for infusion

treosulfan

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

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What is Trecondi and what is it used for
2. What you need to know before you are given Trecondi
3. How to use Trecondi
4. Possible side effects
5. Storage of Trecondi
6. Contents of the pack and other information

1. What is Trecondi and what is it used for

Trecondi contains the active substance treosulfan, which belongs to a group of medicines called alkylating agents. Treosulfan is used to prepare patients for a bone marrow transplant (haematopoietic stem cell transplantation). Treosulfan destroys the cells in the bone marrow and allows the transplant of new cells into the bone marrow to promote the production of healthy blood cells.

Trecondi is used as pre-treatment before haematopoietic stem cell transplantationin adults and in adolescents and children over 1 month with cancer and non-cancerous disorders.

2. What you need to know before you are given Trecondi

You should not be given Trecondi

• if you are allergic to treosulfan;
• if you have an uncontrolled active infection;
• if you have severe heart, lung, liver, or kidney disease;
• if you have a hereditary DNA repair disorder, a disease that reduces the ability to repair DNA (which carries your genetic information);
• if you are pregnant or think you may be pregnant.

Warnings and precautions

Trecondi is a cell-destroying (cytotoxic) medicine used to reduce the number of blood cells. This is the desired effect at the recommended dose. You will have regular blood tests during treatment to check that your blood cell counts are not too low.

To prevent and treat infections, you will be given certain medicines, such as antibiotics, antifungals, or antivirals.

Trecondi may increase the risk of developing another cancer in the future.

Since inflammation of the mouth mucosa is a common side effect of this medicine, you should pay special attention to your oral hygiene. Preventive measures such as the use of mouthwashes (e.g., with barrier protectors, antibiotics) or the application of ice inside the oral cavity (reduces blood flow to the mouth mucosa and reduces the amount of treosulfan that reaches the cells) are recommended.

You should not receive live vaccines during treatment with treosulfan.

Trecondi may cause symptoms of menopause (absence of menstruation).

Children and adolescents

Very rarely, seizures (convulsions) can occur in infants under 4 months. Children under 1 year may experience more severe respiratory side effects than older children. Your child will be monitored for signs of side effects that affect the nerves or respiratory problems.

Diaper dermatitis with ulcers in the area around the anus (perianal) can occur in infants and children who wear diapers because the passage of treosulfan into the urine can damage the skin. Therefore, diapers should be changed frequently during the 6-8 hours following administration of the medicine.

There is not enough information about the use of treosulfan in children under 1 month.

Other medicines and Trecondi

Tell your doctor if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

Pregnancy, breastfeeding, and fertility

You should not become pregnant during treatment with this medicine and until 6 months after treatment. Use an effective contraceptive method while you or your partner are receiving this medicine.

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

You should stop breastfeeding before starting treatment with this medicine.

If you are a man receiving treatment with this medicine, you should not father a child during and until 6 months after treatment.

This medicine may cause infertility and prevent you from becoming pregnant after treatment. If you want to have children, you should discuss this with your doctor before starting treatment. Men should seek advice on the possibility of preserving their sperm before starting treatment.

Driving and using machines

This medicine may cause nausea, vomiting, and dizziness, which can reduce your ability to drive or use machines. Do not drive or use machines if you experience these effects.

3. How to use Trecondi

Use in adults

This medicine is used in combination with fludarabine.

The recommended dose is 10-14 g/m² of body surface area (calculated according to weight and height).

Use in children and adolescents

This medicine is used in combination with fludarabine and, in most cases, also with thiotepa. The recommended dose is 10-14 g/m² of body surface area.

How Trecondi is administered

A doctor will administer this medicine to you. It is given by infusion (drip) into a vein over 2 hours over 3 days before the infusion of haematopoietic stem cells.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

The most serious side effects of treatment with treosulfan or transplantation are:

• reduction in the number of blood cells, which is the expected effect of the medicine to prepare you for transplantation (all patients: very common);
• infections caused by bacteria, viruses, and fungi (adults: frequent; children and adolescents: very frequent);
• blockage of a vein in the liver (adults: uncommon; children and adolescents: frequency not known);
• inflammation of the lung (pneumonia) (adults: very common).

Your doctor will monitor your blood cell counts and liver enzymes regularly to detect and treat these events.

Adults

The following is a list of other side effects with their frequencies.

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

• reduction in the number of white blood cells with fever (febrile neutropenia);
• inflammation of the mucous membranes (especially in the mouth) with ulcers, diarrhea, nausea, vomiting;
• fatigue;
• elevated bilirubin in the blood (a liver pigment, often a sign of liver problems).

Common(may affect up to 1 in 10 people)

• infection of the bloodstream (sepsis);
• allergic reactions;
• decreased appetite;
• difficulty sleeping (insomnia);
• headache, dizziness;
• changes and abnormalities in heart rhythm (the heartbeat is irregular, too fast, or too slow);
• high or low blood pressure, flushing;
• difficulty breathing, nosebleeds;
• mouth pain, stomach inflammation, stomach upset, abdominal pain; constipation, difficulty swallowing, stomach or esophagus pain;
• a type of rash with flat or raised red patches on the skin (maculopapular rash), red spots on the skin (purpura), skin redness (erythema), syndrome of hands and feet (the palms of the hands or soles of the feet have tingling, numbness, swelling, and pain, or redness), itching, hair loss;
• arm or leg pain, back pain, bone pain, joint pain;
• sudden decrease in kidney function, blood in urine;
• fluid retention in the body that causes swelling (edema), fever, chills;
• elevated liver enzymes, elevated C-reactive protein (a marker of inflammation in the body), weight gain, weight loss.

Uncommon(may affect up to 1 in 100 people)

• abnormal control of blood sugar levels, including high or low blood sugar levels;
• confusion;
• bleeding in the brain, nerve problems in the arms or legs with symptoms such as numbness, increased or decreased sensitivity, tingling, and burning (peripheral sensory neuropathy);
• feeling of spinning (vertigo)
• bruising;
• fluid around the lung (pleural effusion), throat inflammation, larynx inflammation or pain, hiccups;
• bleeding in the mouth, feeling of swelling, dry mouth;
• a type of rash with red spots and sometimes with purple or blistered areas in the center (erythema multiforme), acne, rash, dry skin;
• muscle pain;
• pain in the urinary tract;
• chest pain not related to heart problems, pain;
• elevated alkaline phosphatase in the blood (your doctor will check this parameter).

Frequency not known(cannot be estimated from the available data)

• potentially life-threatening disease after bloodstream infection (septic shock);
• cancer caused by chemotherapy (secondary malignant neoplasm);
• increased acidity in the blood;
• abnormal brain function (encephalopathy), restless, repetitive, or involuntary movements and rapid speech (extrapyramidal disorder), fainting, feeling of tingling, itching, or numbness (paresthesia);
• dry eye;
• insufficient blood pumping by the heart to meet the body's needs (heart failure), heart attack, fluid in the sac surrounding the heart (pericardial effusion);
• blockage of a blood vessel (embolism);
• sore throat, hoarseness, cough;
• gastrointestinal bleeding, colon inflammation, esophagus inflammation, anus inflammation;
• drug-induced liver injury, enlarged liver;
• skin inflammation (dermatitis), skin tissue death, skin ulcers, bronze-like skin discoloration;
• kidney failure, bladder inflammation with bleeding (hemorrhagic cystitis), pain during urination (dysuria);
• elevated lactate dehydrogenase in the blood (a substance that indicates tissue or cellular damage).

Children and adolescents

The following is a list of other side effects with their frequencies.

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

• mucous membrane inflammation (especially in the mouth) with ulcers, diarrhea, nausea, vomiting, abdominal pain;
• liver damage;
• itching, hair loss;
• fever;
• elevated ALT (a liver enzyme) in the blood.

Common(may affect up to 1 in 10 people)

• headache;
• sore throat, nosebleeds;
• difficulty swallowing, anus inflammation, mouth pain;
• redness or peeling of most of the body skin (exfoliative dermatitis), a type of rash with flat or raised red patches on the skin (maculopapular rash), rash, skin redness (erythema), hives, skin pain, bronze-like skin discoloration;
• chills;
• elevated AST (a liver enzyme) and bilirubin (a liver pigment, often a sign of liver problems) in the blood, elevated C-reactive protein (a marker of inflammation in the body).

Frequency not known(cannot be estimated from the available data)

• cancer caused by chemotherapy (secondary malignant neoplasm);
• reduction in the number of white blood cells with fever (febrile neutropenia);
• less acid than normal in the blood (alkalosis), abnormal electrolyte levels in the blood, decreased magnesium levels in the blood, decreased appetite;
• seizures, feeling of tingling, pinching, or numbness (paresthesia);
• eye bleeding, dry eye;
• leakage of fluid from the small blood vessels (capillaries), high blood pressure, low blood pressure;
• reduced oxygen supply to different parts of the body (hypoxia), cough;
• colon inflammation, stomach upset, rectum inflammation, gum pain, esophagus pain, constipation;
• enlarged liver;
• skin ulcers, a type of rash with red spots and sometimes with purple or blistered areas in the center (erythema multiforme), blistering skin disease (bullous dermatitis), acne, syndrome of hands and feet (the palms of the hands or soles of the feet have tingling, numbness, swelling, and pain, or redness), diaper dermatitis with ulcers in the area around the anus;
• arm or leg pain;
• decreased kidney function, kidney failure, bladder inflammation (cystitis), blood in urine;
• redness of the scrotum skin, penile pain;
• fluid accumulation in the tissues that causes swelling of the face, fatigue, pain;
• elevated liver enzyme (gamma-glutamyl transferase) in the blood.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Trecondi

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date is the last day of the month shown.

No special storage conditions are required.

For the storage conditions after reconstitution of the medicinal product, see the information for healthcare professionals below.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition ofTrecondi

The active ingredient is treosulfan. This medicinal product does not contain any other components.

Trecondi 1 g powder for solution for infusion

1 vial of powder contains 1 g of treosulfan.

Trecondi 5 g powder for solution for infusion

1 vial of powder contains 5 g of treosulfan.

After reconstitution, 1 ml of solution contains 50 mg of treosulfan.

Appearance and Container Contents of the Product

White crystalline powder in a glass vial with a rubber stopper and an aluminum sealing cap.

Trecondi is available in packs of 1 or 5 vials (Type I glass).

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

medac

Gesellschaft für klinische Spezialpräparate mbH

Theaterstr. 6

22880 Wedel

Germany

Tel.: +49 4103 8006-0

Fax: +49 4103 8006-100

E-mail: contact@medac.de

Date of Last Revision of this Leaflet:11/2023.

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.

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This information is intended exclusively for healthcare professionals:

As with all cytotoxic substances, adequate precautions should be taken when handling treosulfan.

The medicinal product will be reconstituted by trained personnel. When handling treosulfan, inhalation and direct contact with skin or mucous membranes should be avoided (the use of suitable disposable protective gloves, goggles, gowns, and masks is recommended). Contaminated body parts should be carefully rinsed with water and soap, while eyes should be rinsed with sodium chloride 9 mg/ml (0.9%) solution. If possible, it is recommended to work on a special safety workbench equipped with a laminar flow cabinet and a disposable absorbent and impermeable sheet. Caution is recommended, and adequate measures should be taken to dispose of disposable materials (syringes, needles, etc.) used to reconstitute cytotoxic medicinal products. Luer-Lock connectors should be used on all syringes and equipment. The use of large-caliber needles is recommended to minimize pressure and potential aerosol formation. Aerosols can also be reduced by using a vented needle.

Pregnant healthcare professionals should not handle cytotoxics.

Instructions for the reconstitution of treosulfan:

1. Treosulfan is reconstituted in its original glass vial. The reconstituted treosulfan solutions can be combined in a larger glass vial, a polyvinyl chloride (PVC) bag, or a polyethylene (PE) bag.
2. To avoid solubility problems, warm the solvent — sodium chloride 4.5 mg/ml (0.45%) solution — to 25°C-30°C (not above); for example, in a water bath.
3. Carefully separate the treosulfan powder from the inner surface of the vial by shaking. This procedure is very important, as moistening the powder causes it to stick to the surface and become lumpy. If this happens, shake the vial vigorously to redissolve the cake.
4. Reconstitute each vial of Trecondi containing 1 g of treosulfan in 20 ml of preheated sodium chloride 4.5 mg/ml (0.45%) solution (at a maximum of 30°C) by shaking.

Reconstitute each vial of Trecondi containing 5 g of treosulfan in 100 ml of preheated sodium chloride 4.5 mg/ml (0.45%) solution (at a maximum of 30°C) by shaking.

To prepare the sodium chloride 4.5 mg/ml (0.45%) solution, equal volumes of sodium chloride 9 mg/ml (0.9%) solution and water for injections can be mixed.

Reconstituted Infusion Solution

The reconstituted solution contains 50 mg of treosulfan per ml and appears as a clear and colorless solution.

Solutions showing signs of precipitation should not be used.

After reconstitution with sodium chloride 4.5 mg/ml (0.45%) solution, chemical and physical stability has been demonstrated for 3 days at 25°C.

From a microbiological point of view, unless the method of reconstitution precludes the risk of microbial contamination, the medicinal product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user.

The reconstituted solution should not be stored in the refrigerator (between 2°C and 8°C) as it may precipitate.

Treosulfan has mutagenic and carcinogenic potential. The remnants of the medicinal product and the materials used for reconstitution and administration should be disposed of according to the usual procedures applicable to antineoplastics, respecting the current regulations on the disposal of hazardous waste.