Leaflet: information for the user

Trecondi 1g powder for solution for infusion

Trecondi 5g powder for solution for infusion

treosulfano

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, pharmacist or nurse.
• If you experience any side effects, consult your doctor, pharmacist or nurse,even if they are not listed in this leaflet. See section4.

Trecondicontains the active ingredient treosulfano, which belongs to a group of medications called alkylating agents. Treosulfano is used to prepare patients for a bone marrow transplant (hematopoietic stem cell transplant). Treosulfano destroys cells in the bone marrow and allows the transplant of new cells in the bone marrow to promote the production of healthy blood cells.

Trecondi is used aspre-transplant treatment for hematopoietic stem cell transplantin adults and in adolescents and older children over 1month with cancer and non-cancerous disorders.

Do not administer Trecondi

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

Warnings and precautions

Trecondi is a medication that destroys cells (cytotoxic) used to reduce the number of blood cells. This is the desired effect at the recommended dose. You will have periodic 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 medications, such as antibiotics, antifungals, or antivirals.

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

Since mouth mucosa inflammation is a frequent adverse effect of this medication, 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 menopausal symptoms (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 adverse effects than older children. Your child will be monitored for signs of adverse effects affecting the nerves or respiratory problems.

Dermatitis with perianal ulcers can occur in infants and children wearing diapers because the passage of treosulfan to the urine can damage the skin. Therefore, diapers should be changed frequently during the 6-8 hours following medication administration.

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

Other medications and Trecondi

Inform your doctor if you are taking, have taken recently, or may need to take any other medication, including those purchased without a prescription.

Pregnancy, breastfeeding, and fertility

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

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

You should stop breastfeeding before starting treatment with this medication.

If you are a man receiving treatment with this medication, do not conceive a child during and for 6 months after completing treatment.

This medication may cause sterility and prevent you from becoming pregnant after treatment. If you wish to have children, inform your doctor before starting treatment. Men should seek advice on the possibility of preserving their sperm before starting treatment.

Driving and operating machinery

This medication may cause nausea, vomiting, and dizziness, which may reduce your ability to drive or operate machinery. Do not drive or operate machinery if this happens.

Use in adults

This medicationis used in combination with fludarabina.

The recommended dose is 10‑14g/m² of body surface area (calculated based on weight and height).

Use in children and adolescents

This medication is used in combination with fludarabina and, in most cases, also with tiotepa.The recommended dose is 10‑14g/m² of body surface area.

How Trecondi is administered

A doctor will be responsible for administering this medication. It is administered through an intravenous infusion over 2hours for 3durations before the infusion of hematopoietic stem cells.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects

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

• Decrease in the number of blood cells, which is the expected effect of the medicine to prepare you for pre-transplant perfusion (all patients: very common);
• Infections caused by bacteria, viruses, and fungi (adults: common; children and adolescents: very common);
• Blockage of a vein in the liver (adults: rare; children and adolescents: unknown frequency);
• Pneumonia (inflammation of the lung) (adults: very common).

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

Adults

The following is a list of all other side effects by frequency.

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

• Decrease in white blood cell count 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)

• Bloodstream infection (sepsis);
• Allergic reactions;
• Decreased appetite;
• Difficulty sleeping (insomnia);
• Headache, dizziness;
• Changes and abnormalities in heart rhythm (irregular heartbeat, too fast or too slow);
• High or low blood pressure, redness;
• Difficulty breathing, nasal bleeding;
• Mouth pain, stomach inflammation, stomach discomfort, abdominal pain (abdominal); constipation, difficulty swallowing, stomach pain or esophageal pain;
• A type of rash with flat or raised red bumps on the skin (maculopapular rash), red spots on the skin (purpura), skin redness (erythema), hand-foot syndrome (palms of the hands or soles of the feet become numb, swollen, painful, or red), itching, hair loss;
• Arm or leg pain, back pain, bone pain, joint pain;
• Sudden decrease in kidney function, blood in the urine;
• Fluid retention in the body causing swelling (edema), fever, chills;
• Elevated liver enzymes, increased C-reactive protein (a marker of inflammation in the body), weight gain, weight loss.

Rare(may affect up to 1 in 100 people)

• Abnormal control of blood sugar levels, including high or low blood sugar levels;
• Confusion;
• Brain hemorrhage, nerve problems in the arms or legs with symptoms such as numbness, increased or decreased sensitivity, tingling, and burning (peripheral sensory neuropathy);
• Sensation of spinning (dizziness)
• Hematoma;
• Fluid around the lung (pleural effusion), throat inflammation, laryngeal inflammation, hoarseness;
• Bleeding in the mouth, sensation of swelling, dry mouth;
• A type of rash with red spots and, sometimes, purple areas or blisters on the skin (erythema multiforme), acne, rash, dry skin;
• Muscle pain;
• Pain in the urinary tract;
• Non-cardiac chest pain, pain;
• Elevated blood lactate dehydrogenase (a substance indicating tissue or cellular damage).

Unknown frequency(cannot be estimated from available data)

• Potentially fatal infection of the bloodstream (septic shock);
• Different cancer caused by chemotherapy (secondary malignancy);
• Increased acidity in the blood;
• Abnormal brain function (encephalopathy), restless, repetitive, or involuntary movements, and rapid speech (extrapyramidal disorder), fainting, numbness, tingling, or prickling (paresthesia);
• Dry eye;
• Inadequate blood supply to the heart for the body's needs (heart failure), heart attack, fluid in the sac surrounding the heart (pericardial effusion);
• Blockage of a blood vessel (embolism);
• Throat pain, hoarseness, cough;
• Gastrointestinal bleeding, colon inflammation, esophageal inflammation, anal inflammation;
• Medication-induced liver damage, liver enlargement;
• Skin inflammation (dermatitis), skin tissue death, skin ulcer, skin pigmentation (bronze color);
• Renal insufficiency, urinary tract inflammation with bleeding (hemorrhagic cystitis), painful urination (dysuria);
• Elevated blood lactate dehydrogenase (a substance indicating tissue or cellular damage).

Children and adolescents

The following is a list of all other side effects by frequency.

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

• Inflammation of the mucous membranes (especially in the mouth) with ulcers, diarrhea, nausea, vomiting;
• Liver damage;
• Itching, hair loss;
• Fever;
• Elevated liver enzyme (ALT) in the blood.

Common(may affect up to 1 in 10 people)

• Headache;
• Throat pain, nasal bleeding;
• Difficulty swallowing, anal inflammation, mouth pain;
• Redness or peeling of most of the skin on the body (dermatitis exfoliativa), a type of rash with flat or raised red bumps on the skin (maculopapular rash), rash, redness of the skin (erythema), urticaria, skin pain, skin pigmentation (bronze color);
• Chills;
• Elevated liver enzymes (AST) 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).

Unknown frequency(cannot be estimated from available data)

• Different cancer caused by chemotherapy (secondary malignancy);
• Decrease in white blood cell count with fever (febrile neutropenia);
• Less acidic than normal in the blood (alkalosis), abnormal levels of electrolytes in the blood, decreased magnesium levels in the blood, decreased appetite;
• Seizures, numbness, tingling, or prickling (paresthesia);
• Bleeding in the eye, dry eye;
• Fluid leakage from capillaries (small blood vessels), high blood pressure, low blood pressure;
• Decreased oxygen supply to different parts of the body (hypoxia), cough;
• Colon inflammation, stomach discomfort, rectal inflammation, anal pain, gum pain, esophageal pain, constipation;
• Liver enlargement;
• Skin ulcer, a type of rash with red spots and, sometimes, purple areas or blisters on the skin (erythema multiforme), skin disease with blisters containing fluid (dermatitis bullosa), acne, hand-foot syndrome (palms of the hands or soles of the feet become numb, swollen, painful, or red), diaper dermatitis with ulcers around the anus;
• Arm or leg pain;
• Decreased kidney function, renal insufficiency, urinary tract inflammation (cystitis), blood in the urine;
• Redness of the skin of the scrotum, penile pain;
• Fluid accumulation in tissues causing facial swelling, fatigue, pain;
• Elevated liver enzyme (gamma-glutamyl transferase) in the blood.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a side effect that does not appear in this prospectus.You can also report them directly through the national notification system included in Appendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label and on the box after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

For conservation conditions after reconstitution of the medication, see the information for healthcare professionals below.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications you no longer need. This will help protect the environment.

Composition ofTrecondi

The active ingredient is treosulfan. This medication does not contain any other component.

Trecondi 1g powder for solution for infusion

1vial of powder contains 1g of treosulfan.

Trecondi 5g powder for solution for infusion

1vial of powder contains 5g of treosulfan.

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

Appearance of the product and contents of the package

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

Trecondi is available in packages of 1or 5vials (type I glass).

Only some package sizes may be commercially available.

Marketing authorization holder and responsible manufacturer

medac

Gesellschaft für klinische Spezialpräparate mbH

Theaterstr.6

22880Wedel

Germany

Phone:+49 4103 8006-0

Fax:+49 4103 8006-100

Email:[email protected]

Last review date of this leaflet:11/2023.

Other sources of information

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

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This information is intended solely for healthcare professionals:

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

The medication will be reconstituted by trained personnel. During the handling of treosulfan, inhalation and direct contact with skin or mucous membranes should be avoided (use of disposable protective gloves, glasses, lab coats, and a mask is recommended).The contaminated body parts should be carefully washed with water and soap, while the eyes should be rinsed with sodium chloride 9mg/ml (0.9%) solution. If possible, it is recommended to work in a special safety workbench equipped with a laminar flow cabinet and a disposable absorbent and impermeable tray. Caution and proper measures should be taken to dispose of used disposable materials (syringes, needles, etc.) for cytotoxic medications. Luer-Lock connectors should be used on all syringes and equipment. It is recommended to use large-caliber needles to minimize pressure and the possible formation of aerosols. Aerosols can also be reduced by using a venting needle.

Pregnant healthcare professionals should not handle cytotoxics.

Instructions for reconstituting treosulfan:

1.Treosulfan is reconstituted in its original glass vial. Reconstituted treosulfan solutions can be combined in a larger glass vial, a PVC bag, or a PE bag.

2.To avoid solubility problems, warm the solvent —sodium chloride 4.5mg/ml (0.45%)— to 25°C‑30°C (no higher); for example, in a water bath.

3.Carefully separate the treosulfan powder from the inner surface of the vial by agitating it. This procedure is very important, as the humidification of the powder causes it to stick to the surface and form a cake. If this happens, vigorously agitate the vial to redissolve the cake.

4.Reconstitute each vial of Trecondi containing 1g of treosulfan in 20ml of preheated sodium chloride 4.5mg/ml (0.45%) solution (up to 30°C) by agitating it.

Reconstitute each vial of Trecondi containing 5g of treosulfan in 100ml of preheated sodium chloride 4.5mg/ml (0.45%) solution (up to 30°C) by agitating it.

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

Reconstituted infusion solution

The reconstituted solution contains 50mg of treosulfan per ml and is presented as a transparent and colorless solution.

Solutions showing signs of precipitation should not be used.

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

From a microbiological point of view, unless the reconstitution method excludes the risk of microbial contamination, the medication should be used immediately. If not used immediately, the storage conditions and duration during use are the responsibility of the user.

Do not store the reconstituted solution in the refrigerator (between 2°C and 8°C) as it may precipitate.

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