TRECONDI 50 mg /Ml Powder For Intravenous Infusion Solution

Зміст інструкції

1. Trecondi 1 g powder for solution for infusion, 5 g powder for solution for infusion
   1. What is Trecondi and what is it used for
   2. What you need to know before you receive Trecondi
   3. How to use Trecondi
   4. Possible side effects
   5. How to store Trecondi
   6. Contents of the pack and other information

Trecondi 1 g powder for solution for infusion, 5 g powder for solution for infusion

treosulfan

Read this leaflet carefully before using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If any side effects occur, including those not listed in this leaflet, ask your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

• 1. What Trecondi is and what it is used for
• 2. What you need to know before you receive Trecondi
• 3. How to use Trecondi
• 4. Possible side effects
• 5. How to store 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 bone marrow transplantation (hematopoietic
stem cell transplantation). Treosulfan destroys bone marrow cells and allows the
transplantation of new bone marrow cells, leading to the production of healthy blood cells.
Trecondi is used as a treatment before hematopoietic stem cell transplantationin adults
and adolescents and children over one month of age with cancer and non-cancerous diseases.

2. What you need to know before you receive Trecondi

Trecondi must not be administered to you

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

Warnings and precautions
Trecondi is a medicine that kills cells (cytotoxic), used to reduce the number of blood
cells. At the recommended dose, this is the desired effect. You will undergo periodic blood
tests during treatment to check that the number of blood cells does not decrease
excessively.
For the prevention and treatment of infections, you will be given medicines such as
antimycotics, antifungals or antivirals.
Trecondi may increase the risk of developing another tumor in the future.
Since inflammation of the oral mucosa is a common side effect of this medicine,
attention should be paid to adequate oral hygiene. Preventive measures are recommended, such as the use
of mouthwashes (e.g. with barrier-effect protectives, antimicrobials) or the application of ice
inside the oral cavity (reduces blood flow to the oral mucosa and reduces the amount of treosulfan
reaching the cell).
You must not receive live vaccines during treatment with treosulfan.
Trecondi may cause menopausal symptoms (cessation of menstruation).

Children and adolescents
Seizures (convulsions) may occur very rarely in infants under 4 months of age. Children
under 1 year of age may have more serious side effects affecting
breathing, compared to older children. The child will be monitored for signs of side effects affecting the
nerves and breathing problems.
Diaper rash with ulcers around the anus (perianal) may occur in infants and
children wearing diapers because treosulfan excreted in the urine can damage the skin.
Therefore, diapers should be changed frequently during the 6-8 hours after each dose of this
medicine.
There is insufficient information on the use of treosulfan in children under 1 month of age.

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

Pregnancy, breastfeeding and fertility
You must not become pregnant during treatment with this medicine and for a period of up to
6 months after treatment. Use an effective method of contraception when you or your partner are
being treated with this medicine.
If you are pregnant, suspect you are pregnant, are planning a pregnancy or are breastfeeding
with breast milk, ask your doctor for advice before receiving this medicine.
You must stop breastfeeding before starting treatment with this medicine.
If you are a man and are being treated with this medicine, you must not father a child during and up to
6 months after treatment.
This medicine may cause infertility and it may not be possible to become pregnant after the
treatment. If you wish to have children, discuss this with your doctor before treatment. Men should
seek advice on the possibility of storing sperm before starting therapy.

Driving and operating machinery
This medicine may cause nausea, vomiting and dizziness, with a possible reduction in the ability to
drive vehicles or operate machinery. If you experience these symptoms, do not drive vehicles and do not use
machinery.

3. How to use Trecondi

Use in adults
This medicine is used in association with fludarabine.
The recommended dose is 10-14 g/m² of body surface area (calculated using height and weight).

Use in children and adolescents
This medicine is used in association 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
This medicine will be administered by your doctor. Administration is via intravenous
infusion over 2 hours for 3 days before stem cell blood infusion.

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 therapy with treosulfan or the transplant procedure
include:

• reduction in the number of blood cells, which is the expected effect of the medicine in order to prepare it for the transplant infusion (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: uncommon; children and adolescents: frequency not known)
• inflammation of the lungs (pneumonia) (adults: uncommon)

The doctor will regularly check the number of blood cells and liver enzymes, to detect
and manage these events.
Adults
A list of all other side effects is given below according to their frequency.

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 lining of various parts of the body, especially inside the mouth (which can cause ulcers), diarrhoea, nausea, vomiting
• fatigue
• increased level of bilirubin (a liver pigment, which often signals problems with this organ) in the blood

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 rate (irregular, too fast or too slow heartbeat)
• high or low blood pressure, flushing
• difficulty breathing, nosebleeds
• mouth pain, inflammation of the stomach, stomach discomfort, abdominal pain, constipation, difficulty swallowing, pain in the esophagus or stomach
• type of rash with flat red lesions or raised red bumps (maculopapular rash), red spots on the skin (purpura), skin redness (erythema), hand-foot syndrome (tingling, numbness, painful swelling or redness of the palms of the hands or soles of the feet), 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
• increased liver enzymes, increased 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, problems with the nerves in the arms or legs, with symptoms such as numbness, decreased or increased sensitivity, tingling, burning (peripheral sensory neuropathy)
• feeling of dizziness (vertigo)
• bruising
• fluid around the lungs (pleural effusion), inflammation of the throat, inflammation or pain in the larynx, hiccups
• bleeding in the mouth, feeling of swelling, dry mouth
• type of rash with red spots and sometimes purple areas or blisters in the center (erythema multiforme), acne, rash, dry skin
• muscle pain
• pain in the urinary tract
• chest pain not due to heart problems, pain
• increased levels of alkaline phosphatase in the blood (will be checked by the doctor)

Not known(frequency cannot be estimated from available data)

• potentially life-threatening illness following bloodstream infection (septic shock)
• different tumor caused by chemotherapy treatment (secondary malignant tumor)
• increased acidity in the blood
• abnormal brain function (encephalopathy), restless, repetitive or involuntary movements and rapid speech (extrapyramidal disorder), fainting, sensation of tingling, prickling or numbness (paresthesia)
• dry eye
• heart’s inability to pump enough blood for 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, inflammation of the colon, inflammation of the esophagus, inflammation of the anus
• liver damage caused by medicines, enlarged liver
• inflammation of the skin (dermatitis), death of skin tissue, skin ulcer, bronze pigmentation of the skin
• kidney failure, inflammation of the urinary bladder with bleeding (hemorrhagic cystitis), pain when urinating (dysuria)
• increased level of lactate dehydrogenase (a substance that indicates tissue or cell damage) in the blood

Children and adolescents
A list of all other side effects is given below according to their frequency.

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

• inflammation of the mucous membrane especially inside the mouth (with ulcers), diarrhoea, nausea, vomiting, abdominal pain
• liver damage
• itching, hair loss
• fever
• increased level of a liver enzyme (ALT) in the blood

Common(may affect up to 1 in 10 people)

• headache
• sore throat, nosebleeds
• difficulty swallowing, inflammation of the anus, mouth pain
• redness and scaling of most of the skin of the body (exfoliative dermatitis), type of rash with flat red lesions or raised red bumps (maculopapular rash), rash, skin redness (erythema), hives, skin pain, bronze pigmentation of the skin
• chills
• increased level of a liver enzyme (AST) and bilirubin (a liver pigment, which often signals problems with this organ) in the blood, increased C-reactive protein (a marker of inflammation in the body)

Not known(frequency cannot be estimated from available data)

• different tumor caused by chemotherapy treatment (secondary malignant tumor)
• reduction in the number of white blood cells with fever (febrile neutropenia)
• lower than normal acid in the blood (alkalosis), abnormal electrolyte levels in the blood, decreased magnesium levels in the blood, decreased appetite
• seizures, sensation of tingling, prickling or numbness (paresthesia)
• bleeding in the eye, dry eye
• loss of fluids from capillaries (small blood vessels), high blood pressure, low blood pressure
• reduced oxygen supply to parts of the body (hypoxia), cough
• inflammation of the colon, stomach upset, inflammation of the lining of the rectum, gum pain, esophageal pain, constipation
• enlarged liver
• skin ulcer, type of rash with red spots and sometimes purple areas or blisters in the center (erythema multiforme), skin disease with fluid-filled blisters (bullous dermatitis), acne, hand-foot syndrome (tingling, numbness, painful swelling or redness of the palms of the hands or soles of the feet), diaper rash with ulceration in the area around the anus
• arm or leg pain
• reduced kidney function, kidney failure, inflammation of the urinary bladder (cystitis), blood in the urine
• redness of the skin of the scrotum, pain in the penis
• accumulation of fluids in the tissues causing swelling of the face, fatigue, pain
• increased level of a liver enzyme in the blood (gamma-glutamyl transferase)

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed
in this leaflet. You can also report side effects directly through the national reporting system listed in Annex V. By
reporting side effects you can help provide more information on the safety of this medicine.

5. How to store 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 blister and the carton after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any particular storage conditions.
For storage conditions after reconstitution see the following information intended for
healthcare professionals.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Trecondi contains
The active ingredient is treosulfan. The medicine 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.

Description of the appearance of Trecondi and contents of the pack
White crystalline powder in a glass vial with a rubber stopper and an aluminum crimp cap.
Trecondi is available in packs containing 1 or 5 vials (type I glass).
Not all pack sizes may be marketed.

Marketing authorisation 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: [email protected]

Other sources of information
More detailed information on this medicine is available on the European Medicines Agency website, http://www.ema.europa.eu . Additionally, links to other websites on rare diseases and related therapeutic treatments are provided.
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The following information is intended exclusively for healthcare professionals:
As with all cytotoxic substances, appropriate precautions must be taken when handling treosulfan.
The medicine must be prepared by personnel with adequate training. When handling treosulfan, inhalation, skin contact or contact with mucous membranes should be avoided (the use of appropriate disposable gloves, goggles, gown and protective mask is recommended). Contaminated body parts must be thoroughly rinsed with water and soap, and eyes must be rinsed with 9 mg/mL (0.9%) sodium chloride solution. If possible, it is recommended to work on a dedicated safety workbench equipped with a laminar flow and disposable liquid-proof absorbent film. Disposal of items (syringes, needles, etc.) used to reconstitute cytotoxic medicines requires caution and appropriate precautions.
Use Luer-lock fittings on all syringes and infusion sets. The use of large-gauge needles is recommended to minimize pressure and the potential formation of aerosols. Aerosol formation can be reduced by using a vented needle.
Pregnant personnel should be excluded from handling cytotoxic agents.
Instructions for reconstitution of treosulfan:

• 1. Treosulfan is reconstituted in its original glass container. Reconstituted solutions of treosulfan can be combined in a larger glass vial, a PVC bag or a PE bag.
• 2. To avoid solubility problems, heat the solvent, 4.5 mg/mL (0.45%) sodium chloride solution, to 25 °C-30 °C (not higher), for example using a water bath.
• 3. Carefully remove treosulfan powder from the inner surface of the vial by shaking. This procedure is very important, because wetting of the powder adhering to the surface causes the formation of clumps. If this happens, shake the vial vigorously to redissolve the clumps.
• 4. Reconstitute each vial of Trecondi containing 1 g of treosulfan in 20 mL of pre-heated 4.5 mg/mL (0.45%) sodium chloride solution (maximum 30 °C), by shaking. Reconstitute each vial of Trecondi containing 5 g of treosulfan in 100 mL of pre-heated 4.5 mg/mL (0.45%) sodium chloride solution (maximum 30 °C), by shaking.

To prepare 4.5 mg/mL (0.45%) sodium chloride solution, equivalent volumes of 9 mg/mL (0.9%) sodium chloride solution and water for injections can be mixed.
Reconstituted solution for infusion
The reconstituted solution contains 50 mg of treosulfan per mL and appears as a clear, colorless solution.
Solutions showing signs of precipitation must not be used.
After reconstitution with 4.5 mg/mL (0.45%) sodium chloride solution, chemical and physical stability has been demonstrated for 3 days at a temperature of 25 °C.
From a microbiological point of view, unless the reconstitution method precludes the risk of microbial contamination, the medicine must be used immediately. If the product is not used immediately, the storage times and conditions during use are the responsibility of the user.
Do not store the reconstituted solution in a refrigerator (2 °C-8 °C) as this may cause precipitation.
Treosulfan has mutagenic and carcinogenic potential. Residual medicine and all materials used for reconstitution and administration must be disposed of in accordance with standard procedures applicable to antineoplastic agents, in compliance with current regulations on the disposal of hazardous waste.