Mileran

Package Leaflet: Information for the Patient

Myleran, 2 mg, Coated Tablets

Busulfan

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of Contents of the Leaflet

• 1. What is Myleran and what is it used for
• 2. Important information before taking Myleran
• 3. How to take Myleran
• 4. Possible side effects
• 5. How to store Myleran
• 6. Contents of the pack and other information

1. What is Myleran and what is it used for

Myleran tablets contain the active substance busulfan, which belongs to a group of medicines called alkylating agents (a type of cytotoxic medicine or chemotherapy). This medicine is used as a treatment before a bone marrow or stem cell transplant, and also to treat certain blood disorders, including specific types of cancer. The medicine works by reducing the number of new blood cells produced by the bone marrow. Myleran may be used in combination with other cytotoxic medicines, such as cyclophosphamide. Your doctor can explain how Myleran helps with your specific condition. Myleran is used in the following situations:

• Chronic myeloid leukemia- a type of cancer that affects certain blood cells in the bone marrow (where blood cells are produced), causing an increase in the number of white blood cells in the blood. This can lead to infections and bleeding.
• Polycythemia vera- a disease that causes an increase in the number of red blood cells in the blood. This can cause the blood to thicken and form blood clots, leading to symptoms such as headaches, dizziness, and shortness of breath.
• Essential thrombocytosis- a disease that affects platelets (blood cells that help the blood to clot) or causes platelets to not function properly, leading to symptoms related to bleeding, such as nosebleeds, bleeding gums, and easy bruising.
• Myelofibrosis- a disease in which the bone marrow is replaced by fibrous (scar) tissue, leading to abnormal production of white and red blood cells. This can cause symptoms such as fatigue, abdominal swelling, bleeding, and bruising.
• Stem cell transplantation preparation. In this case, blood cells from a healthy donor's bone marrow are transferred to the patient's bone marrow to help produce healthy cells. If you need more information about these diseases, ask your doctor.

2. Important information before taking Myleran

When not to take Myleran:

• if you are allergic to busulfan or any of the other ingredients of this medicine (listed in section 6),
• if you have taken Myleran in the past and it did not work. If in doubt, consult your doctor before taking Myleran.

Warnings and precautions

Myleran is a powerful cytotoxic medicine that can cause a significant reduction in blood cells. This is a desired effect of the medicine when taken at the recommended dose. Therefore, close monitoring will be performed. Taking Myleran may increase the risk of developing another type of cancer in the future. Before starting treatment with Myleran, discuss with your doctor if:

• you are currently or have recently undergone radiation therapy or any other chemotherapy, except for the chemotherapy mentioned in this leaflet, or if you have ever received a stem cell transplant. This is because patients taking Myleran may develop a serious liver disease (called veno-occlusive disease of the liver). The risk of developing veno-occlusive disease of the liver is increased in patients who have undergone radiation therapy, received more than three cycles of chemotherapy, or received a stem cell transplant.
• you have an excessive amount of uric acid or gout, which can cause joint pain;
• you have liver, kidney, or lung disorders.

Myleran can cause infertility in both men and women. Before starting treatment with Myleran, men should discuss with their doctor the possibility of depositing sperm in a facility that offers this service. If you are not sure if any of these situations apply to you, consult your doctor or pharmacist before taking Myleran.

Myleran and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take. Myleran may interact with other medicines, and caution should be exercised when taking it.

• Other cytotoxic medicines (chemotherapy) - if taken with Myleran, there is a greater possibility of side effects related to the lungs.
• Phenytoin (used to treat seizures and prevent seizures) - your doctor may want to switch to a different medicine.
• Vaccines containing live organisms (such as oral polio vaccine, measles, mumps, and rubella) - Myleran may cause the body to become less able to fight infections.
• Itraconazole (used to treat fungal infections) or metronidazole (used to treat bacterial infections) - may cause severe side effects if taken with Myleran.
• Cyclophosphamide (used to treat certain blood disorders) - if taken with Myleran, it is best if the first dose of cyclophosphamide is given 24 hours after the last dose of Myleran or later. This reduces the possibility of side effects.
• If you need anesthesia during surgery in a hospital or at the dentist. In this case, tell your doctor or dentist that you are taking Myleran.
• Caution should be exercised when taking paracetamol while taking Myleran.
• Deferasirox (a medicine used to remove excess iron from the body).

Taking Myleran with food and drink

Not applicable.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before taking Myleran. Do not breastfeed while taking Myleran. Myleran may damage sperm or eggs. Use effective contraception to avoid pregnancy when taking Myleran.

Driving and using machines

There is no data on the effect of busulfan on the ability to drive and use machines.

Myleran contains lactose

If you have been diagnosed with an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Myleran

Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor. Myleran should only be used by a doctor experienced in treating blood disorders. Your doctor will tell you what dose and how often to take this medicine.

Do not break, crush, or chew the tablets.

The dose of Myleran depends on the specific blood disorder or blood cancer (see section 1).

• Your doctor may also change the dose during treatment, depending on your needs.
• The dose may be changed if you are overweight.
• If you are taking high doses of Myleran, your doctor may also prescribe another medicine called a benzodiazepine to help prevent seizures.
• During treatment with Myleran, your doctor may regularly perform blood tests to check the number of blood cells in your blood; based on the results of these tests, the dose of Myleran may be changed.

Stem cell transplantation

• Myleran is usually given every 6 hours for 4 days, starting 7 days before the transplant.
• Two days before the transplant, you may also receive another cytotoxic medicine called cyclophosphamide. Cyclophosphamide should not be given until 24 hours after the last dose of Myleran.
• Adults- the usual dose is 1 mg per kilogram of body weight. Myleran is taken every 6 hours for 4 days.
• Children- the dose is determined based on body surface area. Myleran is taken every 6 hours for 4 days.

Chronic myeloid leukemia

Adults

• Usually, the first dose is up to 4 mg and may be given as a single dose. Your doctor will then decide on the size of subsequent doses based on your body weight.
• Usually, a treatment course lasting 12 to 20 weeks is used. You may receive more than one treatment cycle.
• Some patients may need to take Myleran for a longer period. If you need to take Myleran for a longer period, usually a dose of 0.5 mg to 2 mg per day is used. If the dose is less than 2 mg per day, your doctor may recommend taking the tablets only on certain days. Follow your doctor's instructions carefully.

Children

• Chronic myeloid leukemia is rare in children, and therefore, there are no dosage recommendations for Myleran.

Polycythemia vera

• Usually, the dose is 4 to 6 mg per day.
• The treatment course usually lasts 4 to 6 weeks. This course may be repeated by your doctor if necessary. Some people may need to take Myleran for a longer period. If you need to take Myleran for a longer period, usually a dose of 2 to 3 mg per day is used.

Myelofibrosis and essential thrombocytosis

• Usually, the dose is 2 to 4 mg per day.

Taking more than the recommended dose of Myleran

Inform your doctor or go to the hospital immediately. Take the medicine package with you, even if it is empty.

Missing a dose of Myleran

Tell your doctor. Do not take a double dose to make up for a missed dose.

Stopping treatment with Myleran

Do not stop taking Myleran without your doctor's advice. If you have any further questions about taking this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

If you experience any of the following symptoms, tell your doctor or go to the hospital immediately:

• any symptoms of high fever or infection (sore throat, mouth ulcers, or urinary disorders). Treatment with Myleran can cause a reduction in the number of white blood cells. White blood cells fight infections; when there are not enough white blood cells, infections can occur;

Myleran can cause a reduction in the number of blood cells, which can lead to:

• unexpectedbruising or bleeding, which may indicate that there are not enough blood cells of a certain type;
• if you suddenlyfeel unwell (even if your body temperature is normal).

Very common (affects more than 1 in 10 people)

• reduction in the number of blood cells and platelets,
• nausea (feeling sick), vomiting, diarrhea, and mouth ulcers - during treatment with high doses of Myleran,
• yellowing of the whites of the eyes or skin (jaundice), liver damage, and bile duct damage - during treatment with high doses of Myleran,
• in women, menstrual cessation, fertility disorders, and early menopause - during treatment with high doses of Myleran,
• in girls, delayed or absent puberty,
• in boys and men, delayed, reduced, or inhibited sperm production, and reduced testicle size,
• pneumonia without signs of infection - called idiopathic pneumonia - during treatment with high doses of Myleran.

Common (affects up to 1 in 10 people)

• abnormal heart rhythm - especially if you have a congenital blood disorder called thalassemia during treatment with high doses of Myleran,
• pneumonia that causes shortness of breath, cough, and fever - called interstitial pneumonia,
• hair loss - during treatment with high doses of Myleran,
• appearance of dark spots on the skin,
• blood in the urine and pain when urinating (urinary tract infection) - during treatment with high doses of Myleran and cyclophosphamide,
• leukemia.

Uncommon (affects up to 1 in 100 people)

• in women, menstrual cessation, fertility disorders, and early menopause - during treatment with standard doses of Myleran.

Rare (affects up to 1 in 1,000 people)

• severe reduction in the number of red blood cells, which can cause fatigue, weakness, bruising, and increased risk of infection - called aplastic anemia,
• seizures or convulsions - during treatment with high doses of Myleran,
• cataracts or other eye disorders - after bone marrow transplantation and during treatment with high doses of Myleran,
• nausea (feeling sick) and vomiting, diarrhea, and mouth ulcers during treatment with standard doses of Myleran. These symptoms can be alleviated by dividing the daily dose of Myleran into smaller doses taken throughout the day.
• jaundice (yellowing of the whites of the eyes or skin) and bile duct damage - during treatment with high doses of Myleran,
• hair loss - during treatment with standard doses of Myleran,
• abnormal development of certain types of cells,
• dry mouth, dry lips, and other skin changes, such as excessive dryness of the skin, itching, or rash.

Very rare (affects up to 1 in 10,000 people)

• muscle weakness, often causing drooping eyelids, difficulty speaking, and difficulty moving arms and legs - a disease called myasthenia,
• breast enlargement in men,
• weakness, feeling extremely tired, weight loss, nausea, vomiting, and dark spots on the skin - symptoms that resemble Addison's disease (although adrenal function remains normal).

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

• incomplete development of teeth,
• increased blood pressure in the blood vessels of the lungs (pulmonary hypertension).

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Medicinal Product Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 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 authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Myleran

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date stated on the carton after "EXP" and on the bottle after "EXP". The expiry date refers to the last day of the month. Store in a temperature not exceeding 25°C. 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. Contents of the pack and other information

What Myleran contains

• The active substance is busulfan. Each coated tablet contains 2 mg of busulfan.
• The other ingredients are lactose, starch, magnesium stearate. The coating contains Opadry White OY-S-7322 [hypromellose, titanium dioxide (E 171), triacetin].

What Myleran looks like and contents of the pack

Myleran is a round, biconvex, white, coated tablet with "GX EF3" engraved on one side and "M" on the other. It is available in a glass bottle in a cardboard box. The pack size is 25 or 100 coated tablets.

Marketing authorization holder

Aspen Pharma Trading Limited, 3016 Lake Drive, Citywest Business Campus, Dublin 24, Ireland, tel: +48 22 104 21 00

Manufacturer

EXCELLA GmbH & Co. KG, Nürnberger Strasse 12, 90537 Feucht, Germany

Date of last revision of the leaflet: 05/2025