Myleran

Package leaflet: Information for the patient

Myleran, 2 mg, film-coated tablets
Busulfanum
Read the entire leaflet carefully before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are similar.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Myleran is and what it is 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 Myleran is and what it is 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 treatment prior to bone marrow or haematopoietic (stem) cell transplantation, and also in the treatment of certain blood disorders, including specific cancers. 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 in your particular condition.
Myleran is used in the following conditions:

• Chronic myeloid leukaemia – a type of cancer affecting certain blood-forming cells in the bone marrow (the site where blood cells are produced), leading to an increased number of white blood cells in the blood. This may cause infections and bleeding.
• Polycythaemia vera – a disorder causing an increased number of red blood cells in the blood. This makes the blood thicker and may lead to blood clots. This can cause symptoms such as headache, dizziness, and shortness of breath, etc.
• Thrombocythaemia – a disorder affecting platelets (blood cells that help blood to clot), or in which platelets do not function properly, leading to bleeding symptoms such as nosebleeds, bleeding gums, and easy bruising.
• Myelofibrosis – a disorder in which the bone marrow is replaced by fibrous (scar-like) tissue. This leads to abnormal production of white and red blood cells. This may cause symptoms such as fatigue, abdominal swelling, bleeding, and bruising.
• Preparative treatment prior to haematopoietic cell transplantation. In this case, blood cells from the bone marrow of a healthy donor are transferred into the patient's bone marrow to help produce healthy blood cells. Please ask your doctor if you need more information about these conditions.

2. Important information before using Myleran

When not to use Myleran:

• if the patient is allergic to busulfan or to any of the other ingredients of this medicine (listed in section 6),
• if the patient has previously taken Myleran and the medicine did not work. In case of doubt, consult a doctor before using Myleran.

Warnings and precautions
Myleran is a potent cytotoxic medicine that causes a significant reduction in blood cell counts.
This is the intended effect of the medicine when taken at the recommended dose. Therefore, close monitoring will be carried out.
Taking Myleran may increase the risk of developing another malignant tumour (a type of cancer) in the future.
Before starting treatment with Myleran, discuss with your doctor if:

• the patient is currently or has recently undergone radiotherapy or any other chemotherapy, apart from the one discussed here, or has ever received a stem cell transplant. This is because patients receiving Myleran may develop a serious liver condition (called hepatic veno-occlusive disease). The risk of developing hepatic veno-occlusive disease is increased in patients who have undergone radiotherapy, received more than three cycles of chemotherapy, or received a stem cell transplant,
• the patient has been diagnosed with high levels of uric acid or gout, which may cause joint pain;
• the patient has liver, kidney or lung disorders.

Myleran may cause infertility in both men and women. Before starting treatment with this medicine, men should discuss with their doctor the possibility of sperm banking at a facility offering such services.
If the patient is unsure whether any of the above situations apply, medical advice should be sought from a doctor or pharmacist before using Myleran.
Myleran and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take. Myleran may interact with other medicines and caution should be exercised when using it.

• Other cytotoxic medicines (chemotherapy) – if used together with Myleran, there is an increased risk of adverse effects affecting the lungs.
• Phenytoin (used to treat seizures and prevent seizures) – the doctor may wish to switch from phenytoin to another medicine.
• Vaccines containing live organisms (such as oral polio vaccine, measles, mumps and rubella vaccine) – Myleran may cause the body to become less able to fight infections.
• Itraconazole (used for fungal infections) or metronidazole (used for bacterial infections) – may cause severe adverse reactions when used together with Myleran.
• Cyclophosphamide (used in certain blood disorders) – if used together with Myleran, it is best if the first dose of cyclophosphamide is administered 24 hours or more after the last dose of Myleran. This reduces the risk of potential adverse effects.
• If anaesthesia is required during surgery in hospital or at the dentist. In such a case, inform the doctor or dentist that the patient is taking Myleran.
• Caution is advised when using paracetamol during treatment with Myleran.
• Deferasirox (a medicine used to remove excess iron from the body).

Myleran with food and drink
Not applicable.
Pregnancy, breastfeeding and fertility
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 Myleran.
Breastfeeding must not be undertaken during treatment with Myleran.
Myleran may damage sperm or egg cells. Effective contraception should be used to avoid pregnancy while either partner is taking this medicine.
Driving and using machines
There is no data available on the effects of busulfan on the ability to drive and operate machinery.
Myleran contains lactose
If the patient has previously been diagnosed with an intolerance to certain sugars, the patient should consult their doctor before taking this medicine.

3. How to use Myleran

This medicine should always be taken exactly as prescribed by the doctor. In case of doubt, consult
your doctor.
Myleran should only be administered by a physician experienced in the treatment of blood disorders.
Your doctor will inform you of the dose and how often you should take this medicine.
Tablets must not be broken, crushed, or chewed.
The dose of Myleran used depends on the specific blood disorder or blood cancer (see
section 1).

• Your doctor may also adjust the dosage during treatment, depending on your needs.
• The dose may sometimes be adjusted if the patient is overweight.
• If a patient is taking high doses of Myleran, the doctor may also prescribe another medicine called a benzodiazepine. This helps prevent seizures.
• During Myleran therapy, your doctor may perform regular blood tests to monitor blood cell counts; based on the results of these tests, the dose of the medicine may be adjusted.

Haematopoietic stem cell transplantation

• Myleran is usually given every 6 hours for 4 days, starting on day 7 before transplantation.
• Two days before transplantation, the patient may also receive another cytotoxic medicine called cyclophosphamide. Cyclophosphamide must not be administered until at least 24 hours have passed since 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 according to body surface area. Myleran is taken every 6 hours for 4 days.

Chronic myeloid leukaemia
Adults

• The initial dose is usually up to 4 mg and may be given as a single dose. The doctor will then determine the subsequent doses based on the patient's body weight.
• A treatment course usually lasts 12 to 20 weeks. The patient may receive more than one treatment cycle.
• Some patients need to take Myleran for a longer period. If long-term treatment is required, the usual dose is 0.5 mg to 2 mg per day. If the prescribed dose is less than 2 mg per day, the doctor may recommend taking tablets only on certain days. It is essential to strictly follow the doctor’s instructions.

Children

• Chronic myeloid leukaemia is rare in children, and therefore there are no established dosage recommendations for Myleran in this population.

Polycythaemia vera

• The usual dose is 4 to 6 mg daily.
• A treatment cycle usually lasts 4 to 6 weeks. The doctor may repeat this cycle if necessary. Some patients need to take Myleran for a prolonged period. If long-term treatment is required, the usual dose is 2 to 3 mg daily.

Myelofibrosis and essential thrombocythaemia

• The usual dose is 2 to 4 mg daily.

If you take more Myleran than you should
Contact your doctor immediately or go to the hospital without delay. Take the medicine packaging
with you, even if it no longer contains tablets.
If you forget to take Myleran
Inform your doctor. Do not take a double dose to make up for a missed dose.
Stopping Myleran
Do not stop taking Myleran without consulting your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences them.
If the patient experiences any of the following symptoms, a specialist doctor should be informed immediately
or the patient should go immediately to the nearest hospital:

• any symptoms of high fever or infection (sore throat, inflammation of the oral mucosa or urinary disorders). Treatment with Myleran may
  cause a reduction in the number of white blood cells. White blood cells fight infections; when their number is low, infections may occur;
• sudden appearance of bruises or bleeding, as this may indicate that too few blood cells of a certain type are being produced;
• if the patient feels suddenly unwell (even if body temperature is normal).

Very common (affects more than 1 in 10 people)

• reduction in the number of blood cells and platelets,
• nausea, vomiting, diarrhoea and oral ulceration – when high doses of Myleran are used,
• yellowing of the whites of the eyes or skin (jaundice), liver damage and damage to the bile ducts – when high doses of Myleran are used,
• in women, menstrual periods may cease, fertility may be impaired and menopause may start earlier – when high doses of Myleran are used,
• in girls, sexual maturation may be delayed or may not occur at all,
• in boys and men, sperm production may be delayed, reduced or suppressed, and testicle size may decrease,
• lung inflammation without signs of infection – called idiopathic pneumonitis – when high doses of Myleran are used.

Common (affects up to 1 in 10 people)

• irregular heartbeat – especially if the patient suffers from an inherited blood disorder called thalassaemia when high doses of Myleran are used,
• lung inflammation causing breathlessness, cough and fever – called interstitial pneumonitis,
• hair loss – when high doses of Myleran are used,
• appearance of dark spots on the skin,
• blood in the urine and pain during urination (cystitis) – when high doses of Myleran and a medicine called cyclophosphamide are used simultaneously,
• leukaemia.

Uncommon (affects up to 1 in 100 people)

• in women, menstrual periods may cease, fertility may be impaired and menopause may start earlier – when normal doses of Myleran are used.

Rare (affects up to 1 in 1000 people)

• significant reduction in the number of red blood cells, which may cause fatigue, weakness, bruising and increased susceptibility to infections – called aplastic anaemia,
• seizures or epileptic fits – when high doses of Myleran are used,
• cataract or other eye disorders – after bone marrow transplantation and when high doses of Myleran are used,
• nausea and vomiting, diarrhoea and oral ulceration when normal doses of Myleran are used. These symptoms can be alleviated by dividing the daily dose into smaller doses administered throughout the day.
• jaundice (yellowing of the whites of the eyes or skin) and damage to the bile ducts – when high doses of Myleran are used,
• hair loss – when normal doses of Myleran are used,
• 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 and difficulty speaking and moving arms and legs – a disease called myasthenia,
• breast enlargement in men,
• weakness, feeling of severe fatigue, weight loss, nausea, vomiting and dark spots on the skin – these symptoms resemble Addison's disease (although adrenal gland function remains normal).

Frequency not known (cannot be estimated from available data)

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

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed
in this leaflet, the patient should inform their doctor, pharmacist or nurse. Adverse reactions
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, 02-222 Warsaw
tel.: + 48 22 49 21 301
fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Myleran

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the box after: "Expiry date (EXP)" and on the bottle after: "EXP". The expiry date refers to the last day of the month indicated.
Store at a temperature not exceeding 25°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Proper disposal helps 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, pregelatinized starch, and magnesium stearate.
  Coating composition: 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, printed with "GX EF3" on one side and "M" on the other.
It is supplied in an amber glass bottle contained in a cardboard box.
Pack sizes: 25 or 100 coated tablets.

Marketing Authorisation 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