1. What Myleran is and what it is used for

Myleran tablets contain a medicine called Busulphan. This belongs to a group of medicines called cytotoxics (also called chemotherapy). Myleran is used for certain blood problems and cancers of the blood. It works by reducing the number of new blood cells your body makes.

Myleran is used for:

• Chronic myeloid leukaemia - a disease that increases the number of white blood cells. This can cause infections and bleeding.
•  Polycythaemia vera a disease which increases the number of red cells in your blood. This makes the blood thicken and causes blood clots. This leads to headaches, dizziness and shortness of breath.
• Thrombocythaemia a disease which affects platelets (blood cells which help blood to clot). There may be an increase in platelets – which causes blood clots. Or the platelets do not work properly - which causes bleeding such as nose bleeds, bleeding gums and bruising easily.
• Myelofibrosis a disease where bone marrow (where blood cells are made) is replaced by scar (fibrous) tissue. This causes red and white blood cells to be made wrongly. This can cause tiredness, bloated stomach, bleeding, and bruising.
• Preparing you before haemopoietic progenitor cell transplantation. This is where blood cells growing in a healthy donor’s bone marrow are transferred to your bone marrow to help you produce healthy cells.

Ask your doctor if you would like more explanation about these diseases.

2. What you need to know before you take Myleran

Do not take Myleran if:

•  You are allergic (hypersensitive) to Myleran or any of the other ingredients of this medicine (listed in section 6).
•  You have taken Myleran before and it did not work.

Do not take Myleran if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before taking Myleran.

Take special care with Myleran

Talk to your doctor or pharmacist before taking Myleran, if:

• You have had radiotherapy, now or recently.
• You have an inherited blood problem called thalassaemia.
• You have ever had gout (painful and swollen joints caused by uric acid crystals). You may need treatment for your gout before you start taking Myleran.
• You have a liver, kidney or lung problem.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before taking Myleran.

Other medicines and Myleran

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

This includes herbal medicines.

In particular tell your doctor or pharmacist if you are taking any of the following:

• Other cytotoxic drugs (chemotherapy) – when used with Myleran there is a greater chance of side effects, such as breathing problems.
• Phenytoin (used to treat and prevent fits) – your doctor may need to change your phenytoin to a different medicine.
•  Vaccines which contain live organisms (such as oral polio, measles, mumps and rubella) – Myleran can make your body less able to fight infections.
•  Itraconazole (for fungal infections) or metronidazole (for bacterial infections) - they can cause serious side effects if used with Myleran.
• Cyclophosphamide (used for certain types of blood disorders) - if used with Myleran, it is best that your first cyclophosphamide dose is given 24 hours or longer after the last Myleran dose. This will reduce the chance of any possible side effects.
•  An anaesthetic for an operation at the hospital or dentist. If so, tell your doctor or dentist that you are taking Myleran.
• The use of Paracetamol during Myleran administration should be used with caution.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. This applies to both men and women.

Myleran may harm your sperm or eggs. Reliable contraceptive precautions must be taken to avoid pregnancy whilst you or your partner are taking these tablets. Ask your doctor for advice.

If you are already pregnant, it is important to talk to your doctor before taking Myleran. Do not breastfeed while taking Myleran. Ask your doctor or midwife for advice.

Myleran contains lactose

If you have been told by your doctor that you have intolerance to some sugars contact your doctor before taking this medicinal product.

3. How to take Myleran

Myleran should only be given to you by a specialist doctor who is experienced in treating blood problems.

Always take Myleran exactly as your doctor has told you. It is important to take your medicine at the right times. The label on your pack will tell you how many tablets to take and how often to take them. If the label doesn’t say or if you are not sure, ask your doctor, nurse or pharmacist.

• Myleran treatment must be initiated and monitored under the supervision of a physician experienced in the antineoplastic agents.
•  Myleran is a cytotoxic drug. Need caution when handling Myleran to minimize risk of exposure.
•  Tablets should be swallowed whole.
•  The tablets should not be broken or crushed or chewed.

The dose of Myleran depends on your blood problem or blood cancer (see section 1).

•   Your doctor may also change your dose during your treatment, depending on your needs.
• The dose can sometimes be changed if you are over-weight.
•  If you take a high-dose of Myleran, your doctor may also prescribe another medicine called a benzodiazepine. This will help to stop you having a fit.
• When you take Myleran your doctor will take regular blood tests. This is to check the number of cells in your blood. Your doctor may sometimes change your dose as a result.

Chronic myeloid leukaemia The usual first dose is up to 4 mg, given as a single dose. Your doctor will then decide on the size of the next doses, based on your weight.

•  The treatment is normally a course which lasts for 12 to 20 weeks. You may have more than one course of treatment.
• Some people have to take Myleran long term. If you have to take it long term, the usual dose is 0.5 mg to 2 mg each day. If your dose is less than 2 mg each day, your doctor might ask you to take tablets only on certain days. Follow your doctor’s instructions carefully.
• Chronic myeloid leukaemia is rare in children and there is no recommended dose of Myleran.

Polycythaemia vera

• The usual dose is 4 to 6 mg each day.
•  The course is usually 4 to 6 weeks. This course can be repeated.
• Some people have to take Myleran long term. If you have to take it long term, the usual dose is 2 to 3 mg each day. Follow your doctor’s instructions carefully.

Myelofibrosis and essential thrombocythaemia

• The usual dose is 2 to 4 mg each day.

Haemopoietic progenitor cell transplantation

• The medicine is usually taken on days 7, 6, 5, 4 and 3 before your transplant day (Imagine your transplant day is day 0, and that you count down the days before).
•  Two days before your transplant, you will also get a medicine called cyclophosphamide. The cyclophosphamide should not be given until 24 hours have passed since your last dose of Myleran.

- Adults – The usual dose is 1 mg per kilogram of your body weight. This is taken every 6 hours.

- Children – The dose is worked out according to the surface area of your body. This is taken every 6 hours.

If you take more Myleran than you should

If you take more Myleran than you should, tell your doctor immediately or go to a hospital straight away. Take the medicine pack with you.

If you forget to take Myleran

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

4. Possible side effects

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

If you get any of the following, talk to your specialist doctor or go to hospital straight away:

• any signs of fever or infection (sore throat, sore mouth or urinary problems)
•  any unexpected bruising or bleeding, as this could mean that too few blood cells of a particular type are being produced
•  if you suddenly feel unwell (even with a normal temperature)

Talk to your doctor if you have any of the following side effects which may also happen with this medicine:

Very common (affects more than 1 in 10 people)

•   a drop in the number of blood cells and platelets
•   feeling sick (nausea), being sick (vomiting), diarrhoea and mouth ulcers - with high doses of Myleran
•   yellowing of the whites of the eyes or skin (jaundice) and liver damage - with high doses of Myleran
•    in women, periods may stop, fertility may be affected and the menopause may start early – with high doses of Myleran
•   in girls, the start of puberty may be delayed or prevented
•   in boys and men, sperm production may be delayed, reduced or stopped and your testicles may reduce in size
• inflammation of the lung with no sign of infection - called pneumonia syndrome - with high doses of Myleran

Common (affects less than 1 in 10 people)

• your heart may not be able to beat properly - especially if you have an inherited blood problem called thalassaemia
•  inflammation of the lungs which causes breathlessness, cough and raised temperature – called pneumonitis
•   hair loss (with high doses of Myleran)
• appearance of patches of dark skin
•  signs of blood in your urine and pain when passing water (bladder inflammation) - with high doses of Myleran at the same time as taking a medicine called cyclophosphamide
• leukaemia

Uncommon (affects less than 1 in 100 people)

• in women, periods may stop and fertility may be affected and menopause may start early – with usual doses of Myleran

Rare (affects less than 1 in 1,000 people)

•   a severe drop in red blood cells which can cause tiredness, weakness, bruising and make you more likely to get infections – called aplastic anaemia
•   fits or seizures - with high doses of Myleran
•  cataracts or other eye problems - after bone marrow transplantation and with high doses of Myleran
•   feeling or being sick (nausea or vomiting), diarrhoea and mouth ulcers - with usual doses of Myleran. This can be improved by splitting the dose through the day
•  jaundice (yellowing of the whites of eyes or skin) and liver damage - with usual doses of Myleran
•   hair loss (with normal doses of Myleran)
• dry mouth and lips or other skin changes including very dry skin, itching or rash

Very rare (affects less than 1 in 10,000 people)

• muscle weakness commonly leading to drooping eye lids and difficulty in speaking or using your arms and legs – called Myasthenia gravis
• enlargement of breasts in men
• weakness, feeling very tired, weight loss, feeling sick, being sick and dark skin patches – which resembles Addison’s disease (but with the adrenal glands working correctly)

Not known (frequency cannot be estimated from the available data)

•  Incomplete development of teeth

Additional side effects reported with intravenous Myleran

Very common (affects more than 1 in 10 people)

•   allergic reaction
• decrease in magnesium, calcium, potassium, phosphate and increase in blood sugar
• headache, dizziness, sleeplessness, anxiety and depression
•  increase in heart rate
•  increase or decrease of blood pressure, dilation of the blood vessels and blood clots
•  abnormal pain, heart burn, fluid in the abdomen, constipation, anal discomfort
• enlarged liver
•    back, muscle or joint pain
•  discomfort in urination, decrease in urine output, increased creatinine in blood
• fever, chills, pain, oedema (swelling from fluid accumulation in body tissues), chest pain
•  abnormal breath sounds, weight increased

Common (affects less than 1 in 10 people)

•  low blood sodium
•  confusion
•  abnormal heart rhythm, enlarged heart, inflammation of the tissue enclosing the heart, decrease heart output
•   increase in breath rate, respiratory failure, asthma, collapse of small portions of the lung, fluid around lung
•   vomiting blood, decreased movements of the gut, inflammation of the mucosa of oesophagus
• moderate kidney insufficiency, bloody urine, increase in the amount of nitrogen in the blood

Uncommon (affects less than 1 in 100 people)

• cerebral haemorrhage, abnormal brain function
• extra heart beats, decrease in heart rate, clotting of femoral artery, diffuse leak of fluid from the capillaries (small blood vessel)
•  bleeding of the stomach and/or the gut

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 which is stated on the pack after ‘Exp’. The expiry date refers to the last day of that month.
• Do not store above 25°C.
• Myleran is a cytotoxic, need caution when handling to minimize risk of exposure.
• The tablets should not be divided, broken or crushed.
• Transport and store medicine in the original container or blister.
•   For medication administration, use gloves and wash hands thoroughly before and after. If gloves are not worn, tip tablets and from their container/blister pack directly into a disposable medicine cup.
•  People who are not taking Myleran should not be exposed to it.
•  Caution should be observed in handling broken or crushed tablets Avoid direct contact of the Myleran with skin or mucous membranes. If such contact occurs, wash thoroughly with soap and water, rinse eyes thoroughly with sterile water, or plain water if sterile water is unavailable.
•   Pregnant should avoid exposure to crushed or broken coated tablets.
• Family members use gloves when handling laundry or cleaning within or around toilets.
•   Close the lid before flushing the toilet and flush twice after each use by patient, for 48 hours after receiving chemotherapy. If available, use separate bathroom from family members.
•  Conduct double washing of linens and wash them separately from other family laundry.
•  If your doctor tells you to stop taking the medication, or if it expired.  Do not throw away via wastewater or household waste. Ask your pharmacist how to throw away medicine you no longer use, or return it to your pharmacist, who will destroy them according to disposal of dangerous substance guidelines.
• These measures will help protect environment.
•   Only keep the medicine if your doctor tells you to.