• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Melphalan is and what it is used for
2. What you need to know before you take Melphalan
3. How to take Melphalan
4. Possible side effects
5. How to store Melphalan
6. Contents of the pack and other information

• You are allergic to melphalan or any of the other ingredients of this medicine (listed in section 6).
• You are breastfeeding.

If you are not sure, talk to your doctor or pharmacist before taking Melphalan.

Before you take Melphalan, tell your doctor or nurse if:

• you have had radiotherapy or chemotherapy, now or recently,
• you have a kidney problem,you are going to have a vaccination or were recently vaccinated. This is because some vaccines (like polio, measles, mumps and rubella) may give you an infection if you have them whilst you are taking Melphalan.
• you are using combined oral contraception (the pill). This is because of the increased risk of venous thromboembolism in patients with multiple myeloma. You should switch to ovulation inhibitory progesterone-only pills (i.e., desogestrel). The risk of venous thromboembolism continues for 4−6 weeks after discontinuing combined oral contraception.

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

Melphalan could increase the risk of developing other types of cancer (eg secondary solid tumours) in a small number of patients, particularly when used in combination with lenalidomide, thalidomide and prednisone. Your doctor should carefully evaluate the benefits and risks when you are prescribed Melphalan.

Please tell your doctor 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, you must tell your doctor if you are taking any of the following:

• vaccines which contain live organisms (see Warnings and precautions)
• nalidixic acid (an antibiotic used to treat urinary tract infections)
• ciclosporin (used to prevent rejection of organs or tissues following a transplant or to treat certain skin conditions like psoriasis and eczema or to treat rheumatoid arthritis).
• in children, busulfan (anti-cancer medicine)

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Do not take Melphalan if you are planning to have a baby. This applies to both men and women. Reliable contraceptive precautions must be taken to avoid pregnancy whilst you or your partner is taking these tablets.

If you are already pregnant, it is important to talk to your doctor before taking Melphalan.

Do not breast-feed while taking Melphalan. Ask your doctor for advice.

Fertility

Melphalan can affect ovaries or sperm, which may cause infertility (inability to have a baby). In woman, menstruation can stop (amenorrhoea) and in men, a complete lack of sperm can be observed (azoospermia). Due to the possibility of the lack of sperm as a result of Melphalan treatment it is advised for men to have a consultation on sperm preservation before treatment. It is recommended that men who are receiving treatment with Melphalan not father a child during treatment and up to 6 months afterwards.

Effects on the ability to drive and operate machinery in patients taking this medicine have not been studied.

You should receive prophylaxis of venous thromboembolism for at least the first 5 months of treatment especially if you have additional thrombotic risk factors. Your doctor will decide what measures should be taken after careful assessment of your underlying risk factors.

If you experience any thromboembolic event, tell your doctor immediately as your treatment must be discontinued and a standard anticoagulation therapy started. Your doctor will decide if you should restart melphalan in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone once the thromboembolic events have been managed. You should continue anticoagulation therapy during the course of melphalan treatment.

• The usual dose is 0.15 mg per kilogram of your body weight each day for 4 days. This is repeated every 6 weeks.

• The usual dose is 0.2 mg per kilogram of your body weight each day for 5 days. This is repeated every 4 to 8 weeks.

• The usual dose is 0.15 mg per kilogram of your body weight each day for 5 days. This is repeated every 6 weeks.

• Initially 6 to 10 mg each day for 5 to 7 days. The dose will then be reduced to 2 to 4 mg each day.

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

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

If you have any further questions on the use of this medicine, ask your doctor or nurse.

• allergic reaction, the signs may include:
  a rash, lumps or hives on the skin
  swollen face, eyelids or lips
  sudden wheeziness and tightness of the chest
  collapse (due to cardiac arrest)
• any signs of fever or infection (sore throat, sore mouth or urinary problems)
• any unexpected bruising or bleeding or feeling extremely tired, dizzy or breathless, 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) and diarrhoea
• mouth ulcers - with high doses of Melphalan
• hair loss - with high doses of Melphalan

Common (affects less than 1 in 10 people)

• hair loss - with usual doses of Melphalan
• high levels of a chemical called urea in your blood - in people with kidney problems who are being treated for myeloma

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

• an illness where you have a low number of red blood cells as they are being destroyed prematurely - this can make you feel very tired, breathless and dizzy and can give you headaches or make your skin or eyes yellow
• lung problems which may make you cough or wheeze and make it difficult to breathe
• liver problems which may show up in your blood tests or cause jaundice (yellowing of the whites of eyes and skin)
• mouth ulcers - with normal doses of Melphalan
• skin rashes or itching skin

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

• leukaemia - cancer of the blood
• in women: your periods stopping (amenorrhoea)
• in men: absence of sperms in the semen (azoospermia)
• deep vein thrombosis (formation of a blood clot called thrombus within a deep vein, predominantly in the legs) and pulmonary embolism (a blockage of the lung’s main artery or its branches by a blood clot that breaks off and travels to the lung)

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

By reporting side effects you can help provide more information on the safety of this medicine.

The active substance is melphalan. Each Melphalan tablet contains 2 mg of melphalan.

The other ingredients are microcrystalline cellulose, crospovidone, colloidal anhydrous silica, magnesium stearate, hypromellose, titanium dioxide and macrogol.

Melphalan tablets are white to off-white film-coated, round, biconvex tablets engraved with ‘GX EH3’ on one side and ‘A’ on the other. Your Melphalan tablets are in bottles of 25 and 50 tablets. Not all pack sizes may be marketed.

Marketing Authorisation holder:

Manufacturer: