Melphalan 50 mg powder and solvent for solution for injection/infusion

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• 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 are given Melphalan
3. How Melphalan will be given
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.

Before treatment with Melphalan, tell your doctor if any of the following apply to you:

• 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 being treated with Melphalan.
• you have a blood clot in your leg (thrombosis), lung (pulmonary embolism) or any other part of your body, or have ever had it
• you have a condition that gives you an increased chance of getting a blood clot in you arteries
• men who are receiving Melphalan should not father a child during treatment and up to 3 months afterwards.

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 SUN.

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

In particular, tell your doctor or nurse if you are taking any of the following

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

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before this medicine is given.

Pregnancy

Treatment with Melphalan is not recommended during pregnancy because it may cause permanent damage to a foetus. If you are already pregnant, it is important to talk to your doctor before being given Melphalan. Your doctor will consider the risks and benefits to you and your baby of treatment with Melphalan.

Reliable contraceptive precautions must be taken to avoid pregnancy whilst you or your partner are having this injection/infusion.

Breastfeeding

It is unknown whether Melphalan is excreted in human breast milk. Do not breastfeed while being given Melphalan.

Fertility

Melphalan can affect ovaries or sperm, which may cause infertility (inability to have a baby). In women, menstruation can stop (amenorrhoea) and in men, a complete lack of sperm can be observed (azoospermia) as a result of Melphalan treatment. Therefore men are advised to have a consultation on sperm preservation before treatment.

It is recommended that men who are receiving Melphalan do not father a child during treatment and up to 3 months afterwards. Talk to your doctor if you would like to use effective and reliable contraceptives.

Effects on the ability to drive and operate machinery in patients taking this medicine have not been studied. It is not expected that this medicine will affect the ability to drive or operate machines.

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.

This medicine contains 5% ethanol (alcohol), equivalent to 10 ml beer or 2.4 ml wine per dose. Harmful for those suffering from alcoholism.

To be taken into account in pregnant or breastfeeding women, children and high-risk groups such as patients with liver disease, or epilepsy.

May cause alcohol-like symptoms.

Melphalan can be given

• as an infusion (drip) into your vein
• into an artery, administered to a certain body part (perfusion).

Your doctor will decide how much Melphalan you will be given. The amount of Melphalan depends on

• your body weight or body surface area (a specific measurement taking into account your weight and your size)
• other drugs you are having
• your disease
• your age
• whether or not you have kidney problems.

When you are given Melphalan, your doctor will take regular blood tests. This is to check the number of cells in your blood. Your doctor may change your dose as a result of these tests.

Risk of blood clots (thromboembolic events)

Your doctor will decide if you should receive a preventive treatment for blood clots in the veins. This applies during the first 5 months of treatment, or if you have an increased risk for developing a blood clot in the veins.

Melphalan is only rarely used in children. Dosing guidelines for children are not available.

There are no specific dosage adjustments for the elderly.

If you have a kidney problem, your doctor will usually give you a lower dose than other adults.

Your doctor will give you Melphalan so it is unlikely that you will receive too much. If you think you have been given too much or have missed a dose, tell your doctor or nurse.

Your doctor will give you Melphalan so it is unlikely that you will miss a dose of this medicine. If you think you have missed a dose, skip that dose and you will be given next dose at the next prescribed time. Do not use a double dose to make up for a forgotten dose.

If you feel you should stop using this medicine, consult your doctor first.

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

• 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)
• if your muscles are achy, stiff or weak and your urine is darker than usual or brown or red in colour when you are given Melphalan directly into your arm or leg.

Tell your doctor immediately if you have symptoms of blood clots in the veins, especially in the legs.

Symptoms include swelling, pain and reddening of the leg. Blood clots can travel through the blood vessels to the lungs, causing pain on the chest and difficulties in breathing.

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

• fever
  
• a fall 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)
• a tingling or warm feeling where Melphalan was injected
• problems with your muscles like wasting and aching when you are given Melphalan directly into your arm or leg.

Common side effects (may affect up to 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
• a muscle problem which can cause pain, tightness, tingling, burning or numbness called compartment syndrome. This can happen when you are given Melphalan directly into your arm or leg.

Rare side effects (may affect up to 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 sperm in the semen (azoospermia)
• death of muscle tissue (muscle necrosis)
• breakdown of muscle fibers (rhabdomyolysis)
• formation of a blood clot, a so-called thrombus, in a deep vein, especially in the legs (deep venous thrombosis) and closure of a pulmonary artery (pulmonary embolism).
• secondary solid tumours.

If you get any side effects, talk to your doctor or pharmacist. 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 or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active ingredient is melphalan hydrochloride. Each vial contains melphalan hydrochloride equivalent to 50 mg melphalan.
• The other ingredients are povidone and hydrochloric acid. Melphalan is dissolved in 10 ml of solvent before being injected. The solvent contains water for injections, sodium citrate, propylene glycol and ethanol anhydrous.

Each pack Melphalan contains one vial of Melphalan powder and one vial of solvent. The powder vial contains 50 mg of the active substance mephalan in a powder format and the solvent vial contains 10 ml of solvent in which to reconstitute (dissolve) the powder. The powder is a white to off-white freeze-dried powder or cake and the solvent is a clear colourless liquid/solution. After reconstitution with 10 ml of the solvent, the resultant solution contains 5 mg/ml melphalan.

This medicinal product is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Austria: Melphalan SUN

Denmark: Melphalan SUN

Germany: Melphalan SUN

France: Melphalan SUN

Italy: Melfalan SUN

Netherlands: Melfalanhydrochloride SUN

Norway: Melphalan SUN

Sweden: Melfalan SUN

United Kingdom (Northern Ireland): Melphalan