Melphalan 50mg 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, pharmacist or nurse.
• If you get any side effects, talk to your doctor or pharmacist. 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

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 Mephalan
• 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 your arteries
• you are using combined oral contraception (the pill). This is because of the increased risk of venous thromboembolism (a blood clot that forms in a vein and migrates to another location) in patients with multiple myeloma.

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.

Men who are receiving melphalan should not father a child during treatment and up to 3 months afterwards.

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

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

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

• other cytotoxic medicines (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).

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 this medicine is given.

Pregnancy

Treatment with melphalan is not recommended during pregnancy because it may cause permanent damage to a foetus. 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 are having this injection. 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.

Breast-feeding

It is unknown whether melphalan is excreted in human breast milk. Do not breast-feed 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.

Women of childbearing potential should use effective contraceptive measures during treatment with melphalan and for 6 months after the end of 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 or 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 53.5 mg sodium (main component of cooking/table salt) in each vial. This is equivalent to 2.7% of the recommended maximum daily dietary intake of sodium for an adult.

This medicinal product contains 5% ethanol (alcohol) respectively 0.4 g per vial equivalent to 10 ml beer or 4 ml wine per vial.

Harmful for those suffering from alcoholism.

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

The amount of alcohol in this medicinal product may alter the effects of other medicines.

The amount of alcohol in this medicinal product may impair your ability to drive or use machines.

This medicine contains 6.2 g propylene glycol in each vial.

Propylene glycol in this medicine can have the same effects as drinking alcohol and increase the likelihood of side effects.

Do not use this medicine in children less than 5 years old.

Use this medicine only if recommended by a doctor. If you suffer from a liver or kidney disease, do not take this medicine unless recommended by your doctor. Your doctor may carry out extra checks while you are taking this medicine.

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 medicines 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)
• treatment with melphalan can cause a lowering of the white blood cell count. White blood cells fight infection, and when there are too few white blood cells, infections can occur
• 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
• if you experience any of the symptoms/signs which may be related to a blood clot (thromboembolic event) such as shortness of breath, chest pain, arm or leg swelling, especially if you are treated with melphalan in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone.

If melphalan is injected directly into your arm or leg it is possible that some of the drug can leak in to surrounding tissue and cause damage to that tissue. Symptoms of this include slight discomfort in the area, mild redness of the skin or a mild rash. In rare cases death of surrounding skin tissue, ulcers and damage to deeper tissue may occur.

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

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

• a fall in the number of blood cells and platelets
• feeling sick (nausea), being sick (vomiting) and diarrhoea, - with high doses of melphalan
• 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
• Inflammation of the soft tissue lining of the stomach (gastrointestinal mucosa).

Unommon side effects (may affect up to 1 in 100 people):

• acute kidney injury.

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 fibres (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).

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

It is also possible that the use of melphalan will increase the risk of developing another type of cancer called secondary acute leukaemia (cancer of the blood) in the future. Secondary acute leukaemia causes bone marrow (tissue in your bones that produces red and white blood cells) to produce large numbers of cells that do not work properly. Symptoms of this condition include tiredness, fever, infection and bruising. The condition may also be detected by a blood test which will show if there are large numbers of cells in your blood that are not working properly and too few blood cells that are working properly.

Tell your doctor as soon as possible if you have any of these symptoms. You may need to stop taking melphalan, but only your doctor can tell you if that is the case.

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 substance is melphalan. Each vial contains 50 mg of melphalan.

The other ingredients are:

Vial with powder: povidone K12 and hydrochloric acid, dilute.

Vial with solvent: water for injections, sodium citrate dihydrate, propylene glycol and ethanol.

Melphalan is dissolved in a diluent before being injected.

Each pack contains one melphalan vial and one solvent vial.

The powder vial contains 50 mg of the active substance melphalan in a powder format and the solvent vial contains 10 ml of a solvent in which to reconstitute (dissolve) the powder. When a vial of melphalan powder is reconstituted with 10 ml of the solvent, the resultant solution contains 5 mg/ml anhydrous melphalan.

Powder: Clear type I moulded glass vial sealed with omniflex 3G coated bromobutyl rubber stopper and flip off aluminium seal having orange colour polypropylene button with matte finish. Vials may or may not be sleeved with shrink sleeves. Pack size: 1 vial containing 50 mg melphalan.

Solvent: Clear type I moulded glass vial sealed with bromobutyl rubber stopper and flip off aluminium seal having orange colour polypropylene button with matte finish.

Pack size: 1 vial containing 10 ml.

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