Patient leaflet - Melphalan 50 mg concentrate and solvent for solution for injection/infusion
1. What Melphalan is and what it is used for
Melphalan contains a medicine called melphalan. This belongs to a group of medicines called cytotoxics (also called chemotherapy). Melphalan is used to treat cancer. It works by reducing the numbers of certain abnormal cells your body makes.
Melphalan is used for:
- Multiple myeloma – a type of cancer that develops from cells in the bone marrow called plasma cells. Plasma cells help to fight infection and disease by producing antibodies
- Advanced cancer of the ovaries
- Childhood neuroblastoma - cancer of the nervous system.
Ask your doctor if you would like more explanation about these diseases.
2. What you need to know before you are given Melphalan
Do not take Melphalan if you:
- are allergic (hypersensitive) to melphalan or any of the other ingredients of Melphalan. (See section 6: Further information)
- suffer from a severe reduction in formation of blood cells in the bone marrow (bone marrow suppression).
Do not have Melphalan if the above applies to you. If you are not sure, talk to your doctor or nurse before having Melphalan.
Take special care with Melphalan
Before you use Melphalan, tell your doctor or nurse if you have:
- had radiotherapy or chemotherapy, now or recently
- a kidney problem.
This medicine could increase the risk of developing other types of cancer (e.g. 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 this medicine.
If you are not sure if any of the above apply to you, talk to your doctor or nurse before having Melphalan.
Taking other medicines
Please 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 drugs (chemotherapy)
- 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).
Having vaccines while you are taking Melphalan
If you are going to have a vaccination speak to your doctor or nurse before you have it. 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.
Pregnancy and breast-feeding
Do not have Melphalan if you are planning to have a baby. This applies to both men and women. Melphalan may harm your sperm or eggs. Reliable contraceptive precautions must be taken to avoid pregnancy whilst you or your partner are having this injection and for at least 6 months afterwards. Ask your doctor for advice.
If you are already pregnant, it is important to talk to your doctor before having Melphalan.
Breast-feeding
Do not breast-feed while having Melphalan. Ask your doctor or midwife for advice.
Melphalan contains Sodium
This medicinal product contains 195mg sodium (main component of cooking/table salt) per vial (after first dilution, 50mg/10ml solution). This is equivalent to 9.75% of the WHO recommended maximum daily intake of 2g sodium for an adult.
Melphalan contains propylene glycol
This medicine contains 103mg propylene glycol in each 1ml concentrate vial which is equivalent to 103mg/ml.
If your baby is less than 4 weeks old, talk to your doctor or pharmacist before giving them this medicine, in particular if the baby is given other medicines that contain propylene glycol or alcohol.
If your child is less than 5 years old, talk to your doctor or pharmacist before giving them this medicine, in particular if they use other medicines that contain propylene glycol or alcohol.
If you are pregnant, do not take this medicine unless recommended by your doctor. Your doctor may carry out extra checks while you are taking this medicine.
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.
Melphalan contains Sulfobutyl-ether-β-cyclodextrin
If you have a kidney disease, talk to your doctor before you receive this medicine.
3. How to use Melphalan
Melphalan should only be prescribed for you by a specialist doctor who is experienced in treating blood problems or cancer.
Melphalan can be given:
- as an infusion into your vein.
Your doctor will decide how much Melphalan you will have. 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 taking
- 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 sometimes change your dose as a result of these tests.
If you are given more Melphalan than you should
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.
4. Possible side effects
Like all medicines, Melphalan 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:
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 have Melphalan directly into your arm or leg.
Talk to your doctor if you have any of the following side effects which may also occur with this medicine:
Very common (affects more than 1 in 10 people)
- a drop in the number of red and white 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 transient heat sensation when Melphalan is injected
- problems with your muscles like wasting and aching – when you have Melphalan directly into your arm or leg.
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
- a muscle problem which can cause pain, tightness, tingling, burning or numbness – called compartment syndrome. This can happen when you have Melphalan directly into your arm or leg.
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 (haemolytic anaemia) – 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.
The following side effects also occur with Melphalan:
- leukaemia – cancer of the blood
- myelodysplastic syndrome - cancer of immature blood cells in the bone marrow
- in women: your periods stopping.
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.
The following information is intended for healthcare professionals only:
Instructions for Use and Handling
Method of administration
For intravenous administration, it is recommended that Melphalan is injected slowly into a fast-running infusion solution via a swabbed injection port. If direct injection into a fast-running infusion is not appropriate, Melphalan solution may be administered diluted in an infusion bag.
Melphalan is not compatible with infusion solutions containing dextrose, and it is recommended that ONLY sodium chloride 9mg/ml (0.9%) solution for injection is used.
Should any visible turbidity or crystallisation appear in the diluted solutions, the preparation must be discarded.
Care should be taken to avoid possible extravasation of Melphalan and in cases of poor peripheral venous access, consideration should be given to use of a central venous line.
If high-dose Melphalan is administered with or without transplantation (autologous bone marrow, allogenic or haematopoietic stem cell), administration via a central venous line is recommended as extravasation and subsequent local tissue damage may occur if peripheral administration is used (see section 4.4).
Injection /infusion
For instructions on dilution of the medicinal product before administration, see section 6.6.
After dilution the appearance of the product should be a clear solution, see section 6.6.
Incompatibilities
Melphalan is not compatible with infusion solutions containing dextrose and it is recommended that ONLY sodium chloride 9mg/ml (0.9%) solution for injection is used.
Special precautions for storage
Store in a refrigerator (2°C - 8°C).
Keep the vials in the outer carton in order to protect from light.
After first dilution of Melphalan 50mg concentrate with 9ml of the supplied solvent Chemical and physical in-use stability has been demonstrated for 24 hours at 2 to 8°C and 1 hour at 25°C.
After further dilution of the concentrate-solvent mixture with sodium chloride 9mg/ml (0.9%) solution for injection
Chemical and physical in-use stability of the solution in polyethylene containers diluted to 0.45mg/ml has been demonstrated for 4 hours when stored at ambient temperature 25°C in addition to the 1 hour storage after first dilution at 25°C.
From a microbiological point of view, unless the method of opening and dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of user.
Safe Handling of Melphalan
Melphalan should be prepared for administration either by or under the direct supervision of a pharmacist who is familiar with its properties and safe handling requirements.
Refer to local cytotoxic guidelines before commencing.
Melphalan should be prepared for use in the aseptic unit of a pharmacy equipped with a suitable vertical laminar flow cabinet. Where such a facility is not available, a specially designated side room of a ward or clinic may be used.
Personnel preparing or handling Melphalan should wear the following protective clothing:
- Disposable gloves of surgical latex or polyvinylchloride of a suitable quality (rubber gloves are not adequate)
- Surgical facemask of suitable quality
- Protective goggles or glasses which should be washed thoroughly with water after use
- Disposable apron
- In an aseptic facility, other suitable clothing will be required.
Any spillage should be dealt with immediately (by personnel wearing suitable protective clothing), by mopping with damp, disposable paper towels which are placed in a high-risk waste disposal bag after use and disposed of in compliance with relevant local legislation. Contaminated surfaces should be washed with copious quantities of water.
Should melphalan solution come into contact with the skin, wash immediately and thoroughly with soap and plenty of cold water. In such instances it may be prudent to seek medical advice.
In case of contact with eyes, IMMEDIATE irrigation with sodium chloride eye wash should be carried out and medical attention sought without delay. If sodium chloride solution is not available, large volumes of water may be used.
Staff who are pregnant or trying to conceive should not handle Melphalan. Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist 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 Website: 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.
5. How to store Melphalan
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 vials, label and carton after “EXP”. The expiry date refers to the last day of that month.
Keep the vials in the outer carton in order to protect from light.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
Do not use this medicine if you notice visible particles in solution.
Store in a refrigerator (2°C - 8°C).
6. Contents of the pack and other information
What Melphalan contains
- The active is melphalan hydrochloride.
The other ingredients are:
Concentrate: Monothioglycerol, Propylene glycol, Sodium chloride and Macrogol 400
Solvent: Sulfobutylbetadex sodium, Sodium chloride, Sodium acetate trihydrate and Water for injections
What Melphalan looks like and contents of the pack
Each pack contains one vial of concentrate and one vial of solvent.
Concentrate
Clear glass vial (10ml) with flurotec plus rubber stopper and an aluminium flip off seal containing 1ml of concentrate. 1ml of concentrate contains melphalan hydrochloride equivalent to 50mg melphalan.
Solvent
Clear glass vial (10ml) with flurotec plus rubber stopper and an aluminium flip off seal containing 9ml of solvent.
After first dilution of the concentrate with 9ml of the supplied solvent, the concentration of melphalan is 5mg/ml.
Marketing Authorisation Holder
Accord, Barnstaple, EX32 8NS, UK
Manufacturers
Accord Healthcare Limited
Sage House, 319 Pinner Road
North Harrow, Middlesex
HA1 4HF, United Kingdom
Accord Healthcare Polska Sp.z.o.o.
Ul. Lutomierska 50,
95-200, Pabianice, Poland
Accord Healthcare B.V.
Winthontlaan 200, 3526KV Utrecht
The Netherlands
Laboratori Fundació Dau
C/ C, 12-14 Pol. Ind.
Zona Franca, Barcelona, 08040, Spain
This leaflet was last revised in March 2023
If you would like a leaflet with larger text, please contact
01271 385257
Preparation of Melphalan
(See also above, Safe Handling of Melphalan).
Note: Both the Melphalan 50mg concentrate and solvent vials contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the entire contents of the accompanying solvent, there is solution containing 5mg/ml melphalan.
Melphalan should be prepared by first dilution with the solvent provided and second dilution with sodium chloride 9mg/ml (0.9%) solution for injection. After first dilution of the concentrate with 9ml of the solvent, the concentration of melphalan is 5mg/ml. The preferred method of administration is injection of 5mg/ml concentration solution into fast running infusion solution. If direct injection into a fast running infusion is not appropriate, Melphalan solution may be administered diluted in an infusion bag to obtain a final concentration between 0.45 and 4.0mg/ml.
STEP 1: DILUTION OF THE CONCENTRATE VIAL WITH THE SUPPLIED SOLVENT
- Aseptically withdraw the entire contents of the supplied solvent
- Inject the entire contents of the solvent into the vial of Melphalan 50mg concentrate.
- Mix the solvent and the concentrate well by inversion of the vial. It should also be noted that the mixing process may create a considerable amount of very small air bubbles. These bubbles may persist and may take a further 2 to 3 minutes to clear.
- The resulting 10ml solution contains the equivalent of 5mg/ml anhydrous melphalan and has a pH of approximately 4.5.
The solution should be a clear colourless to pale yellow solution, free from visible particulate matter. If such a solution is not obtained it should be discarded. (See Disposal, above).
STEP 2: DILUTION OF CONCENTRATE–SOLVENT MIXTURE IN SODIUM CHLORIDE 9MG/ML (0.9%) SOLUTION FOR INJECTION
- Aseptically withdraw the required amount of concentrate-solvent mixture (containing melphalan 5mg/ml) from the vial.
- Inject the withdrawn volume into appropriate volume of sodium chloride 9mg/ml (0.9%) solution for injection and mix by inversion of the bag or bottle.
- The solution should be a clear colourless to pale yellow solution, free from visible particulate matter.
The final diluted solution in the bag or bottle should be inspected visually for particulate matter prior to administration.
Melphalan is not compatible with infusion solutions containing dextrose and it is recommended that ONLY sodium chloride 9mg/ml (0.9%) solution for injection is used.
Should any visible turbidity or crystallisation appear in the diluted solutions, the preparation must be discarded.
The vials are for single use only.
Disposal
Melphalan should be disposed of in compliance with relevant local legislation. In the absence of such guidelines, the solution should be disposed of in a manner appropriate for toxic chemicals, for example, high-temperature incineration or deep burial.
Disposal of sharp objects, such as needles, syringes, administration sets and ampoules should be in rigid containers labelled with a suitable hazard warning seal. Personnel involved in disposal should be aware of the precautions to be observed, and the material should be destroyed by incineration if appropriate. All disposal must be in accordance with local regulatory requirements.
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