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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Melphalan Aspen 50 mg powder and solvent for injectable solution and for perfusion

melphalan

Read the entire package leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• This medicine has been prescribed for you only, and you must not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the package leaflet

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

1. What Melfalán Aspen is and what it is used for

Melfalán Aspen contains the active substance melfalan, which belongs to a group of medicines known as cytotoxic agents (also referred to as chemotherapy). It is used to treat certain types of cancer. It works by reducing the number of abnormal cells that your body produces.

Melfalán Aspen is used for:

• Multiple myeloma: a type of cancer that arises in plasma cells in the bone marrow. Plasma cells help fight infections and diseases by producing antibodies.
• Advanced ovarian cancer.
• Advanced neuroblastoma (a type of cancer affecting the nervous system) in children.
• Malignant melanoma: a type of skin cancer.
• Soft tissue sarcoma: cancer of muscle, fat, fibrous tissue, blood vessels, or other supportive tissues of the body.

Ask your doctor if you would like further information about these conditions.

Consult a doctor if your condition worsens or does not improve.

2. What you need to know before using Melfalán Aspen

Do not use Melfalán Aspen:

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

If you are unsure, consult your doctor or nurse before starting treatment with Melfalán Aspen.

Warnings and precautions

Talk to your doctor or nurse before starting treatment with Melfalán Aspen:

• If you are currently receiving or have recently received radiotherapy or chemotherapy.
• If you have any kidney disease.
• If you have recently been vaccinated, or are planning to get vaccinated. This is because certain vaccines (such as the polio, measles, mumps, and rubella vaccines) may cause you an infection if administered while you are being treated with Melfalán Aspen.
• If you are taking combined oral contraceptives (the pill). This is due to the increased risk of venous thromboembolism in patients with multiple myeloma. You should switch to progesterone-only pills with ovulation-inhibiting effect (for example, desogestrel). The risk of venous thromboembolism persists for a period of 4 to 6 weeks after stopping combined oral contraceptives.
• If you are planning to have a child. This is due to the risk of genotoxicity (damage to genetic material) and infertility (see Pregnancy, breastfeeding, and fertility).

Melphalan may increase the risk of developing other types of cancer (e.g., secondary solid tumors, blood cell disorders, or leukemia) 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 prescribing Melfalán.

Thromboembolic events

Thromboprophylaxis should be administered for at least the first 5 months of treatment, especially in patients with additional thrombotic risk factors. The decision to use antithrombotic prophylactic measures should be made after a careful assessment of each patient's individual risk factors.

If a patient experiences any thromboembolic event, treatment should be interrupted and standard anticoagulation therapy should be initiated. Once the patient is stabilized on anticoagulant treatment and complications from the thromboembolic event are under control, treatment with melphalan in combination with lenalidomide and prednisone, or thalidomide and prednisone, or dexamethasone may be restarted at the initial dose, following a benefit/risk assessment. The patient must continue anticoagulant therapy throughout the duration of treatment with melphalan.

Other medicines and Melfalán Aspen

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

Inform your doctor or nurse that you are taking any other medicines, particularly:

• Vaccines containing live organisms (see Warnings and precautions)

• Nalidixic acid (an antibiotic used to treat urinary tract infections)

• Cyclosporine (used to prevent rejection of transplanted organs or tissues, or to treat certain skin conditions such as psoriasis and eczema, or to treat rheumatoid arthritis)

• In children, busulfan (an anticancer medicine)

• Combined oral contraceptives

Pregnancy, lactation and fertility

Pregnancy:

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

Do not take Melfalán Aspen if you or your partner are planning to have a child. Reliable and effective contraceptive measures must be used to prevent pregnancy during treatment with this medicine.

Women should use reliable and effective contraceptive methods during treatment and for 6 months after treatment has ended.

Men should use reliable and effective contraceptive methods during treatment and for 3 months after treatment has ended.

If you are already pregnant, it is important to inform your doctor before using Melfalán Aspen.

Breast-feeding:

Do not take Melfalán Aspen if you are breast-feeding. Consult your doctor for advice.

Fertility:

Melfalán Aspen may affect ovarian function or sperm production, leading to infertility (inability to conceive a baby). In women, menstruation may stop (amenorrhea), and in men, a lack of sperm production (azoospermia) may occur. There is a risk that treatment with Melfalán Aspen may cause sterility in men. Before starting treatment, male patients are advised to seek counseling regarding sperm preservation.

Driving and use of machines

No studies have been conducted on the effects of this medicinal product on the ability to drive or operate machinery.

Melfalán Aspen contains sodium

This medicine contains 46 mg (2 mmol) of sodium (the main component of table/cooking salt) per vial. This corresponds to 2.3% of the maximum daily recommended sodium intake for an adult.

Melfalán Aspen contains ethanol

This medicine contains 5% ethanol (alcohol), equivalent to 0.4 mg per vial, which corresponds to 10 ml of beer or 4.2 ml of wine. This medicine is harmful for individuals suffering from alcoholism. The alcohol content should be taken into account in pregnant or breast-feeding women, children, and high-risk groups such as patients with liver disease or epilepsy.

Melfalán Aspen contains propylene glycol

This medicine contains 62.4 mg of propylene glycol per ml, equivalent to 6 mg/kg. If you are pregnant or breast-feeding, do not take this medicine unless recommended by your doctor. Your doctor may carry out additional monitoring while you are taking this medicine.

If you have hepatic or renal impairment, do not take this medicine unless recommended by your doctor. Your doctor may carry out additional monitoring while you are taking this medicine.

3. How to use Melphalan Aspen

Melphalan Aspen should only be prescribed by a specialist doctor experienced in the treatment of cancer.

Follow exactly the instructions given by your doctor for administering this medicine. If in doubt, consult your doctor, pharmacist, or nurse again.

Melphalan Aspen is an active cytotoxic agent that should only be used under the supervision of physicians experienced in the administration of such agents.

Melphalan Aspen may be administered:

• by infusion into one of your veins
• by infusion into a specific part of your body through an artery.

Your doctor will decide the amount of Melphalan Aspen you should receive. The dose of Melphalan Aspen depends on:

• your body weight or body surface area (a specific measurement that takes into account both weight and height)
• other medicines you are taking
• your illness
• your age
• if you have kidney problems.

From time to time while you are receiving Melphalan Aspen, your doctor will ask you to have a blood test. This is to monitor your blood cell counts and adjust the dose if necessary.

Use in children

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

Use in elderly patients

There are no specific dose adjustments required for elderly patients.

Use in patients with renal impairment

If you have kidney problems, your doctor will usually give you a lower dose than that given to other adults.

If you receive more Melphalan Aspen than you should

Your doctor will indicate the correct dose of Melphalan Aspen to be administered, so it is unlikely that you will receive an excessive amount. If you think you have received more Melphalan Aspen than you should, or if you have missed a dose, inform your doctor or nurse immediately.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 91 562 04 20, indicating the medication and the amount ingested.

If you forget to use Melphalan Aspen

Your doctor will administer the melphalan dose, so it is unlikely that a dose will be missed. If you believe a dose has been missed, the next dose will be given at the next scheduled time. Do not use a double dose to make up for a missed dose.

If you stop treatment with Melphalan Aspen

If you think you should stop using this medicine, consult your doctor first. If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Contact your doctor immediately or go to hospital if you notice any of the following effects:

• Allergic reaction which may include:

  a rash, lumps or hives on the skin
  swelling of the face, eyelids or lips
  sudden onset of "wheezing" and chest tightness
  collapse (due to cardiac arrest).

• Fever or signs of infection (sore throat, mouth sores, or urinary problems).

• Unexpected bleeding or bruising, or feeling tired, faint, or short of breath (this could indicate insufficient production of a specific type of blood cells).

• If you have painful, stiff, or weak muscles and your urine appears darker than usual or has a brown or reddish colour (when Melfalan Aspen is administered directly into the arm or leg).

Consult your doctor if you experience any of the following while taking this medicine:

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

• Decrease in blood cell and platelet counts.
• Nausea, vomiting, and diarrhoea.
• Mouth ulcers (at high doses of Melfalan Aspen).
• Hair loss (at high doses of Melfalan Aspen).
• Tingling or sensation of warmth during administration of Melfalan Aspen.
• Muscle problems such as atrophy and pain (when Melfalan Aspen is administered directly into the arm or leg).

Common (may affect up to 1 in 10 people)

• Hair loss – with usual doses of Melfalan Aspen.
• High levels in the blood of a chemical substance called urea – in people with kidney problems being treated for myeloma.
• A muscle condition that may cause pain, tightness, tingling, burning, or numbness – known as compartment syndrome. This may occur when Melfalan Aspen is administered directly into the arm or leg.

Rare (may affect up to 1 in 1,000 people)

• A condition characterised by a low number of red blood cells due to their premature destruction – which may cause fatigue, shortness of breath, or feeling faint, and may cause headaches or make your skin or eyes appear yellow.
• Lung problems causing cough, wheezing, and difficulty breathing, which in some cases may be severe.
• Liver problems which may show up in blood tests or cause jaundice (yellowing of the eyes and skin).
• Mouth ulcers (at normal doses of Melfalan Aspen).
• Skin rashes or itching.
• Hypersensitivity.

Frequency not known: (frequency cannot be estimated from available data)

• Leukaemia – blood cancer and MDS (abnormalities in blood cell production).
• In women: cessation of menstrual periods (amenorrhoea).
• In men: absence of sperm in semen (azoospermia).
• Muscle tissue death (muscular necrosis).
• Breakdown of muscle fibres (rhabdomyolysis).
• Deep vein thrombosis (formation of a blood clot called thrombus in a deep vein, mainly in the legs) and pulmonary embolism (a blockage in the main pulmonary artery or its branches caused by a blood clot that has broken loose and travelled to the lung).
• Acute kidney injury or renal failure (significant deterioration in kidney function) occurring over a short period of time.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Melphalan Aspen

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 container after EXP. The expiry date refers to the last day of the month indicated.

Store below 30°C. Keep the vial in the outer packaging to protect it from light.

A healthcare professional will prepare Melphalan Aspen for use. Once prepared, it should be administered immediately and must not be stored or refrigerated.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Melfalán Aspen

The active substance is melphalan. Each vial of lyophilized powder contains 50 mg of melphalan (hydrochloride).

The other components are:

• Vial of powder: Hydrochloric acid and povidone K12.
• Vial of solvent: Sodium citrate, propylene glycol, ethanol (5%), and water for injections.

Appearance of the product and contents of the pack

Each pack contains one vial of melphalan powder and one vial of solvent. The powder vial contains 50 mg of the active substance melphalan in powder form, and the solvent vial contains 10 ml of solvent for reconstitution (dissolving) the powder. After reconstitution with 10 ml of solvent, the resulting solution contains 5 mg/ml of anhydrous melphalan.

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder:

Aspen Pharma Trading Limited
3016 Lake Drive,
Citywest Business Campus,
Dublin 24, Ireland
Tel: +34 952 010 137

Manufacturer:

Cenexi – Laboratories Thissen S.A.
Rue de la Papyree 2-4-6
Braine-L’Alleud, 1420
Belgium

Local Representative:

Aspen Pharmacare España S.L.
Avenida Diagonal, 512
Planta Interior 1, Oficina 4
08006 Barcelona
Spain

Date of the most recent review of this leaflet: January 2025

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

INSTRUCTIONS FOR USE AND HANDLING FOR HEALTHCARE PROFESSIONALS

Melfalán Aspen must be prepared at room temperature by reconstituting the lyophilized powder with 10 ml of the supplied solvent-diluent, shaking until completely dissolved. The resulting solution contains the equivalent of 5 mg/ml of anhydrous melphalan at a pH of approximately 6.5.

The Melfalán Aspen solution has limited stability and must be prepared immediately before use. Any unused solution must be discarded.

The reconstituted solution must not be refrigerated, as precipitation will occur.

If Melfalán is administered at room temperature of approximately 25°C, the total time from preparation of the injectable solution to completion of infusion must not exceed 1.5 hours.

If cloudiness or visible crystallization is observed in reconstituted or diluted solutions, the preparation must be discarded.