MELPHALAN ASPEN 50 mg POWDER AND SOLVENT FOR INJECTION AND INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

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

melfalán

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• 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.

Contents of the pack

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

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

Melfalán Aspen contains the active substance melfalán, which belongs to a group of medicines called cytotoxics (also called chemotherapy). It is used to treat certain types of cancer. It works by reducing the number of abnormal cells your body produces.

Melfalán Aspen is used for:

• Multiple myeloma:a type of cancer that occurs in the bone marrow cells called plasma cells. Plasma cells help fight infections and diseases by producing antibodies.
• Advanced ovarian cancer.
• Advanced neuroblastoma(a type of cancer that affects 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 supporting tissue of the body.

Ask your doctor if you want more information about these diseases.

You should consult a doctor if it gets worse or does not improve.

2. What you need to know before you use Melfalán Aspen

Do not use Melfalán Aspen:

• If you are allergic to melfalán or any of the other ingredients of this medicine (listed in section 6).
• If you are breast-feeding.

If you are not sure, consult your doctor or nurse before using Melfalán Aspen.

Warnings and precautions

Consult your doctor or nurse before using Melfalán Aspen:

• If you are currently receiving or have recently received radiotherapy or chemotherapy.
• If you have kidney disease.
• If you have been vaccinated recently or are planning to be vaccinated. This is because some vaccines (such as the polio, measles, mumps, and rubella vaccine) can cause infection if administered while being treated with Melfalán Aspen.
• If you are taking combined oral contraceptives. This is due to the increased risk of venous thromboembolism in patients with multiple myeloma. You should switch to progestogen-only pills (such as desogestrel). The risk of venous thromboembolism remains for 4 to 6 weeks after stopping treatment with 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, breast-feeding, and fertility).

Melfalán 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 episodes

Thromboprophylaxis should be administered, at a minimum, during 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 thorough assessment of each patient's risk factors.

If the patient experiences any thromboembolic episode, treatment should be interrupted and standard anticoagulation therapy should be initiated. Once the patient is stabilized under anticoagulant treatment and the complications of the thromboembolic episode are controlled, treatment with melfalán may be restarted in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone with the initial dose, after a benefit-risk assessment. The patient should continue anticoagulant therapy while receiving melfalán.

Other medicines and Melfalán Aspen

Tell your doctor or nurse if you are using, have recently used, or might use any other medicines, including those obtained without a prescription. This includes herbal medicines.

Inform your doctor or nurse that you are taking any other medicine, in particular:

• vaccines containing live organisms (see Warnings and precautions)

• nalidixic acid(an antibiotic used to treat urinary tract infections)
• cyclosporine (used to prevent organ or tissue rejection after a transplant or to treat certain skin diseases such as psoriasis and eczema or to treat rheumatoid arthritis)
• in children, busulfan (anticancer medicine)
• combined oral contraceptives

Pregnancy, breast-feeding, and fertility

Pregnancy:

If you are pregnant or breast-feeding, think you may be pregnant, or plan 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 methods should be used to avoid pregnancy when either partner is receiving treatment with this medicine.

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

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

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

Breast-feeding:

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

Fertility:

Melfalán Aspen may affect the functioning of the ovaries or sperm production, causing infertility (inability to conceive a baby). In women, menstruation may stop (amenorrhea), and in men, there may be a lack of sperm production (azoospermia). There is a risk that treatment with Melfalán Aspen may cause sterility in men. Before starting treatment, male patients are advised to seek advice on sperm preservation.

Driving and using machines

No studies have been performed on the effects of this medicine on the ability to drive and use machines.

Melfalán Aspen contains sodium

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

Melfalán Aspen contains ethanol

This medicine contains 5% ethanol (alcohol), which corresponds to an amount of 0.4 mg per vial, equivalent to 10 ml of beer or 4.2 ml of wine. This medicine is harmful to people with alcoholism. The alcohol content should be taken into account in the case of 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 it is recommended by your doctor. Your doctor may perform additional checks while you are taking this medicine.

If you have liver or kidney failure, do not take this medicine unless it is recommended by your doctor. Your doctor may perform additional checks while you are taking this medicine.

3. How to use Melfalán Aspen

Melfalán Aspen should only be prescribed by a specialist doctor with experience in cancer treatment.

Follow exactly the administration instructions of this medicine given by your doctor. If you are unsure, consult your doctor, pharmacist, or nurse again.

Melfalán Aspen is a cytotoxic agent that should only be used under the direction of doctors with experience in the administration of such agents.

Melfalán Aspen can 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 Melfalán Aspen to be administered to you. The amount of Melfalán Aspen depends on:

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

From time to time while you are taking Melfalán Aspen, your doctor may ask you to have a blood test. This is to check the blood cell count and change the dose if necessary.

Use in children

Melfalán is rarely used in children. Dosage guidelines for children are not available.

Use in elderly patients

There are no specific dose adjustments for elderly patients.

Use in patients with renal impairment

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

If you receive more Melfalán Aspen than you should

Your doctor will tell you the dose of Melfalán Aspen you should take, so it is unlikely that you will take too much. If you think you have used more Melfalán Aspen than you should or have missed a dose, inform your doctor or nurse.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount taken.

If you forget to use Melfalán Aspen

Your doctor will administer the dose of melfalán, so it is unlikely that you will forget a dose. If you think a dose has been forgotten, it will be administered at the next scheduled time. Do not use a double dose to make up for forgotten doses.

If you stop using Melfalán 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 side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Consult your doctor immediately if you notice any of the following:

• Allergic reaction that can include:

a rash, lumps, or hives on the skin

swelling of the face, eyelids, or lips

sudden onset of "wheezing" and tightness in the chest

collapse (due to cardiac arrest).

• Fever or signs of infection (sore throat, mouth, or urinary problems).
• Bleeding or unexpected bruising or feeling tired, faint, or short of breath (this could indicate insufficient production of a specific type of blood cell).
• If you have muscle pain, stiffness, or weakness andif your urine appears darker than usualor has a brown or reddish color (when Melfalán Aspen is administered directly into the arm or leg).

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

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

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

Common (may affect up to 1 in 10 people)

• Hair loss – with usual doses of Melfalán Aspen.
• High levels in the blood of a chemical called urea – in people with kidney problems who are being treated for myeloma.
• A muscle problem that can cause pain, pressure, tingling, burning, or numbness – called compartment syndrome. This can occur when Melfalán Aspen is administered directly into the arm or leg.

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

• A disease that presents with a low number of red blood cells, as they are destroyed prematurely – it can cause tiredness, shortness of breath, or dizziness and can cause headaches or make your skin or eyes appear yellow.
• Lung problems that cause coughing or wheezing and difficulty breathing, which in some cases can be severe.
• Liver problems that can be seen in blood tests or cause jaundice (yellowing of the eyes and skin).
• Mouth ulcers (at normal doses of Melfalán Aspen).
• Skin rashes or itching.
• Hypersensitivity.

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

• Leukemia – blood cancer and myelodysplastic syndrome (disorders of blood cell production).
• In women: interruption of menstrual period (amenorrhea).
• In men: absence of sperm in the semen (azoospermia).
• Muscle tissue death (muscle necrosis).
• Breakdown of muscle fibers (rhabdomyolysis).
• Deep vein thrombosis (formation of a blood clot called a thrombus in a deep vein, mainly in the legs) and pulmonary embolism (a blockage in the main pulmonary artery or its branches by a blood clot that breaks loose and travels to the lung).
• Acute kidney injury or kidney failure (significant deterioration of kidney function) that occurs in a short period.

Reporting of side effects

If you experience any side effects, consult your doctor or nurse, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Melfalán Aspen

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date is the last day of the month stated.

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

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Melfalán Aspen

The active ingredient is melfalán. Each vial of lyophilized powder contains 50 mg of melfalán (hydrochloride).

The other components are:

• Powder vial: Hydrochloric acid and povidone K12.
• Solvent vial: Sodium citrate, propylene glycol, ethanol (5%) and water for injectable preparations.

Appearance of the Product and Container Contents

Each container contains a vial of melfalán powder and a vial of solvent. The powder vial contains 50 mg of the active ingredient melfalán in powder form, and the solvent vial contains 10 ml of a solvent for reconstitution (dissolving) the powder. After reconstitution with 10 ml of the solvent, the resulting solution contains 5 mg/ml of anhydrous melfalán.

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 Last Revision of this Leaflet:January 2025

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

INSTRUCTIONS FOR USE AND HANDLING DIRECTED TO THE HEALTHCARE PROFESSIONAL

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

The Melfalán Aspen solution has limited stability and should be prepared immediately before use. The solution that is not used should be discarded.

The reconstituted solution should not be refrigerated because precipitation will occur.

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

If visible turbidity or crystallization is detected in the reconstituted or diluted solutions, the preparation should be discarded.