Package Insert: Information for the User

Melfalán Aspen 50 mg Powder and Diluent for Injectable Solution and for Infusion

melfalán

Read this package insert carefully before you start taking this medicine, because it contains important information for you.

• Keep this package insert, 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 should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this package insert. See section 4.

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

MelfalánAspen is used for:

• Multiple myeloma:a type of cancer that appears 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 systemin children.
• Malignant melanoma:a type of skin cancer.
• Soft tissue sarcoma:cancer of muscle, fat, fibrous tissue, blood vessels, or other supporting tissues of the body.

Ask your doctor if you want to learn more about these diseases.

You should consult a doctor if you get worse or do not improve.

No use Melfalán Aspen:

- If you are allergic to melfalán or any of the other components of this medication (listed in section 6).

- If you are breastfeeding.

If you are unsure, consult your doctor or nurse before starting to use Melfalán Aspen.

Warnings and precautions

Consult your doctor or nurse before starting to use Melfalán Aspen:

• If you are currently receiving or have recently received radiation or chemotherapy.
• If you have any kidney disease.
• If you have been recently vaccinated, or are planning to be vaccinated. This is because some vaccines (such as the polio, measles, mumps, and rubella vaccines) may cause 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 will need to switch to progesterone-only pills with ovulation inhibition (e.g. desogestrel). The risk of venous thromboembolism is maintained for a period of 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, breastfeeding, and fertility).

Melfalán may increase the risk of developing other types of cancer (e.g. 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 will need to 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 initiated. Once the patient is stabilized under anticoagulant treatment and complications from the thromboembolic episode have been controlled, treatment with melfalán in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone can be resumed at the initial dose, after a benefit-risk assessment. The patient should continue anticoagulant therapy while receiving melfalán treatment.

Other medications and Melfalán Aspen

Inform your doctor or nurse if you are using, have used recently, or may need to use any other medication, including those purchased without a prescription. This includes herbal medications.

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

• live vaccines (see Warnings and precautions)

• nalidixic acid(an antibiotic used to treat urinary tract infections)
• ciclosporina (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)
• busulfan (cancer medication) in children
• combined oral contraceptives

Pregnancy, breastfeeding, and fertility

Pregnancy:

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

Do not take Melfalán Aspen if your partner or you are planning to have a child. Reliable and effective contraceptive methods should be used to avoid pregnancy when one of the partners is receiving treatment with this medication.

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

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

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

Breastfeeding:

Do not take Melfalán Aspen if you are breastfeeding. Consult your doctor.

Fertility:

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

Driving and operating machinery

No studies have been conducted on the effects of this medication on the ability to drive and operate machinery.

Melfalán Aspen contains sodium

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

Melfalán Aspen contains ethanol

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

Melfalán Aspen contains propylene glycol

This medication contains 62.4 mg of propylene glycol per ml, equivalent to 6 mg/kg. If you are pregnant or breastfeeding, do not take this medication unless recommended by your doctor. Your doctor may perform additional checks while you are taking this medication.

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

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

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor, pharmacist or nurse again.

Melfalán Aspenis an active cytotoxic agent that should only be used under the direction of doctors with experience in administering such agents.

Melfalán Aspencan be administered:

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

Your doctor will decide how muchMelfalán Aspenyou should receive. The amount ofMelfalán Aspendepends on:

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

From time to time while you are takingMelfalán Aspen, your doctor will ask you to have a blood test. This is to control your blood cell count, and adjust the dose if necessary.

Use in children

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

Use in elderly patients

No specific dose adjustments are available for elderly patients.

Use in patients with renal insufficiency

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

If you receive moreMelfalán Aspenthan you should

Your doctor will indicate the dose ofMelfalánAspenyou should take, therefore, it is unlikely that you will take too much. If you think you are taking moreMelfalán Aspenthan you should or if you have forgotten a dose, inform your doctor or nurse.

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

If you forgot 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 you have forgotten a dose, you will be given the next dose at the next scheduled hour. Do not use a double dose to compensate for missed doses.

If you interrupt treatment with Melfalán Aspen

If you think you should stop using this medication, consult your doctor first. If you have any other doubts about the use of this medication, ask your doctor, pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

• Allergic reaction, which may include:

skin rash, bumps, or hives

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, or urinary problems).
• Bleeding or unexpected bruising or a feeling of fatigue, dizziness, or shortness of breath (this could indicate a lack of a specific type of blood cell).
• If you have muscle pain, stiffness, or weaknessandif your urine appears darker than usualor has a brown or reddish color (whenMelfalán Aspenis administered directly in 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)

• Low blood cell count and platelet count.
• Nausea, vomiting, and diarrhea.
• Mouth ulcers (at high doses ofMelfalán Aspen).
• Hair loss (at high doses ofMelfalán Aspen).
• Tickling or feeling of heat during the administration ofMelfalán Aspen.
• Muscle problems such as atrophy and pain (whenMelfalán Aspenis administered directly in the arm or leg).

Common (may affect up to 1 in 10 people)

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

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

• A disease that presents a low number of red blood cells, as they are destroyed prematurely – it can cause fatigue, shortness of breath, or dizziness and can cause headaches or make your skin or eyes appear yellow.
• Pulmonary problems that cause coughing or wheezing and make breathing difficult, which in some cases can be very serious.
• Liver problems that may be evident in blood tests or cause jaundice (yellowing of the eyes and skin).
• Mouth ulcers (at normal doses ofMelfalán Aspen).
• Skin eruptions or itching.
• Hypersensitivity.

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

• Leukemia – blood cancer and MDS (alterations in blood cell production).
• In women: menstrual period interruption (amenorrhea).
• In men: absence of sperm in 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 moves to the lung).
• Acute kidney injury or renal insufficiency (significant deterioration of renal function) that occurs in a short period of time.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or nurse, even if it is a possible adverse reaction that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es.By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

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.MelfalánAspen. Once prepared, it should be administered immediately and not stored or refrigerated.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

Composition of Melfalán Aspen

The active ingredient is melfalán. Each vial of lyophilized powder contains 50 mg of melfalán (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 injection preparations.

Appearance of the product and contents of the package

Each package contains a vial ofmelfalán powderand a vial of solvent. The vial of powder contains 50 mg of the active ingredient melfalán in the form of powder, and the vial of solvent contains 10 ml of a solvent to reconstitute (dissolve) the powder. After reconstitution with 10 ml of the solvent, the resulting solution contains 5 mg/ml of anhydrous melfalán.

Holder of the marketing authorization and responsible for manufacturing:

Holder of the marketing authorization:

Aspen Pharma Trading Limited

3016 Lake Drive,

Citywest Business Campus,

Dublin 24, Ireland

Tel: +34 952 010 137

Responsible for manufacturing:

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, Office 4

08006 Barcelona

Spain

Last review date of thisleaflet:January 2025

The detailed and updated information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (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 must be prepared, at room temperature, by reconstituting the lyophilized powder with 10 ml of the solvent-diluent provided, 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 solution of Melfalán Aspen has limited stability and must be prepared immediately before use. The solution that is not used must be discarded.

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

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

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