Prospect: information for the patient

Melfalán Zentiva 50 mg powder and solvent for injectable solution and for infusion EFG

Read this prospect carefully before starting to use this medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• If you experience adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

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

2. What you need to know beforethey administerMelfalán Zentiva

3. Howto administerMelfalán Zentiva

4. Possible adverse effects

5. Storage of Melfalán Zentiva

6. Contents of the package and additional information

MelfalánZentiva contains melfalán as its active ingredient. Melfalán belongs to a group of medicines called cytotoxics (also known as antineoplastic agents). Melfalán is used for the treatment of cancer. It acts by reducing the number of cancerous cells produced by the body.

Melfalán Zentiva is used for:

• Multiple myeloma – a type of cancer that develops in the cells of the bone marrow called plasma cells. Plasma cells help fight infections and diseases by producing antibodies.
• Advanced ovarian carcinoma.
• Infantile neuroblastoma - cancer of the nervous system.
• Malignant melanoma – skin cancer.
• Soft tissue sarcoma – cancer of muscles, fat, fibrous tissue, blood vessels, or other supporting tissues of the body

You should consult a doctor if you want more information about these diseases.

You should consult your doctor if you worsen or do not improve.

You will not be administered Melfalán Zentiva if

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

If you are unsure, consult your doctor or nurse before administration of melfalán.

Warnings and precautions

Before treatment with Melfalán, inform your doctor if any of the following cases apply to you::

• you are currently receiving or have recently received radiation therapy or chemotherapy,
• you have any kidney disease,
• you have been recently vaccinated or are planning to be vaccinated. This is because some vaccines (such as polio, measles, mumps, and rubella) may cause infection if administered while being treated with melfalán,
• you have a blood clot in your leg (thrombosis), lung (pulmonary embolism), or any other part of your body, or have had one in the past,
• you have a condition that increases the likelihood of blood clots forming in your arteries,
• you are taking combined oral contraceptives (the pill). This is due to an increased risk of venous thromboembolism (a blood clot that forms in a vein and moves to another location) in patients with multiple myeloma.

Melfalán may increase the risk of developing another type of cancer (e.g., solid secondary tumors) in a small number of patients, particularly when used in combination with lenalidomide, thalidomide, and prednisone. Your doctor will carefully evaluate the risks and benefits when prescribing melfalán.

Men receiving melfalán should not father children during treatment or for 3 months after.

If you are unsure whether the information above affects you, consult your doctor or pharmacist before taking melfalán.

Other medications and Melfalán Zentiva

Inform your doctor or nurse if you are taking or have taken any other medication, including over-the-counter medications. This includes herbal medications.

In particular, inform your doctor if you are using medications such as:

• other cytostatic agents (antineoplastic agents)
• nalidixic acid (antibiotic used to treat urinary tract infections)
• ciclosporin (used to prevent rejection after a transplant, to treat some skin conditions such as psoriasis and eczema, or to treat rheumatoid arthritis)
• vaccines containing live microorganisms (see Warnings and precautions)
• in children, busulfan (used to treat a certain type of cancer)

Pregnancy, breastfeeding, and fertility

Pregnancy and breastfeeding

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

Pregnancy

During pregnancy, treatment with melfalán is not recommended as it may cause harm to the fetus.Do not take melfalán if you are planning to have a child.This affects both men and women.Effective contraceptive measures should be used to avoid pregnancy while you or your partner are receiving this medication.

If you are already pregnant, it is essential to consult your doctor before melfalán is administered. Your doctor will consider the risks and benefits of treatment with melfalán for you and your baby.

Breastfeeding

The excretion of melfalán in breast milk is unknown. Do not breastfeed while receiving Melfalán.

Fertility

Melfalán may affect the ovaries and sperm, leading to infertility (inability to conceive a child). In women, menstruation may stop (amenorrhea), and in men, there may be a complete absence of sperm (azoospermia) as a result of treatment with melfalán. Therefore, men should consult about sperm preservation before treatment.

Male and female contraception

Women of childbearing age should use effective contraceptive measures during treatment with melfalán and for 6 months after treatment is completed.

It is recommended that men receiving melfalán not father children during treatment and for 3 months after. Discuss using effective and reliable contraceptive methods with your doctor.

Driving and operating machinery

The effects on the ability to drive or operate machinery in patients taking this medication have not been studied. It is not expected that this medication will affect the ability to drive or operate machinery.

Melfalán Zentiva contains sodium

This medication contains 53.5 mg of sodium per vial (main component of table salt/for cooking) in each vial. This corresponds to 2.7% of the maximum daily sodium intake recommended for an adult.

Melfalán Zentiva contains ethanol

This medication contains 5% ethanol (alcohol), which corresponds to 424.3 mg per vial, equivalent to 4.79 ml of beer or 1.99 ml of wine.

This medication is harmful to individuals with alcoholism.

The alcohol content should be taken into account in the case of pregnant women, children, and high-risk groups, such as patients with liver disease or epilepsy..

The amount of alcohol in this medication may alter the effect of other medications.

The amount of alcohol in this medication may affect your ability to drive and operate machinery due to its potential to alter your judgment and reaction time.

Melfalán Zentiva contains propylene glycol

This medication contains 6.2 g of propylene glycol in each vial.

The propylene glycol in this medication may produce effects similar to those caused by drinking alcohol and increase the likelihood of these adverse effects.

Do not use this medication in children under 5 years old.

Use this medication only if recommended by a doctor.

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 will only be administered by experienced medical doctors or nurses in chemotherapy.

Melfalán is an active cytotoxic agent that should only be used under the direction of experienced doctors in the administration of such agents.

Administration Form

Melfalán can be administered:

• as an infusion (drip) into one of its veins.
• in an artery, administered to a specific part of the body (perfusion).

How much Melfalán is administered

Your doctor will decide the dose of Melfalán that you should receive. The treatment dose will depend on:

• your weight or body surface area (a specific measure that takes into account your weight and size),
• other medications you are taking,
• the disease being treated,
• your age,
• if you have kidney problems.

Periodically, your doctor will instruct you to have a blood test to check your blood count, and adjust the dose if necessary.

Use in children

Melfalán is rarely indicated in children. There are no available dosage guidelines for children.

Use in elderly patients

There are no specific dose adjustments for this age group.

Use in patients with renal insufficiency

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

If you are given more Melfalán Zentiva than you should

Your doctor will administer the Melfalán dose, so it is unlikely that you will receive too much dose. If you think you have been given too much or a dose has been forgotten, inform your doctor or nurse.

If you forget to use Melfalán Zentiva

Your doctor will administer Melfalán, so it is unlikely that you will miss a dose. If you think you have forgotten a dose, skip that dose and the next dose will be administered at the next scheduled hour. Do not use a double dose to compensate for a missed dose.

If you interrupt treatment with Melfalán Zentiva

If you think you should stop using this medication, consult your doctor first.

If you have any doubts about the use of this medication, consult your doctor or pharmacist.

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

Severe side effects

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

• Allergic reaction, symptoms may include:
• • Rash, bumps, or blisters on the skin
  • Swollen face, eyelids, or lips
  • Sudden onset of "wheezing" and chest tightness
  • Syncope (due to cardiac arrest)
• Any sign of fever or infection (sore throat, mouth pain, or urinary problems)
• The melfalan treatment can cause a decrease in white blood cells. White blood cells fight infections and when there are very few, an infection may occur.
• Any unexpected bruising or bleeding or feeling extremely tired, dizzy, or short of breath, as this could mean that very few blood cells of a certain type are being produced.
• Feeling unwell suddenly (even with a normal temperature)
• Muscle pain, stiffness, or weakness and urine that appears darker than normal or has a brown or reddish color – when melfalan is administered directly into the arm or leg.
• Experiencing any of the signs/symptoms that may be related to blood clotting (thromboembolic event), such as difficulty breathing, chest pain, swelling of arms or legs, especially if you are being treated with melfalan in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone.
• When melfalan is injected directly into the arm or leg, it is possible that some of the medicine may leak onto surrounding tissues and may damage that tissue. Symptoms of this include mild discomfort in the area, mild skin redness, or mild rash. In rare cases, skin necrosis, ulcers, and deeper tissue damage may occur.

Consult your doctor if you have any of the following side effects that may also occur with this medicine:

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

• Decrease in white blood cells and platelets
• Nausea, vomiting, and diarrhea – with high doses of melfalan
• Mouth ulcers (with high doses of melfalan)
• Hair loss (with high doses of melfalan)
• A sensation of tingling or warmth where melfalan has been injected
• Muscle problems such as atrophy and pain – when melfalan is administered directly into the arm or leg

Common side effects (may affect up to 1 in 10 people):

• Hair loss with usual doses of melfalan.
• 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 called compartment syndrome. This may occur when melfalan is administered directly into the arm or leg.
• Inflammation of the soft tissue that covers the stomach (gastrointestinal mucosa)

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

• Acute renal insufficiency.

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

• A condition in which there are low red blood cell counts, as they are being destroyed prematurely – this can make you feel extremely tired, short of breath, and dizzy and may cause headaches or yellowing of the skin or eyes
• Pulmonary problems that may cause coughing or wheezing and difficulty breathing
• Hepatic problems that may show up in blood tests or cause jaundice (yellowing of the whites of the eyes and skin)
• Mouth ulcers with usual doses of melfalan
• Skin rashes or itching.

Unknown frequency (cannot be estimated from available data):

• Leukemia (blood cancer)
• In women: disappearance of menstruation (amenorrhea)
• In men: absence of sperm in semen (azoospermia)
• Muscle tissue death (muscle necrosis)
• Breakdown of muscle fibers (rhabdomyolysis)
• Formation of a blood clot (thrombus) in a deep vein, mainly in the legs (deep vein thrombosis) and blockage of a pulmonary artery (pulmonary embolism)

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

The use of melfalan may increase the risk of developing another type of cancer called secondary acute leukemia (blood cancer) in the future. Secondary acute leukemia causes the bone marrow (tissue in the bones that produces red and white blood cells) to produce a large number of cells that do not function properly. Symptoms of this disease include fatigue, fever, infection, and bruising. This disease can also be detected by a blood test that will show if there are a large number of cells in the blood that are not functioning properly and very few cells that are.

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

Reporting side effects

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

Keepthis medicationout of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears onthe packagingdafter CAD.The expiration date is the last day of the month indicated.

This medication does not require any special temperature for conservation

Store the vial in the outer packaging to protect it from light.

Melfalán must be prepared by a healthcare professional. Once the solution is reconstituted, it must be used immediately.The disposal of unused medication and all materials that have come into contact with it, will be carried out in accordance with local regulations.

Composition of Melfalán Zentiva

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

The other components (excipients) are:

Vial with powder:povidone K anddiluted hydrochloric acid.

Vial with solvent: contains water for injectable preparations,sodium citrate dihydrate, propylene glycol and ethanol.

Melfalán is dissolved in a solvent before being administered.

Appearance of the product and contents of the package

Each package contains a vial with powder and a vial with solvent.

The vial with powder contains 50 mg of the active substance melfalán in powder and the vial with solvent contains 10 ml of solvent that serves to reconstitute (dissolve) the powder.

When the melfalán powder vial is reconstituted with the 10 ml of solvent, the resulting solution contains 5mg/ml of anhydrous melfalán.

Powder:glass type I transparent vial with a bromobutyl rubber stopper coated with omniflex 3G and aluminum flip-off cap with a polypropylene cap of orange color and matte finish. The vials may or may not have retractable sleeves.

Each package contains 1 vial with 50 mg of melfalán.

Solvent:glass type I transparent vial with a bromobutyl rubber stopper coated with omniflex 3G and aluminum flip-off cap with a polypropylene cap of orange color and matte finish.

Each package contains 1 vial of 10 ml.

Marketing Authorization Holder:

Zentiva, k.s.,

U kabelovny 130,

Praga 10 – Dolní Mecholupy,

102 37 Czech Republic

Responsible for manufacturing:

SGS Pharma Magyarorszag Kft.

Derkovits Gyula Utca 53,

Budapest XIX,1193,

Hungary

or

Tillomed Malta Limited,

Malta Life Sciences Park,

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000, Malta

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Zentiva Spain S.L.U.

Avenida de Europa, 19, Edificio 3, Planta 1.

28224 Pozuelo de Alarcón, Madrid

Spain

This medicine is authorized in the member states of the European Economic Areaand in the United Kingdom (Northern Ireland) with the following names:

United Kingdom (Northern Ireland):Melphalan 50 mg Powder and Solvent for Solution forInjection/Infusion

Germany:Melphalan Tillomed 50 mg Pulver und Lösungsmittel zur Herstellung einer Injektions Infusionslösung

Italy:Melfalan Tillomed

Spain:Melfalán Zentiva 50 mg powder and solvent for injectable solution and for perfusion EFG

Cyprus:Melphalan Tillomed 50 mg

Greece:Melphalan Tillomed 50 mg

Last review date of thisleaflet:March 2024

The detailed information of this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)

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This information is intended solely for healthcare professionals:

Procedures for the proper handling and disposal of cytotoxic medicines must be followed:

1. Employees must be instructed in the reconstitution of the medicine.
2. Pregnant women must be excluded from handling this medicine
3. Staff must wear appropriate protective clothing, including masks, safety glasses, and gloves when reconstituting the preparation.
4. Any item used for administration or cleaning, including gloves, must be disposed of in containers for contaminated waste that is incinerated at high temperature. Liquid waste can be disposed of with abundant water.

In case of accidental contact with the eyes with Melfalán, rinse immediately with a sodium chloride solution or abundant water and consult a doctor immediately. In case of skin contact, wash the affected areas immediately with soap and cold water and consult a doctor immediately. The spilled solution must be cleaned immediately with a wet absorbent paper, which must then be disposed of safely. Contaminated surfaces must be washed with abundant water.

Reconstitution

Melfalán must be prepared at room temperature (approximately 25°C), reconstituting the powder with the provided solvent-diluent.

It is essential that both the powder and the provided solvent be at room temperature (approximately 25 °C) before starting the reconstitution.

10 ml of solvent must be added quickly to the vial containing the powder as a single quantity using sterile needles and syringes. A needle of caliber 21 or higher must be used to pierce the stopper of the vial during reconstitution. For a smooth and effective penetration, the needle must be inserted perpendicularly into the stopper, neither too quickly nor too brusquely, without twisting. The vial must be shaken vigorously immediately (for approximately 5 minutes) until a transparent solution is obtained, without visible particles. It is essential to add the diluent quickly followed by immediate vigorous shaking for proper dissolution.

The agitation of the formulation produces a significant amount of very small air bubbles. These bubbles may remain for 2 to 3 minutes since the resulting solution is quite viscous. This may make it difficult to evaluate the clarity of the solution.

Each vial must be reconstituted individually in this way. The resulting solution contains the equivalent of 5 mg per ml of anhydrous melfalán. If the steps for preparation mentioned above are not followed, incomplete dissolution of melfalán may occur.

The melfalán solution has limited stability and must be prepared immediately before use.

The reconstituted solution must not be refrigerated as this will cause precipitation.

Mixing

Mix 10 ml of the previously reconstituted solution with a concentration of 5 mg/ml of anhydrous melfalán in a perfusion bag containing 100 ml of 0.9% sodium chloride solution for injection. Mix well this diluted solution to obtain a nominal concentration of 0.45 mg/ml of anhydrous melfalán.

When further diluted in a perfusion solution, melfalán has reduced stability and the degradation rate increases rapidly with increasing temperature.If melfalán is administered at a room temperature of approximately 25 °C, the maximum time from preparation of the solution to completion of the perfusion must not exceed 1.5 hours.

Melfalán is not compatible with perfusion solutions containing dextrose and it is recommended to use only 9 mg/ml sodium chloride solution for injection (0.9%).

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

Disposal

Any unused solution after 1.5 hours must be disposed of according to standard guidelines for handling and disposal of cytotoxic medicines.

Any unused medicine or waste must be disposed of according to local requirements for cytotoxic medicines.