Prospecto: Information for the User

Alkeran 2Film-Coated Tablets

melfalán

Read this entire prospect carefully before starting to take this medicine, as 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 or nurse.
• This medicine has been prescribed only for you, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.

1.What Alkeran is and for what it is used

2.What you need to know before starting to take Alkeran

3.How to take Alkeran

4.Possible adverse effects

5.Storage of Alkeran

6.Contents of the package and additional information

Alkeran tablets contain a medication called melphalan that belongs to a group of medications called cytotoxics (also known as chemotherapy) and is used to treat certain types of cancer. It works by reducing the number of abnormal cells that your body produces.

Alkeran tablets are used for:

• Multiple myeloma– a type of cancer that develops from cells of the bone marrow called plasma cells. Plasma cells help fight infections and diseases by producing antibodies.
• Advanced ovarian cancer
• Advanced breast cancer
• Polycythemia vera– a type of blood cancer in which the number of red blood cells in the blood increases due to an uncontrolled production of the same in the body. This makes the blood thicker and forms blood clots, causing headaches, dizziness, and difficulty breathing.

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

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

Do not take Alkeran:

• if you are allergic to melphalan 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 pharmacist before taking Alkeran.

Warnings and precautions

Consult your doctor or nurse before starting to take Alkeran:

• if you are currently receiving or have recently received radiation therapy or chemotherapy,
• if you have any kidney disease,

• if you have recently been vaccinated or are planning to be vaccinated. This is because vaccines (such as the polio, measles, mumps, and rubella vaccine) may cause infection if administered while you are being treated with melphalan,
• if you are using 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.
• 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 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 Alkeran.

If you have doubts about whether the information above affects you, consult your doctor or pharmacist before taking Alkeran.

Other medications and Alkeran

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

Inform your doctor if you are taking any other medication, particularly:

• vaccines that contain live microorganisms (see Warnings and precautions)
• nalidixic acid (an antibiotic used to treat urinary tract infections)
• ciclosporin (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 (another chemotherapy medication used to treat certain types 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 using this medication.

Do not recommend treatment with Alkeran during pregnancy because it may cause permanent damage to the fetus. Do not take Alkeran if you are planning to have a child. This affects both men and women. Reliable and effective contraceptive methods should be used to avoid pregnancy while one of the partners is taking this medication.

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

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

If you are already pregnant, it is essential to consult your doctor before starting to take Alkeran.

Your doctor will consider the risks and benefits of taking Alkeran for you and your baby.

You should not take Alkeran if you are breastfeeding. Ask your doctor for advice.

Fertility

Melphalan may affect the ovaries and sperm, leading to infertility (inability to conceive a child). In women, it may cause amenorrhea (cessation of menstruation), and in men, it may result in azoospermia (absence of sperm). Due to the possibility that melphalan treatment may cause sterility in men, it is recommended that they seek advice on sperm preservation before treatment.

Driving and operating machinery

The effects of this medication on the ability to drive and operate machinery have not been studied in patients taking it.

Only a specialist doctor with experience in cancer treatment can prescribe Alkeran for you.

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

Follow exactly the administration instructions for this medication indicated by your doctor. It is essential to take the medication at the correct time. The label on the packaging will tell you how many tablets to take and how often. If the label does not indicate this or if you have doubts, consult with your doctor, nurse, or pharmacist.

• Swallow the tablets whole with a glass of water.
• Do not break, crush, or chew the tablets.

The dose of Alkeran will depend on the type of blood disorder or cancer (see section 1).

Your doctor may also change the dose during treatment, depending on your needs. The dose may sometimes vary if you are an elderly person or have kidney problems.

When taking Alkeran, your doctor will make regular blood tests. This is to check the number of blood cells. Your doctor may change the dose based on the results of these tests.

Thromboembolic events

You may be at an increased risk of deep vein thrombosis (formation of a blood clot called a thrombus within a deep vein, predominantly in the legs) and pulmonary embolism (a blockage of the main pulmonary artery or its branches by a blood clot that breaks loose and travels to the lungs)when melfalan is used in combination with other medications that can affect the functioning of the immune system (such as lenalidomide/talidomide) and others that can increase the benefits of treatment with melfalan (such as prednisone/dexamethasone).

Your doctor will determine what measures should be taken after a careful evaluation of your underlying risk factors (such as smoking, high blood pressure, high levels of lipids in the blood, history of thrombosis).

If you develop any signs or symptoms of thromboembolism (such as difficulty breathing, chest pain, swelling of arms or legs), consult your doctor immediately. If you experience any thromboembolic event, your doctor may decide to interrupt your treatment and start with standard anticoagulant therapy. Your doctor will decide whether to start again with melfalan in combination with lenalidomide and prednisone or talidomide and prednisone or dexamethasone, once thromboembolic events have been controlled.

Neutropenia and thrombocytopenia

An increase in blood toxicity, such as neutropenia (a decrease in the number of white blood cells, which can increase the risk of infections) andtrombocytopenia(a low number of platelets, which can cause bleeding and the formation of hematomas) has been seen when melfalan is used in combination with other medications that can affect the functioning of the immune system (such as lenalidomide/talidomide) and others that can increase the benefits of treatment with melfalan (such as prednisone/dexamethasone).

Multiple myeloma

• The recommended dose is 0.15mg per kilogram of body weight per day for 4days. Treatment is repeated every 6weeks.

Advanced ovarian adenocarcinoma

• The recommended dose is 0.2mg per kilogram of body weight per day for 5days. Treatment is repeated every 4to 8weeks.

Advanced breast cancer

• The recommended dose is 0.15mg per kilogram of body weight per day for 5days. Treatment is repeated every 6weeks.

Polycthemia vera

• The initial dose is between 6and 10mg per day for between 5and 7days. The dose is then reduced to between 2 and 4 mg per day.

Use in children

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

If you take more Alkeran than you should

If you take moreAlkeranthan you should, inform your doctor immediately or go to the hospital directly. Bring the packaging of the medication with you.

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 forget to take Alkeran

Inform your doctor.Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Alkeran

If you have any other doubts about the use of this medication, ask your doctor or nurse.

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

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

• allergic reaction, symptoms may include:

• skin rash, bumps, or blisters
• swollen face, eyelids, or lips
• sudden onset of "wheezing" and chest tightness
• syncope (due to cardiac arrest)

• any sign of high temperature or infection (sore throat, mouth pain, or urinary problems).

The melfalan treatment can cause a decrease in the number of white blood cells. White blood cells fight infections, and when there are very few, an infection can occur.

• any unexpected hematoma or bleeding or feeling extremely tired, dizzy, or short of breath, as this could mean that too few blood cells of a certain type are being produced
• ifsuddenlynot feeling well (even with a normal temperature).
• if experiencing any of the signs/symptoms that may be related to a thromboembolic event (such as difficulty breathing, chest pain, swelling of arms or legs) especially if being treated with melfalan in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone.

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

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

• decrease in the number of blood cells and platelets
• nausea, vomiting, and diarrhea – with high doses of this medicine
• mouth ulcers – with high doses of this medicine
• hair loss – with high doses of this medicine

Common (may affect up to 1 in 10 people)

• hair loss – with regular doses of this medicine
• high levels of a chemical substance called urea in the blood – in people with kidney problems being treated for multiple myeloma.

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

• a condition in which there are too few red blood cells, as they are being destroyed prematurely – this can make you feel very tired, short of breath, and dizzy, and can cause headaches or yellow discoloration of the skin or eyes
• lung problems that can make you cough or produce sibilant sounds and make breathing difficult
• liver problems that can be shown in blood tests or cause jaundice (yellow discoloration of the whites of the eyes and skin)
• mouth ulcers – with normal doses of this medicine
• skin eruptions or skin itching

Unknown frequency (frequency cannot be estimated from available data)

• leukemia – blood cancer
• in women: disappearance of menstruation (amenorrhea)
• in men: absence of sperm in semen (azoospermia)
• deep vein thrombosis and pulmonary embolism
• acute kidney injury or renal insufficiency (significant deterioration of kidney function) that occurs in a short period of time

If any of the side effects become severe, or if you notice any side effect not included 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 hematomas. This disease can also be detected through 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 Alkeran, but only your doctor can tell you if that is the case.

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, 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.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the bottle and the box after ‘CAD’. The expiration date is indicated as month and year and corresponds to the last day of the month indicated.
• Store in the refrigerator (between 2°C and 8°C).
• If your doctor tells you to stop taking the tablets, it is important that you return all the ones that have been left over to your pharmacist, who will destroy them according to the guidelines for the disposal of hazardous substances. Only store the tablets if your doctor instructs you to do so.
• Medications should not be thrown away through drains or in the trash. Deposit the containers and medications that you do not need at the Sigre Pointof the pharmacy. In case of doubt, ask your pharmacist how to dispose of the containers and medications that you do not need. In this way, you will help protect the environment.

Composition of Alkeran

Appearance of the product and contents of the packaging

Alkeran tablets are white to off-white coated tablets, round, biconvex, with the imprint ‘GX EH3’ on one side and ‘A’ on the other. They are presented in bottles of 25and 50 tablets.

Only some packaging sizes may be commercially available.

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

Phone:+34 952 010 137

Responsible formanufacturing:

EXCELLA GmbH & Co. KG,

Nürnberger Strasse 12, 90537 Feucht,

Germany

Local representative:

Aspen Pharmacare España S.L.

Avenida Diagonal, 512

Ground Floor, Office 4

08006 Barcelona

Spain

Last review date of this leaflet: January 2024

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