ALKERAN 2 MG FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Alkeran 2mg film-coated tablets

melfalán

Read all of this leaflet carefully before you start taking 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 pharmacist.
• 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 pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Alkeran and what is it used for
2. What you need to know before you take Alkeran
3. How to take Alkeran
4. Possible side effects
5. Storing Alkeran
6. Contents of the pack and further information

1. What is Alkeran and what is it used for

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

Alkeran tablets are used for:

• Multiple myeloma– a type of cancer that develops from cells in the bone marrow called plasma cells. Plasma cells help to fight infections and diseases by producing antibodies.
• Ovarian canceradvanced
• Breast canceradvanced.
• Polycythaemia rubra vera– a type of blood cancer where the number of red blood cells in the blood increases due to uncontrolled production in the body. This makes the blood more viscous and leads to blood clots, causing headaches, dizziness, and difficulty breathing.

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 take Alkeran

Do not take Alkeran:

• 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 pharmacist before taking Alkeran.

Warnings and precautions

Consult your doctor or nurse before starting Alkeran:

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

• if you have been vaccinated recently or are planning to be vaccinated. This is because vaccines (such as polio, measles, mumps, and rubella) could give you an infection if they are given while you are being treated with melfalán,
• if you are using combined oral contraceptives (the pill). This is due to the 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, breast-feeding, and fertility).

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

If you have any doubts about whether what you have read affects you, consult your doctor or pharmacist before taking Alkeran.

Other medicines and Alkeran

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

Tell your doctor if you are taking any other medicine, in particular:

• vaccines that contain live microorganisms (see Warnings and precautions)
• nalidixic acid (an antibiotic used to fight urinary infections)
• cyclosporin (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 chemotherapeutic agent used to treat certain types of cancer)

Pregnancy, breast-feeding, and fertility

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Treatment with Alkeran is not recommended 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 measures should be used to avoid pregnancy while one partner is taking this medicine.

Women should use reliable and effective contraceptive methods during treatment and for up to 6 months after finishing treatment.

Men should use reliable and effective contraceptive methods during treatment and for up to 3 months after finishing treatment.

If you are already pregnant, it is essential that you consult your doctor before starting 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 breast-feeding. Ask your doctor for advice.

Fertility

Melfalán may affect the ovaries and sperm, which can cause infertility (inability to conceive a child). In women, menstruation may disappear (amenorrhea), and in men, there may be a complete lack of sperm (azoospermia). Due to the possibility that treatment with melfalán may cause sterility in men, it is recommended that they seek advice on sperm preservation before treatment.

Driving and using machines

The effects of this medicine on the ability to drive and use machines have not been studied in patients taking it.

3. How to take Alkeran

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

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

Follow the instructions for administration of this medicine exactly as your doctor has told you. It is important that you take the medication at the right time. The label on the pack will tell you how many tablets to take and when. If the label does not say or if you have any doubts, consult 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 problem 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 elderly or have kidney problems.

When taking Alkeran, your doctor will regularly perform 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

There may be 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 artery of the lung or its branches by a blood clot that breaks loose and travels to the lung) when melfalán is used in combination with other medicines that may affect the functioning of the immune system (such as lenalidomide/thalidomide) and others that may increase the benefits of treatment with melfalán (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 lipid levels 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 standard anticoagulant therapy. Your doctor will decide whether you should start taking melfalán again in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone once the thromboembolic events have been controlled.

Neutropenia and thrombocytopenia

There has been an increase in blood toxicity, such as neutropenia (decrease in the number of white blood cells, which can increase the risk of infection) and thrombocytopenia (low number of platelets, which can cause bleeding and bruising) when melfalán is used in combination with other medicines that may affect the functioning of the immune system (such as lenalidomide/thalidomide) and others that may increase the benefits of treatment with melfalán (such as prednisone/dexamethasone).

Multiple myeloma

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

Advanced ovarian adenocarcinoma

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

Advanced breast carcinoma

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

Polycythaemia rubra vera

• The initial dose is between 6 and 10 mg per day for 5 to 7 days. 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 dosage guidelines available for children.

If you take more Alkeran than you should

If you take more Alkeran than you should, tell your doctor immediately or go to the hospital directly. Take the medicine pack with you.

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

If you forget to take Alkeran

Tell your doctor. Do not take a double dose to make up for forgotten doses.

If you stop taking Alkeran

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

4. Possible side effects

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

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

• allergic reaction, the signs may include:

• a rash, lumps, or hives on the skin
• face, eyelids, or lips swollen
• sudden onset of "wheezing" and tightness in the chest
• fainting (due to cardiac arrest)

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

Treatment with melfalán may cause a decrease in the number of white blood cells. White blood cells fight infections, and when there are too few, an infection can occur.

• any unexpectedbruising 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
• if you suddenlydo not feel well (even with a normal temperature).
• if you experience 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 you are being treated with melfalán 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)

• a 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 usual doses of this medicine
• high levels in the blood of a chemical called urea – in people with kidney problems who are being treated for myeloma.

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

• a disease in which you have a low number of red blood cells, as they are destroyed prematurely – this can make you feel very tired, short of breath, and dizzy, and may cause headaches or yellowing of the skin and eyes
• lung problems that can make you cough or wheeze and make it difficult to breathe
• liver problems that can show up in your blood tests or cause jaundice (yellowing of the whites of the eyes and skin)
• mouth ulcers – with normal doses of this medicine
• skin rash or itching

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

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

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

It is possible that 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. The 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.

Tell your doctor as soon as possible if you have 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 side effects, talk to your doctor or nurse, even if it is possible that they are not listed in this leaflet. You can also report side effects directly to 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. Storing Alkeran

• 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 carton and blister after ‘EXP’. The expiry date refers to the last day of the month stated.
• Store in a 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 remaining tablets to your pharmacist, who will destroy them according to the guidelines for the disposal of hazardous substances. Only keep the tablets if your doctor tells you to.
• Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicinal products in the SIGRE collection point at your pharmacy. If you have any doubts, ask your pharmacist how to dispose of the packaging and any unused medicinal products. This will help protect the environment.

6. Contents of the pack and further information

Composition of Alkeran

• The active substance is melfalán. Each Alkeran tablet contains 2 mg of melfalán.
• The other ingredients are microcrystalline cellulose, crospovidone, anhydrous colloidal silica, magnesium stearate, hypromellose, titanium dioxide (E-171), and macrogol.

Appearance of the product and pack contents

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

Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer

Marketing authorisation holder:

Aspen Pharma Trading Limited

3016 Lake Drive,

Citywest Business Campus,

Dublin 24, Ireland

Tel: +34 952 010 137

Manufacturer:

EXCELLA GmbH & Co. KG,

Nürnberger Strasse 12, 90537 Feucht,

Germany

Local representative:

Aspen Pharmacare España S.L.

Avenida Diagonal, 512

Planta Interior 1, Oficina 4

08006 Barcelona

Spain

Date of last revision of this leaflet: January 2024

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