BUSULFAN ASPEN 2 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Busulfan Aspen 2 mg film-coated tablets

Busulfan

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, pharmacist, 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 experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet:

1. What is Busulfan Aspen and what is it used for
2. What you need to know before you take Busulfan Aspen
3. How to take Busulfan Aspen
4. Possible side effects
5. Storage of Busulfan Aspen

Contents of the pack and further information

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

Busulfan Aspen contains the active substance busulfan, which belongs to a group of medicines called alkylating agents (a type of cytotoxic or chemotherapy medicine).

This medicine is used to treat certain blood disorders, including some types of cancer. It works by reducing the number of new blood cells produced by your bone marrow.

Busulfan Aspen may be used in combination with other cytotoxic medicines, such as cyclophosphamide.

Busulfan Aspen is used for:

• Chronic myeloid leukemia:a type of cancer that affects certain blood cells (white blood cells) and causes an increase in the number of abnormal white blood cells in the blood. This can cause infections and bleeding.
• Polycythemia vera:a disease that increases the number of red blood cells in the blood. This disease causes the blood to thicken and can lead to blood clots, resulting in symptoms such as headaches, dizziness, and difficulty breathing, etc.
• Thrombocytosis:a disease that affects platelets (cells that help the blood to clot). It can cause an increase in platelets, leading to blood clots. Or, the platelets may not work properly, causing easy bleeding, such as nosebleeds, bleeding gums, and bruising.
• Myelofibrosis:a disease in which the bone marrow is replaced by scar tissue, causing the production of white and red blood cells to be disrupted. This disease can cause symptoms such as fatigue, stomach swelling, bleeding, and bruising.

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

2. What you need to know before you take Busulfan Aspen

Do not take Busulfan Aspen

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

If you are not sure, consult your doctor before taking Busulfan Aspen.

Warnings and precautions

Busulfan Aspen is a potent cytotoxic medicine that can cause a significant decrease in blood cells. At the recommended dose, this is the desired effect. For this reason, strict monitoring is required.

There is a possibility that the use of Busulfan Aspen may increase the risk of developing another malignant tumor in the future.

Vaccination with live vaccines is not recommended.

Talk to your doctor before starting Busulfan Aspen:

• If you have been treated with radiation therapy or chemotherapy, now or recently, or if you have ever undergone a stem cell transplant. This is because patients who took Busulfan Aspen may develop severe liver problems (hepatic veno-occlusive disease). There is a higher risk of developing hepatic veno-occlusive disease if you have received radiation therapy, three or more cycles of chemotherapy, or have undergone a stem cell transplant.
• If you have a high level of uric acid in your blood or suffer from gout, which can cause joint pain.
• If you have any liver, kidney, or lung problems.

Busulfan Aspen may cause infertility in both men and women. Before starting treatment, talk to your doctor about sperm preservation.

Children and adolescents

There are no clinical data available on the safety and efficacy of Busulfan Aspen in adolescents under 18 years of age.

Other medicines and Busulfan Aspen

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Busulfan Aspen may interact with other medicines and should be used with caution.

• Other cytotoxic medicines (chemotherapy): when given with Busulfan Aspen, there is a higher risk of side effects that affect the lungs.
• Phenytoin (used to treat and prevent seizures): your doctor may consider replacing phenytoin with another medicine.
• Live vaccines (such as oral polio vaccine, measles, mumps, and rubella): Busulfan Aspen may cause the body to have a lower ability to fight infections.
• Itraconazole (to treat fungal infections) or metronidazole (to treat bacterial infections), deferasirox (a medicine used to remove excess iron from the body), or ketobemidone (used to treat pain), as these medicines may cause serious side effects if given with Busulfan Aspen.
• Cyclophosphamide (used to treat certain blood disorders): if given with Busulfan Aspen, it is recommended that the first dose of cyclophosphamide be given 24 hours after the last dose of Busulfan Aspen to reduce the risk of any possible side effects.
• If you need anesthesia for surgery in the hospital or at the dental clinic, inform your doctor or dentist that you are taking Busulfan Aspen.
• The use of paracetamol during Busulfan Aspen administration should be done with caution.
• In pediatric patients, in case of busulfan-melphalan administration, if the melphalan dose is given before 24 hours after the last busulfan dose, it may cause toxicity.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

Busulfan Aspen 2 mg film-coated tablets should be avoided whenever possible during pregnancy, especially during the first trimester. The potential risk to the fetus should be weighed against the expected benefit to the mother in each individual case.

Effective contraceptive methods should be used when one partner is being treated with this medicine.

Breastfeeding

You should not take Busulfan Aspen if you are breastfeeding.

Fertility

Busulfan Aspen may damage sperm or eggs, causing infertility in both sexes. It may cause severe ovarian failure, which can prevent puberty in girls and pre-teenagers. In males, it may cause testicular atrophy.

Driving and using machines

No information is available on the effects of Busulfan Aspen on the ability to drive and use machines.

Busulfan Aspen contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Busulfan Aspen

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are not sure, consult your doctor again.

Busulfan Aspen should only be given by a specialist doctor with experience in the treatment of cancer.

Your doctor will tell you how much medicine you need to take and how often you need to take it.

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

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

Your doctor may change the dose during treatment, depending on your needs.

Sometimes the dose may be adjusted if you are overweight.

If you take a high dose of Busulfan Aspen, your doctor may also prescribe another medicine called benzodiazepine to help prevent seizures.

During treatment with Busulfan Aspen, your doctor may perform regular blood tests to check the blood cell count and may adjust the dose of the medicine as needed.

If you take more Busulfan Aspen than you should

Tell your doctor immediately or go to the hospital. Take the medicine pack with you, even if it is empty.

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 taken.

If you forget to take Busulfan Aspen

If you forget to take a dose, tell your doctor. Do not take a double dose to make up for forgotten doses.

4. Possible side effects

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

Some people may be allergic to this medicine. If you experience any of the following symptoms after taking Busulfan Aspen 2 mg film-coated tablets, STOP taking the tablets and tell your doctor immediately:

• Sudden shortness of breath, difficulty breathing, chest pain, or tightness
• Swelling of the eyelids, face, lips, mouth, or tongue
• Uneven skin rash or "hives" anywhere on the body.

Changes in blood cells may occur. Your doctor will perform regular blood tests to check the levels of cells in the blood, but you should tell your doctor immediately if you notice any signs of fever or infection, such as cystitis, or if you have bruising or bleeding unexpectedly.

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

• A decrease in the number of blood cells and platelets
• Feeling unwell (nausea), vomiting, diarrhea, and mouth ulcers: with high doses of Busulfan Aspen
• Jaundice (yellowing of the skin or whites of the eyes), liver and bile duct damage: with high doses of Busulfan Aspen and increased bilirubin
• In women, menstruation may stop, fertility may be affected, and early menopause may occur: with high doses of Busulfan Aspen
• In girls, the onset of puberty may be delayed or stopped
• In children and men, sperm production may be delayed, reduced, or stopped, and testicular size may be reduced
• Inflammation of the lungs without signs of infection (pneumonia syndrome) with high doses of Busulfan Aspen

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

• The heart may not beat normally (especially if you have a hereditary blood disease called thalassemia) with high doses of Busulfan Aspen
• Inflammation of the lungs that causes difficulty breathing, coughing, and an increase in temperature (pneumonitis)
• Hair loss: with high doses of Busulfan Aspen
• Appearance of dark spots on the skin
• Blood in the urine and pain when urinating (bladder inflammation) with high doses of Busulfan Aspen, at the same time as taking cyclophosphamide as an anticancer or transplant rejection prevention medicine.
• Leukemia

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

• In women, menstruation may stop, fertility may be affected, and early menopause may occur: with usual doses of Busulfan Aspen

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

• A severe decrease in the number of red blood cells in the blood, which can cause fatigue, weakness, bruising, and a higher risk of infection (aplastic anemia)
• Seizures or convulsions: with high doses of Busulfan Aspen
• Cataracts or other eye problems: after a bone marrow transplant and with high doses of Busulfan Aspen
• Feeling unwell (nausea), vomiting, diarrhea, and mouth ulcers: with usual doses of Busulfan Aspen. This can be improved by dividing the dose throughout the day.
• Jaundice (yellowing of the skin or whites of the eyes), liver and bile duct damage: with high doses of Busulfan Aspen
• Dry mouth and lips or any other skin changes, such as darkening of the skin, itching, or skin rash. Hair loss.
• Skin lesions in patients previously treated with radiation therapy
• Abnormal development of certain tissues (dysplasia) that can make it difficult to interpret certain diagnostic tests.

Very rare side effects (may affect up to 1 in 10,000 people)

• Muscle weakness that can cause drooping eyelids, difficulty speaking, or moving arms and legs (myasthenia gravis)
• In men, an increase in breast size
• Symptoms that resemble Addison's disease (weakness, fatigue, weight loss, feeling unwell, and dark spots on the skin) but with the adrenal glands working properly.

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

• Underdeveloped teeth
• An increase in blood pressure in the blood vessels of the lungs (pulmonary hypertension).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines and Healthcare Products Agency (AEMPS) through the website: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Busulfan Aspen

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 after EXP. The expiry date refers to the last day of the month shown.

Do not store above 25°C.

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

6. Contents of the pack and further information

Composition of Busulfan Aspen

• The active substance is busulfan. Each tablet contains 2 mg of busulfan.

• The other ingredients are: anhydrous lactose, pregelatinized corn starch, magnesium stearate, hypromellose, titanium dioxide, and triacetin.

Appearance of the product and pack contents

Busulfan Aspen 2 mg film-coated tablets are white, film-coated, round tablets, engraved with "GX EF3" on one side and "M" on the other.

Busulfan Aspen is available in amber glass bottles with a child-resistant closure, containing 100 tablets.

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

EXCELLA GmbH & Co. KG

Nürnberger Strasse, 12

90537 Feucht

Germany

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

Aspen Pharmacare España S.L.

Avenida Diagonal, 512

Planta Interior 1, Oficina 4

08006 Barcelona

Spain

Date of last revision of this leaflet:June 2025

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