DASATINIB COMBIX 50 mg FILM-COATED TABLETS

Introduction

Package Leaflet:information for the patient

Dasatinib Combix 50 mg film-coated tablets EFG

Dasatinib Combix 70 mg film-coated tablets EFG

Read all of this leaflet carefullybefore you start taking thismedicine,because it contains important informationfor 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 symptoms are the same as yours.
• If you experience 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 Dasatinib Combix and what is it used for
2. What you need to know before you take Dasatinib Combix
3. How to take Dasatinib Combix
4. Possible side effects
5. Storage of Dasatinib Combix
6. Contents of the pack and other information

1. What is Dasatinib Combix and what is it used for

Dasatinib Combix contains the active substance dasatinib. This medicine is used to treat chronic myeloid leukaemia (CML) in adults, adolescents and children from 1 year of age. Leukaemia is a type of cancer that affects the white blood cells. These white blood cells usually help the body fight infections. In patients with CML, a type of white blood cell called granulocytes start to multiply out of control. This medicine inhibits the growth of these leukaemic cells.

Dasatinib Combix is also used to treat Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) in adults, adolescents and children from 1 year of age and lymphoid blast CML in adults who have not benefited from previous treatments. In patients with ALL, a type of white blood cell called lymphocytes multiply too quickly and live too long. This medicine inhibits the growth of these leukaemic cells.

If you have any questions about how Dasatinib Combix works or why you have been prescribed this medicine, ask your doctor.

2. What you need to know before you take Dasatinib Combix

Do not take DasatinibCombix

• if you are allergicto dasatinib or any of the other ingredients of this medicine (listed in section 6).

If you think you may be allergic, talk to your doctor.

Warnings and precautions

Talk to your doctor or pharmacist before you start taking Dasatinib Combix

• if you are taking medicines to thin your bloodor prevent blood clots (see Other medicines and Dasatinib Combix)
• if you have or have had any liver or heart problems
• if you start having difficulty breathing, chest pain or coughwhile taking Dasatinib Combix: this may be a sign of fluid build-up in the lungs or chest (which may be more frequent in patients 65 years or older) or due to changes in the blood vessels that supply blood to the lungs
• if you have ever had or may currently have a hepatitis B virus infection. This is because Dasatinib Combix could cause hepatitis B to become active again, which can be fatal in some cases. Your doctor should carefully check for signs of this infection before starting treatment
• if you experience bruising, bleeding, fever, fatigue and confusion while taking Dasatinib Combix, contact your doctor. This may be a sign of damage to the blood vessels known as thrombotic microangiopathy (TMA).

Your doctor will regularly check your condition to see if Dasatinib Combix is having the desired effect. You will also have regular blood tests while you are taking this medicine.

Children and adolescents

Do not give this medicine to children under 1 year of age. Experience with the use of Dasatinib Combix in this age group is limited. In children taking this medicine, growth and bone development should be closely monitored.

Other medicines and Dasatinib Combix

Tell your doctor or pharmacistif you are taking, have recently taken or might take any other medicines.

Dasatinib Combix is mainly broken down in the liver. Some medicines may interfere with the effect of this medicine when taken together.

The following medicines must not be used during treatment with Dasatinib Combix:

• Ketoconazole, itraconazole – medicines for fungi.
• Erythromycin, clarithromycin, telithromycin – antibiotics.
• Ritonavir – an antiviral medicine.
• Phenytoin, carbamazepine, phenobarbital – treatments for epilepsy.
• Rifampicin – a treatment for tuberculosis.
• Famotidine, omeprazole – medicines that block stomach acid production.
• St John's Wort - a herbal medicine that can be bought without a prescription for the treatment of depressionand other diseases (also known as Hypericum perforatum).

Do not takemedicines that neutralize stomach acid (antacidssuch as aluminium hydroxide/magnesium hydroxide) 2 hours before or 2 hours after taking Dasatinib Combix.

Tell your doctorif you are taking medicines to thin your bloodor prevent blood clots.

Taking Dasatinib Combix with food and drink

Do not take this medicine with grapefruit or grapefruit juice.

Pregnancy and breast-feeding

If you are pregnantor think you may be pregnant or are planning to have a baby, tell your doctor or pharmacist before using this medicine.

Dasatinib Combix must not be used during pregnancyunless clearly necessary. Your doctor will inform you of the potential risk of taking this medicine during pregnancy.

Both men and women are advised to use effective contraceptive methods during treatment with dasatinib.

If you are breast-feeding, tell your doctor.You must stop breast-feeding while taking Dasatinib Combix.

Driving and using machines

Be careful while driving or using machines if you experience side effects such as dizziness or blurred vision.

Dasatinib Combix contains lactose

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

Dasatinib Combix contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; this is essentially “sodium-free”.

3. How to take Dasatinib Combix

This medicine will only be prescribed by a doctor with experience in the treatment of leukaemia. Follow the instructions for administration of this medicine exactly as told by your doctor. If you are unsure, talk to your doctor or pharmacist again. This medicine is prescribed for adults and children from 1 year of age.

The recommended initial dose for adult patients with CML in the chronic phase is 100 mg once a day.

The recommended initial dose for adult patients with CML in the accelerated phase or blast crisis or Ph+ ALL is 140 mg once a day.

Dosing regimen in children with CML in the chronic phase or Ph+ ALL based on body weight.

Dasatinib is given orally once a day as either tablets or powder for oral suspension. Dasatinib tablets are not recommended in patients who weigh less than 10 kg. The powder for oral suspension should be used in patients who weigh less than 10 kg and in patients who cannot swallow the tablets. A dose change may be required when switching between formulations (i.e. tablets and powder for oral suspension), so switching between formulations is not recommended.

Your doctor will decide the correct formulation and dose based on your weight, side effects and response to treatment. In children, the starting dose of this medicine is calculated according to body weight as shown below:

a Dasatinib tablets are not recommended in patients who weigh less than 10 kg, the powder for oral suspension should be used in these patients.

There is no dose recommendation for this medicine in children under 1 year of age.

Depending on how you respond to treatment, your doctor may prescribe a higher or lower dose, or even interrupt treatment briefly. To take higher or lower doses you may need to take combinations of tablets of different strengths.

How to take Dasatinib Combix

Take the tablets at the same time each day.Swallow the tablets whole. Do not crush, cut or chew them.Do not take the tablets dissolved. You cannot be sure you are getting the correct dose if you crush, cut, chew or dissolve the tablets. The tablets of this medicine can be taken with or without food.

Special handling instructions for dasatinib

It is unlikely that dasatinib tablets will break, but if they do break, people other than the patient should wear gloves when handling this medicine.

How long to take this medicine

Take this medicine every day until your doctor tells you to stop.

Make sure you take this medicine for the time your doctor has prescribed.

If you take more Dasatinib Combix than you should

If you accidentally take too many tablets, talk to your doctor immediately. You may need medical attention.

In case of overdose or accidental ingestion, talk to 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 Dasatinib Combix

Do not take a double dose to make up for forgotten doses. Take the next dose at the usual time.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

The following may be signs of serious adverse effects:

• If you have chest pain, difficulty breathing, coughing, and fainting.
• If you have an unexpected bleedingor bruising without injury.
• If you notice blood in your vomit, stool, or urine, or if you have black stools.
• If you develop infection symptoms, such as fever, intense chills.
• If you have a fever, mouth or throat pain, itching, or skin peeling and/or mucous membranes.

Contact your doctor immediatelyif you notice any of the above.

Very common adverse effects (may affect more than 1 in 10 patients)

• Infections(caused by bacteria, viruses, and fungi).
• Heart and lungs: difficulty breathing.
• Digestive problems: diarrhea, feeling unwell (nausea, vomiting).
• Skin, hair, eyes, general: skin rash, fever, swelling in the face, hands, and feet, headache, fatigue or weakness, bleeding.
• Pain: muscle pain (during or after stopping treatment), abdominal pain.
• Laboratory tests: low platelet count, low white blood cell count (neutropenia), anemia, fluid around the lungs.

Common adverse effects (may affect up to 1 in 10 patients)

• Infections: pneumonia, herpes virus infection (including cytomegalovirus - CMV), upper respiratory tract infection, severe blood or tissue infection (including rare cases with fatal outcomes).
• Heart and lungs: palpitations, irregular heartbeat, congestive heart failure, weak heart muscle, high blood pressure, high blood pressure in the lungs, cough.
• Digestive problems: changes in appetite, changes in taste, abdominal distension or swelling, colon inflammation, constipation, gastroesophageal reflux, oral ulcers, weight loss, weight gain, gastritis.
• Skin, hair, eyes, general: tingling sensation on the skin, itching, dry skin, acne, skin inflammation, persistent ringing in the ears, hair loss, excessive sweating, vision disorders (including blurred vision and distorted vision), dry eyes, bruising, depression, insomnia, hot flashes, dizziness, bruising, anorexia, drowsiness, generalized edema.
• Pain: joint pain, muscle weakness, chest pain, pain in the hands and feet, chills, muscle and joint stiffness, muscle spasms.
• Laboratory tests: fluid around the heart, fluid in the lungs, heart arrhythmias, febrile neutropenia, gastrointestinal bleeding, high levels of uric acid in the blood.

Uncommon adverse effects (may affect up to 1 in 100 patients)

• Heart and lungs: heart attack (including fatal outcome), inflammation of the membrane surrounding the heart (pericarditis), irregular heartbeat, chest pain due to lack of blood supply to the heart (angina), low blood pressure, narrowing of the airways that could cause breathing difficulties, asthma, high blood pressure in the arteries (blood vessels) that go to the lungs.
• Digestive problems: pancreatitis, peptic ulcer, inflammation of the digestive tract, abdominal swelling, anal fissure, difficulty swallowing, gallbladder inflammation, bile duct obstruction, gastroesophageal reflux (stomach acid and other contents return to the throat).
• Skin, hair, eyes, general: allergic reactions including sensitivity, red lumps on the skin (erythema nodosum), anxiety, confusion, mood swings, low sex drive, fainting, tremors, eye inflammation that can cause redness or pain, skin disease characterized by sensitivity, redness, and well-defined spots with sudden onset of fever and elevated white blood cell count (neutrophilic dermatosis), hearing loss, sensitivity to light, visual disturbances, increased tearing, changes in skin pigmentation, inflammation of the fatty tissue under the skin, skin ulcers, blisters on the skin, changes in nails, changes in hair, changes in hands and feet, kidney failure, frequent urination, breast enlargement in men, changes in menstruation, general weakness and malaise, low thyroid function, loss of balance while walking, osteonecrosis (a disease where blood supply to the bones is reduced, which can cause bone loss and death), arthritis, skin swelling anywhere on the body.
• Pain: inflammation of the veins that can cause redness, sensitivity, and swelling, tendon inflammation.
• Brain: memory loss.
• Additional tests: abnormal blood test results and possibly kidney failure caused by tumor waste products during healing (tumor lysis syndrome), low albumin levels in the blood, low lymphocyte levels in the blood, high cholesterol levels in the blood, swelling of the lymph nodes, cerebral hemorrhage, irregular heart activity, enlarged heart, liver inflammation, protein in the urine, elevated creatine phosphokinase (an enzyme found mainly in the heart, brain, and skeletal muscles), elevated troponin (an enzyme found mainly in the heart and skeletal muscle), elevated gamma-glutamyl transferase (an enzyme found mainly in the liver), milky fluid around the lungs (chylothorax).

Rare adverse effects (may affect up to 1 in 1000 patients)

• Heart and lungs: dilation of the right ventricle of the heart, inflammation of the heart muscle, set of symptoms produced by the blockage of blood supply to the heart muscle (acute coronary syndrome), heart attack (interruption of blood supply to the heart), coronary artery disease (of the heart), inflammation of the tissue that covers the heart and lungs, blood clots, blood clots in the lungs.
• Digestive problems: loss of essential nutrients such as proteins from the digestive system, intestinal obstruction, anal fistula (abnormal opening of the anus to the surrounding skin), kidney failure, diabetes.
• Skin, hair, eyes, general: seizures, inflammation of the optic nerve that can cause complete or partial vision loss, bluish-purple spots on the skin, abnormally high thyroid function, thyroid gland inflammation, ataxia (associated with loss of muscle coordination), difficulty walking, spontaneous abortion, skin inflammation of blood vessels, cutaneous fibrosis.
• Brain: stroke, temporary episode of neurological failure caused by loss of blood flow, facial nerve paralysis, dementia.
• Immune system: severe allergic reactions.
• Connective tissue and musculoskeletal system: delayed fusion of the rounded ends that form joints (epiphysis); slow or delayed growth.

Other adverse effects that have been reported with unknown frequency (frequency cannot be estimated from available data)

• Lung inflammation.
• Bleeding in the stomach or intestine that can cause death.
• Recurrence (reactivation) of hepatitis B virus infection if you have had hepatitis B in the past (a liver infection).
• Reaction with fever, blisters on the skin, and mucous membrane ulcers.
• Kidney disorders with symptoms such as edema and abnormal laboratory test results such as protein in the urine and low protein levels in the blood.
• Damaged blood vessels known as thrombotic microangiopathy (TMA), which includes decreased red blood cell count, decreased platelet count, and blood clot formation.

Your doctor will check if you have any of these effects during your treatment.

Reporting adverse effects

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

5. Storage of Dasatinib Combix

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date shown on the blister pack and carton after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE collection point in your pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Dasatinib Combix

• The active ingredient is dasatinib. Each film-coated tablet contains 50 mg or 70 mg of dasatinib (as monohydrate).
• The other ingredients (excipients) are:

Tablet core: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, hydroxypropylcellulose, magnesium stearate, and colloidal silicon dioxide.

Tablet coating: coating agent (composed of poly(vinyl alcohol), talc, titanium dioxide (E171), glycerol, and sodium lauryl sulfate).

Appearance of the product and package contents

Dasatinib Combix 50 mg: the film-coated tablets are white to off-white, oval, approximately 10.9 x 5.9 mm in size, with "1742" engraved on one side and smooth on the other.

Dasatinib Combix 70 mg: the film-coated tablets are white to off-white, round, approximately 9.2 mm in diameter, with "1743" engraved on one side and smooth on the other.

Dasatinib Combix 50 mg or 70 mg film-coated tablets are available in packages containing 56 or 60 film-coated tablets in precut blisters.

Marketing authorization holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus FranceZAC Les Hautes PaturesParc d'activités des Peupliers25 Rue des Peupliers92000 NanterreFrance

or

Centre Specialites Pharmaceutiques

Z.A.C. des Suzots

35 Rue de la Chapelle

63450 Saint Amant Tallende

France

or

Netpharmalab Consulting Services

Carretera de Fuencarral 22,

Alcobendas,

28108 Madrid

Spain

or

Flavine Pharma France

3 Voie d’Allemagne

13127 Vitrolles

France

Date of the last revision of this leaflet: June 2025

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