DARUPH 111 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Daruph 40 mg film-coated tablets

Daruph 55 mg film-coated tablets

Daruph 79 mg film-coated tablets

Daruph 111 mg film-coated tablets

dasatinib

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

1. What is Daruph and what is it used for

Daruph is a medicine that 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 of the white blood cells. These white blood cells usually help the body to fight infections. In patients with CML, a type of white blood cell called granulocytes start to multiply out of control. Daruph inhibits the growth of these leukaemic cells.

Daruph 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 crisis CML in adults who have not benefited from previous treatments. In patients with Ph+ ALL, a type of white blood cell called lymphocytes multiply too quickly and live too long. Daruph inhibits the growth of these leukaemic cells.

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

2. What you need to know before you take Daruph

Do not takeDaruph

if you are allergic to 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 taking Daruph if:

• you are taking medicines to make your blood thinner or prevent blood clots (see "Other medicines and Daruph").
• you have or have had any liver or heart problems.
• you start to have difficulty breathing, chest pain, or cough while taking Daruph: this may be a sign of fluid build-up in the lungs or chest (which can be more frequent in patients 65 years or older) or due to changes in the blood vessels that supply blood to the lungs.
• you have ever had or may currently have a hepatitis B virus infection. This is because dasatinib could cause hepatitis B to become active again, which can be fatal in some cases. Your doctor will carefully check for signs of this infection before starting treatment.
• you experience bruising, bleeding, fever, fatigue, and confusion while taking Daruph, contact your doctor. This may be a sign of damage to the blood vessels known as thrombotic microangiopathy (TMA).
• your doctor has told you that you have a decrease in stomach acidity (achlorhydria/hypochlorhydria). The dose of Daruph may need to be adjusted.

Your doctor will regularly check your condition to see if Daruph is having the desired effect. You will also have regular blood tests while taking Daruph.

Children and adolescents

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

Other medicines and Daruph

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

Dasatinib is mainly broken down by the liver. Some medicines may interfere with the effect of Daruph when taken together.

The following medicines must not be used during treatment with Daruph:

• Ketoconazole, itraconazole - antifungal medicines.
• Erythromycin, clarithromycin, telithromycin - antibiotics.
• Ritonavir - antiviral medicine.
• Phenytoin, carbamazepine, phenobarbital - treatments for epilepsy.
• Rifampicin - treatment for tuberculosis.
• St. John's Wort - a herbal medicine that can be bought without a prescription for the treatment of depression and other conditions (also known as Hypericum perforatum).

Do not take medicines that neutralize stomach acid (antacids such as aluminium hydroxide/magnesium hydroxide) in the 2 hours before or 2 hours after taking Daruph.

If you use medicines that block stomach acid such as omeprazole, to get the best results, this medicine should be taken 2 hours after taking Daruph.

Tell your doctor if you are taking medicines to make your blood thinner or prevent blood clots.

TakingDaruphwith food and drinks

Do not take Daruph with grapefruit or grapefruit juice.

Pregnancy and breast-feeding

If you are pregnant or think you may be pregnant, tell your doctor immediately. Daruph should not be used during pregnancy unless clearly necessary. Your doctor will inform you of the potential risk of taking Daruph during pregnancy.

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

If you are breast-feeding, tell your doctor. You should interrupt breast-feeding while taking Daruph.

Driving and using machines

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

Daruphcontains lactose and sodium

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

This medicine contains less than 1 mmol of sodium (23 mg) per tablet, which is essentially "sodium-free".

3. How to take Daruph

Do not change taking Daruph tablets for other dasatinib tablets without consulting your doctor. The concentration of Daruph tablets is different from that of other medicines containing dasatinib.

Dasatinib will only be prescribed by a doctor with experience in the treatment of leukaemia. Follow exactly the administration instructions of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again. Daruph 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 79 mg once daily.

The recommended initial dose for adult patients with CML in the accelerated phase or blast crisis or Ph+ ALL is 111 mg once daily.

The administration schedule in children with CML in the chronic phase or Ph+ ALL is based on body weight.

Dasatinib is given orally once daily, either as film-coated tablets or as a powder for oral suspension. Daruph film-coated 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 change in dose may be required when changing between formulations (i.e., tablets and powder for oral suspension), so do not change from one formulation to another. Your doctor will decide on the correct formulation and dose based on your weight, side effects, and response to treatment. In children, the starting dose of Daruph is calculated based on body weight as shown below:

There is no recommended dose for Daruph 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 takeDaruph

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. Daruph tablets can be taken with or without food.

Special handling instructions for Daruph

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

How long to take Daruph

Take Daruph daily until your doctor tells you to stop. Make sure you take Daruph for the duration your doctor has prescribed.

If you take moreDaruphthan 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, contact 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 takeDaruph

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

If you have any other questions about 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 unexpected bleeding or bruising without injury.
• If you notice blood in your vomit, stools, or urine, or if you have black stools.
• If you develop symptoms of infection, such as fever, intense chills.
• If you have fever, pain in the mouth or throat, itching, or peeling of the skin and/or mucous membranes.

Contact your doctor immediatelyif you notice any of the above.

Adverse effects very frequently(may affect more than 1 in 10 people):

• Infections (including bacteria, viruses, and fungi).
• Heart and lungs: difficulty breathing.
• Digestive problems: diarrhea, feeling unwell (nausea, vomiting).
• Skin, hair, eyes, general: rash, fever, swelling of 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.

Adverse effects frequently(may affect up to 1 in 10 people):

• 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, coughing.
• Digestive problems: changes in appetite, changes in taste, abdominal distension or swelling, colon inflammation, constipation, esophageal 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, visual disturbances (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, deficiency in all blood cells, gastrointestinal bleeding, high levels of uric acid in the blood.

Adverse effects infrequently(may affect up to 1 in 100 people):

• Heart and lungs: heart attack (including fatal outcome), inflammation of the membrane surrounding the heart (fibrous sac), 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: pancreas inflammation, peptic ulcer, digestive tract inflammation, abdominal swelling, tear in the skin of the anal canal, 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, well-defined spots with sudden onset of fever and elevated white blood cell count (neutrophilic dermatosis), hearing loss, sensitivity to light, visual disturbances, increased eye tearing, changes in skin color, 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 discomfort, 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 blood, low lymphocyte levels in blood, high cholesterol levels in blood, swelling of lymph nodes, cerebral hemorrhage, irregularity of heart electrical activity, enlarged heart, liver inflammation, protein in urine, elevated creatine phosphokinase (an enzyme found mainly in the heart, brain, and skeletal muscles), increased troponin (an enzyme found mainly in the heart and skeletal muscle), increased gamma-glutamyl transferase (an enzyme found mainly in the liver), milky fluid around the lungs (chylothorax).

Adverse effects rarely(may affect up to 1 in 1,000 people):

• Heart and lungs: dilation of the right ventricle of the heart, heart muscle inflammation, 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 vital 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, inflammation of the skin of blood vessels, skin 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(cannot be estimated from the 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.
• Damage to 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 of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is an 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 Daruph

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

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

6. Package Contents and Additional Information

Composition ofDaruph

• The active ingredient is dasatinib. Each film-coated tablet contains 39.5 mg, 55.3 mg, 79 mg, or 110.6 mg of dasatinib.
• The other ingredients are:

Core of the tablet: lactose monohydrate, microcrystalline cellulose, hydroxypropylcellulose, sodium croscarmellose, magnesium stearate.

Coating: hypromellose, propylene glycol, titanium dioxide, yellow iron oxide (E 172) (only for Daruph 55 mg film-coated tablets).

Appearance of the Product and Package Contents

Daruph 40 mg film-coated tablets

White to off-white, round, film-coated tablets with a diameter of 7 mm, engraved on one side with "39.5".

Daruph 55 mg film-coated tablets

Light yellow to yellow, round, film-coated tablets with a diameter of 7 mm, engraved on one side with "55.3".

Daruph 79 mg film-coated tablets

White to off-white, round, film-coated tablets with a diameter of 9.5 mm, engraved on one side with "79.0".

Daruph 111 mg film-coated tablets

White to off-white, round, film-coated tablets with a diameter of 11 mm, engraved on one side with "110.6".

Daruph is packaged in OPA/Alu/PVC//Alu blisters.

Package sizes: Daruph 40 mg, 55 mg film-coated tablets: 56 and 60 film-coated tablets. Daruph 79 mg, 111 mg film-coated tablets: 28 and 30 film-coated tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder

Zentiva, k.s.

U Kabelovny 130,

Dolní Mecholupy,

102 37 Prague 10,

Czech Republic

Manufacturer

Zentiva, k.s.

U Kabelovny 130

102 37 Prague 10

Czech Republic

or

Pharmacare Premium Ltd.

HHF003 Hal Far Industrial Estate,

Hal Far Birzebbugia

BBG 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 Area with the following names:

Germany, Slovakia, Spain, Hungary, Italy, Poland, Czech Republic, Romania, Sweden: Daruph

Date of the last revision of this leaflet: February 2024

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/