Dasatinib zentiva

Package leaflet: Information for the user

Dasatinib Zentiva, 20 mg, film-coated tablets
Dasatinib Zentiva, 50 mg, film-coated tablets
Dasatinib Zentiva, 80 mg, film-coated tablets
Dasatinib Zentiva, 100 mg, film-coated tablets
Dasatinib Zentiva, 140 mg, film-coated tablets
dazatynib
Please read this leaflet carefully before 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, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

1. What Dasatinib Zentiva is and what it is used for
2. Important information before taking Dasatinib Zentiva
3. How to take Dasatinib Zentiva
4. Possible side effects
5. How to store Dasatinib Zentiva
6. Contents of the pack and other information

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

Dasatinib Zentiva contains the active substance dasatinib. This medicine is used to treat chronic
myeloid leukaemia (CML) in adults, adolescents and children aged at least 1 year. Leukaemia
is a cancer of the white blood cells. Normally, white blood cells help the body fight infections.
In people with CML, white blood cells called granulocytes grow uncontrollably. Dasatinib Zentiva
inhibits the growth of these leukaemic cells.
Dasatinib Zentiva is also used to treat acute lymphoblastic leukaemia (ALL) with the Philadelphia
chromosome (Ph+) in adults, adolescents and children aged at least 1 year, as well as for the
lymphoblastic blast crisis phase of CML in adults who have not responded to prior therapy.
In people with acute lymphoblastic leukaemia, white blood cells called lymphocytes multiply too
quickly and live too long. Dasatinib Zentiva inhibits the growth of these leukaemic cells.
If you have any questions about how Dasatinib Zentiva works or why this medicine has been
prescribed, please consult your doctor.

2. Important information before taking Dasatinib Zentiva

When not to take Dasatinib Zentiva

• if the patient is allergic to dasatinib or any of the other ingredients of this medicine (listed in section 6). Consult a doctor if an allergic reaction is suspected.

Warnings and precautions
Before starting Dasatinib Zentiva, discuss this with your doctor or pharmacist.

• if you are taking anticoagulant medicines or medicines that prevent blood clots (see section "Dasatinib Zentiva and other medicines"),
• if you have previously or currently have liver or heart function disorders,
• if you experience difficulty breathing, chest pain, or cough while taking Dasatinib Zentiva: these may be symptoms of fluid accumulation in the lungs or chest cavity (which may occur more frequently in patients aged 65 years and older) or caused by changes in blood vessels supplying blood to the lungs,
• if you have ever had or may currently have hepatitis B virus infection; this is because dasatinib may reactivate hepatitis B virus, which in some cases may lead to death. Patients will be closely monitored by the doctor for signs of this infection before starting treatment,
• if you develop bruising, bleeding, fever, fatigue, or confusion while taking Dasatinib Zentiva, contact your doctor immediately. These may indicate damage to blood vessels known as thrombotic microangiopathy (TMA).

Your treating doctor will carry out periodic checks during treatment to assess whether Dasatinib Zentiva is having the intended effect. Regular blood tests will also be performed while taking Dasatinib Zentiva.

Children and adolescents
Do not use this medicine in children under one year of age. Data on the use of dasatinib in this age group are limited. Growth and bone development should be carefully monitored in children taking Dasatinib Zentiva.

Dasatinib Zentiva and other medicines
Inform your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.

Dasatinib is mainly metabolized in the liver. Certain medicines may affect the action of Dasatinib Zentiva when used concomitantly.

Do not take the following medicines with Dasatinib Zentiva:

• ketoconazole, itraconazole – antifungal medicines
• erythromycin, clarithromycin, telithromycin – antibiotics
• ritonavir – an antiviral medicine
• phenytoin, carbamazepine, phenobarbital – medicines used for epilepsy
• rifampicin – a medicine used for tuberculosis
• famotidine, omeprazole – medicines that reduce stomach acid secretion
• St. John's wort – a herbal remedy available without prescription, used in the treatment of depression and other conditions (also known as Hypericum perforatum)

Do not take medicines that neutralize stomach acid (such as aluminium hydroxide or magnesium hydroxide) within 2 hours before or 2 hours after taking Dasatinib Zentiva.
Inform your doctor if you are taking medicines that thin the blood or prevent blood clots.

Taking Dasatinib Zentiva with food and drink
Do not take Dasatinib Zentiva with grapefruit or grapefruit juice.

Pregnancy and breastfeeding
Women who are pregnant or suspect they may be pregnant should inform their doctor. Dasatinib Zentiva should not be given to pregnant women unless absolutely necessary. Your doctor will explain the potential risks associated with taking Dasatinib Zentiva during pregnancy.

It is recommended that both men and women use effective contraception during treatment with Dasatinib Zentiva.

Inform your doctor if you are breastfeeding. Breastfeeding is not recommended while taking Dasatinib Zentiva.

Driving and operating machinery
Exercise particular caution when driving or operating machinery if you experience adverse effects such as dizziness or visual disturbances.

Dasatinib Zentiva contains lactose and sodium
If you have previously been diagnosed with intolerance to certain sugars, inform your doctor before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; therefore, this medicine is considered "sodium-free".

3. How to take Dasatinib Zentiva

Dasatinib Zentiva will be prescribed only by a physician experienced in the treatment of leukemia. This medicine must always be taken exactly as directed by the physician. In case of any doubts, consult your physician or pharmacist. Dasatinib Zentiva is intended for adults and children aged at least 1 year.

The recommended initial dose for adult patients in the chronic phase of CML is 100 mg taken orally once daily.

The recommended initial dose for adult patients in the accelerated phase or blast phase of CML, or with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), is 140 mg taken orally once daily.

Dosing in children with chronic phase CML or Ph+ ALL is based on body weight. Dasatinib is administered orally once daily either as tablets or as oral suspension powder. The use of tablets is not recommended in patients with body weight less than 10 kg.

In patients with body weight less than 10 kg and in patients unable to swallow tablets, the oral suspension powder should be used. When switching between formulations (i.e., tablets and oral suspension powder), a dose adjustment may be required. In such cases, do not switch from one formulation to another without medical advice.

Based on the patient's body weight, adverse reactions, and response to treatment, the physician will determine the appropriate formulation and dose. The initial dose of Dasatinib Zentiva in children, adjusted according to body weight, is as follows:

| Body weight (kg) | Daily dose (mg) | |------------------|-----------------| | 10 to less than 20 kg | 40 mg | | 20 to less than 30 kg | 60 mg | | 30 to less than 45 kg | 70 mg | | at least 45 kg | 100 mg |

a Tablets are not recommended in patients with body weight less than 10 kg; in such patients, the oral suspension powder should be used.

There are no dosage recommendations for Dasatinib Zentiva in children under 1 year of age.

Depending on the response to treatment, the physician may decide to increase or decrease the dose, or temporarily interrupt treatment. To achieve higher or lower doses, it may be necessary to use a combination of tablets with different strengths.

How to take Dasatinib Zentiva

Tablets should be taken at the same time each day. Tablets must be swallowed whole. Do not crush, split, or chew them. Do not take crushed tablets.

If tablets are crushed, cut, chewed, or otherwise damaged, there is no guarantee that the patient will receive the correct dose. Dasatinib Zentiva tablets may be taken with or without food.

Special handling instructions for Dasatinib Zentiva

It is unlikely that Dasatinib Zentiva tablets will be damaged. However, in such a case, individuals handling Dasatinib Zentiva should wear protective gloves.

How long to take Dasatinib Zentiva

Dasatinib Zentiva should be taken every day until the physician decides to discontinue treatment. Ensure that Dasatinib Zentiva is taken for as long as prescribed by the physician.

Taking more than the recommended dose of Dasatinib Zentiva

If a patient accidentally takes more tablets than prescribed, contact the physician immediately, as medical attention may be required.

Missed dose of Dasatinib Zentiva

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

If you have any further questions about the use of this medicine, consult your physician or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.
All of the symptoms listed below may indicate serious adverse reactions:

• if chest pain, difficulty breathing, cough and fainting occur

• if unexpected bleeding or bruising occurs without prior injury

• if blood is present in vomit, stool or urine, or if the stool is black in colour

• if signs of infection appear, such as fever, severe chills

• if fever, mouth or throat pain, formation of blisters or peeling of the skin and (or) mucous membranes occur. You should inform your doctor immediately if any of the symptoms listed above occur.

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

• Infections (including bacterial, viral and fungal infections)
• Heart and lungs: shortness of breath
• Gastrointestinal disorders: diarrhoea, nausea or vomiting
• Skin, hair, eyes, general symptoms: skin rash, fever, swelling of the face, hands and feet, headache, feeling tired or weak, bleeding
• Pain: muscle pain (during treatment or after discontinuation), abdominal pain
• Laboratory tests may show: low platelet count, low white blood cell count (neutropenia), anaemia, presence of fluid around the lungs.

Common adverse reactions (may affect up to 1 in 10 people):

• Infections: pneumonia, herpes virus infection (including cytomegalovirus - CMV), upper respiratory tract infections, severe blood or tissue infection (including uncommon cases resulting in death)
• Heart and lungs: palpitations, irregular heartbeat, congestive heart failure, weakening of the heart muscle, high blood pressure, increased blood pressure in the lungs, cough
• Gastrointestinal disorders: appetite disturbances, taste disturbances, bloated or enlarged abdomen, inflammation of the large intestine, constipation, heartburn, mouth ulcers, weight gain, weight loss, stomach inflammation
• Skin, hair, eyes, general symptoms: tingling, skin itching, dry skin, acne, skin inflammation, persistent ringing in the ears, hair loss, excessive sweating, vision disturbances (including blurred and disturbed vision), dry eyes, bruising, depression, insomnia, sudden skin redness, dizziness, injuries (bruises), loss of appetite, drowsiness, generalised swelling
• Pain: joint pain, muscle weakness, chest pain, pain in hands and feet, chills, muscle and joint stiffness, muscle cramps
• Laboratory tests may show: presence of fluid around the heart, presence of fluid in the lungs, heart rhythm disturbances, decreased white blood cell count (neutropia) with fever, gastrointestinal bleeding, high levels of uric acid in the blood.

Uncommon adverse reactions (may affect up to 1 in 100 people):

• Heart and lungs: heart attack (including fatal cases), inflammation of the lining (fibrous sac) around the heart, irregular heartbeat, chest pain due to lack of blood flow to the heart (angina pectoris), low blood pressure, narrowing of the airways which may cause breathing difficulties, asthma, increased blood pressure in the pulmonary arteries (blood vessels of the lungs)
• Gastrointestinal disorders: pancreatitis, peptic ulcer disease, oesophagitis, abdominal swelling (ascites), anal fissure, difficulty swallowing, gallbladder inflammation, biliary tract obstruction, gastro-oesophageal reflux (a condition in which acid and other stomach contents flow back into the throat)
• Skin, hair, eyes, general symptoms: allergic reactions, including formation of tender red nodules on the skin (erythema nodosum), anxiety, disorientation, mood changes, decreased libido, fainting, tremor, eye inflammation causing redness or pain, skin disease characterised by tender, red, well-defined erythematous patches on the skin with sudden onset of fever and increased white blood cell count (neutrophilic dermatosis), hearing loss, light sensitivity, vision disturbance, excessive eye tearing, skin pigmentation disorders, inflammation of subcutaneous fat tissue, skin ulceration, blistering of the

skin, nail disorders, hair disorders, disorders of the
hands and feet, kidney failure, frequent urination, breast enlargement in
men, menstrual disorders, general weakness and discomfort, decreased
thyroid function, loss of balance while walking, bone necrosis (a condition
characterised by reduced blood flow in the bones, leading to loss of bone mass and
bone death), joint inflammation, skin swelling in any part of the body

• Pain: vein inflammation, which may cause redness, pain and swelling, tendon inflammation
• Brain: memory loss
• Laboratory tests may show: abnormal blood test results and possible kidney function disorders caused by tumour lysis products (tumour lysis syndrome), low blood albumin levels, low lymphocyte count (a type of white blood cell) in the blood, high cholesterol levels in the blood, swollen lymph nodes, brain haemorrhage, abnormalities in the electrical activity of the heart, heart enlargement, liver inflammation, presence of protein in the urine, increased creatine kinase activity (an enzyme mainly present in the heart, brain and skeletal muscles), increased troponin activity (an enzyme mainly present in the heart and skeletal muscles), increased gamma-glutamyl transferase activity (an enzyme mainly present in the liver), milky-appearing fluid around the lungs (chylothorax).

Rare adverse reactions (may affect up to 1 in 1000 people):

• Heart and lungs: enlargement of the right ventricle of the heart, myocarditis (inflammation of the heart muscle), syndrome of symptoms resulting from blocked blood flow to the heart muscle (acute coronary syndrome), cardiac arrest (cessation of blood ejection from the heart), coronary artery disease (heart), inflammation of the tissue covering the heart and lungs, blood clots, blood clots in the lungs
• Gastrointestinal disorders: loss of essential nutrients from the gastrointestinal tract such as proteins, intestinal obstruction, fistula of the anus (abnormal formation of a channel between the anus and the skin around the anus), kidney function disorder, diabetes
• Skin, hair, eyes, general symptoms: seizures, optic neuritis which may cause complete or partial vision loss, blue-violet skin spots, hyperthyroidism, thyroid gland inflammation, ataxia (a condition associated with lack of muscular coordination), difficulty walking, miscarriage, skin vasculitis, skin fibrosis
• Brain: stroke, transient occurrence of neurological disturbances caused by lack of blood flow, facial nerve paralysis, dementia
• Immune system: severe allergic reaction
• Musculoskeletal and connective tissue: delayed healing of rounded ends of bones (epiphyses) forming joints; slowed or delayed growth.

Other observed adverse reactions with unknown frequency (frequency cannot be estimated from the available data):

• Pneumonitis
• Bleeding in the stomach or intestines, which may lead to death
• Reactivation of hepatitis B virus infection in patients who have previously had this disease
• Reaction with fever, blistering of the skin and ulceration of mucous membranes
• Kidney disease with symptoms including oedema and abnormal laboratory test results such as protein in the urine and low blood protein levels
• Damage to blood vessels known as thrombotic microangiopathy (TMA), including reduced number of red blood cells, reduced platelet count and blood clot formation. During treatment, your doctor will check for the occurrence of these adverse reactions.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, you should inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder or representative of the marketing authorisation holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Dasatinib Zentiva

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label of the bottle, blister pack,
or carton after the word "EXP". The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines must 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 other information

What Dasatinib Zentiva contains

• The active substance is dasatinib. Each film-coated tablet contains 20 mg, 50 mg, 80 mg, 100 mg, or 140 mg of dasatinib.
• The other ingredients are:
• Tablet core: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, hydroxypropylcellulose, magnesium stearate
• Tablet coating: lactose monohydrate, hypromellose, titanium dioxide (E171), triacetin (see section 2 “Dasatinib Zentiva contains lactose and sodium”)

What Dasatinib Zentiva looks like and contents of the pack
Dasatinib Zentiva 20 mg: The film-coated tablet is white or almost white, biconvex, round, approximately 5.6 mm in diameter, with the imprint “D7SB” on one side and “20” on the other side.
Dasatinib Zentiva 50 mg: The film-coated tablet is white or almost white, biconvex, oval, approximately 6.0 mm in diameter, with the imprint “D7SB” on one side and “50” on the other side.
Dasatinib Zentiva 80 mg: The film-coated tablet is white or almost white, biconvex, triangular, approximately 10.4 mm in length, with the imprint “D7SB” on one side and “80” on the other side.
Dasatinib Zentiva 100 mg: The film-coated tablet is white or almost white, biconvex, oval, approximately 15.1 mm in length and 7.1 mm in width, with the imprint “D7SB” on one side and “100” on the other side.
Dasatinib Zentiva 140 mg: The film-coated tablet is white or almost white, biconvex, round, approximately 11.7 mm in length, with the imprint “D7SB” on one side and “140” on the other side.
Dasatinib Zentiva 20 mg and 50 mg are available in cardboard boxes containing:
60 film-coated tablets in blisters or 60 x 1 film-coated tablet in unit dose blisters.
They are also available in cardboard boxes containing bottles with 60 film-coated tablets.
Dasatinib Zentiva 80 mg, 100 mg or 140 mg are available in cardboard boxes containing:
30 film-coated tablets in blisters or 30 x 1 film-coated tablet in unit dose blisters.
They are also available in cardboard boxes containing bottles with 30 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva k.s., U kabelovny 130, Dolní Měcholupy, 102 37 Prague 10, Czech Republic.

Manufacturer:
Synthon Hispania, S.L., Calle Castello 1, Poligono Las Salinas
Sant Boi De Llobregat
08830 Barcelona, Spain
Synthon B.V.
Microweg 22
6545 CM Nijmegen
The Netherlands

This medicinal product is authorised for marketing in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Bulgaria, Estonia, Croatia, Denmark, France, The Netherlands, Lithuania, Latvia, Poland, Portugal, Czech Republic, Slovak Republic, Romania, Sweden, Hungary, United Kingdom (Northern Ireland), Italy: Dasatinib Zentiva