Imatinib Zentiva

Leaflet accompanying the packaging: patient information

Imatinib Zentiva, 100 mg, film-coated tablets

Imatinib Zentiva, 400 mg, film-coated tablets

Imatinib

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed to a specific person. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

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

Imatinib Zentiva is a medicine that contains the active substance imatinib. This medicine works by inhibiting the growth of abnormal cells in the course of the diseases listed below. These include certain types of cancer.

Imatinib Zentiva is used to treat adult patients and children with:

• Chronic myeloid leukemia (CML)- English: Chronic Myeloid Leukaemia). Leukemia is a cancer of white blood cells. Normally, white blood cells help the body fight infections. Chronic myeloid leukemia is a type of leukemia in which certain abnormal white blood cells (called myeloid cells) begin to multiply uncontrollably. In adult patients, Imatinib Zentiva is used to treat the late phase of CML called "blast crisis". In children and adolescents, it may be used to treat all stages of the disease.
• Acute lymphoblastic leukemia with Philadelphia chromosome (English: Ph-positive ALL). Leukemia is a cancer that originates from white blood cells. Normally, white blood cells help the body fight infections. Acute lymphoblastic leukemia is a type of leukemia in which certain abnormal white blood cells (called lymphoblasts) begin to multiply uncontrollably. Imatinib Zentiva inhibits the growth of these cells.

Imatinib Zentiva is also indicated for the treatment of adult patients with:

Myelodysplastic/myeloproliferative syndromes MDS/MPD- English: myelodysplastic/myeloproliferate). These are blood diseases in which certain white blood cells begin to multiply uncontrollably. Imatinib Zentiva inhibits the growth of these cells in certain subtypes of these diseases.

• Hypereosinophilic syndrome HES- English: Hypereosinophilic Syndrome) and (or) chronic eosinophilic leukemia CEL- English: Chronic Eosinophilic Leukemia). These are blood diseases in which certain blood cells (called eosinophils) begin to multiply uncontrollably. Imatinib inhibits the growth of these cells in certain subtypes of these diseases.
• Gastrointestinal stromal tumors (GIST- English: Gastrointestinal Stromal Tumours). GIST is a stomach and intestine cancer. It arises from the uncontrolled growth of connective tissue cells of these organs.
• Dermatofibrosarcoma protuberans DFSP- English: dermatofibrosarcoma protuberans). DFSP is a skin and subcutaneous tissue cancer in which certain cells begin to multiply uncontrollably. Imatinib Zentiva inhibits the growth of these cells.

In the rest of the leaflet, abbreviations of the disease names mentioned above will be used.
In case of any questions about the mechanism of action or justification of the use of Imatinib Zentiva, you should consult a doctor.

2. Important information before taking Imatinib Zentiva

Imatinib Zentiva will be prescribed to patients only by doctors with experience in using medicines for the treatment of blood cancers or solid tumors.
It is essential to strictly follow the doctor's recommendations, even if they differ from the general information contained in this leaflet.

When not to take Imatinib Zentiva:

• if the patient is allergic to imatinib or any of the other ingredients of this medicine (listed in section 6). If this information applies to the patient, they should tell their doctor before taking the medicine

Imatinib Zentiva.

In case of suspected allergy, but uncertainty, the patient should consult a doctor.

Warnings and precautions

Before starting treatment with Imatinib Zentiva, the patient should consult a doctor:

• if the patient has or has had liver, kidney, or heart disease.
• if the patient is taking levothyroxine after thyroid removal.
• if the patient has or may have a hepatitis B virus infection; this is because Imatinib Zentiva may cause reactivation of hepatitis B virus infection, which can be fatal in some cases; patients will be closely monitored by the doctor for signs of this infection before starting treatment.
• if the patient experiences bruising, bleeding, fever, fatigue, and disorientation while taking Imatinib Zentiva, they should contact their doctor. This may be a sign of blood vessel damage called thrombotic microangiopathy (TMA).

If any of the above points apply to the patient, they should tell their doctor before taking Imatinib Zentiva.
While taking Imatinib Zentiva, the patient may become more sensitive to the sun. It is essential to cover sun-exposed skin areas and use sunscreens with a high sun protection factor (SPF). These precautions should also be taken by children.
The patient should immediately tell their doctor if they experience
rapid weight gain during treatment with Imatinib Zentiva.Imatinib Zentiva may cause water retention in the body (severe fluid retention).
While taking Imatinib Zentiva, the doctor will regularly assess whether the treatment with Imatinib Zentiva is effective. The patient will also have regular blood tests and weight measurements.

Children and adolescents

Imatinib Zentiva is also used to treat children with CML. There is limited experience with the use of Imatinib Zentiva in children with CML under the age of 2. Experience with the use of Imatinib Zentiva in children with Ph-positive ALL is limited, and experience with the use of Imatinib Zentiva in children with MDS/MPD, DFSP, GIST, and HES/CEL is very limited.
In some children and adolescents taking Imatinib Zentiva, growth may be slower than normal. The doctor will monitor growth during regular visits.

Imatinib Zentiva and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take, including those that are available without a prescription (such as paracetamol) and herbal medicines (such as St. John's Wort). Some medicines may affect the action of Imatinib Zentiva if taken at the same time. They may enhance or weaken the action of Imatinib Zentiva, which can lead to increased side effects or make Imatinib Zentiva less effective. Similarly, Imatinib Zentiva may affect certain other medicines.
The patient should tell their doctor if they are taking medicines to prevent blood clots.

Pregnancy, breastfeeding, and fertility

• In pregnancy and during breastfeeding, or if the patient suspects they are pregnant, or if they plan to become pregnant, they should consult a doctor before taking this medicine.
• Imatinib Zentiva is not recommended during pregnancy unless it is absolutely necessary, as it may harm the baby. The doctor will discuss the possible risks that may occur during treatment with Imatinib Zentiva during pregnancy.
• Women who may become pregnant should use effective contraception during treatment and for 15 days after the end of treatment.
• Breastfeeding should be avoided during treatment with Imatinib Zentiva and for 15 days after the end of treatment, as it may harm the baby.
• Patients interested in the impact of Imatinib Zentiva on fertility during its use should consult a doctor.

Driving and using machines

While taking this medicine, dizziness or drowsiness, or vision disturbances may occur. In this case, the patient should not drive vehicles or operate any tools or machines until they feel better.

3. How to take Imatinib Zentiva

The doctor has prescribed Imatinib Zentiva because of the patient's serious illness. Imatinib Zentiva may help treat this illness.
This medicine should always be taken according to the doctor's or pharmacist's recommendations. It is essential to take the medicine for as long as the doctor or pharmacist recommends. In case of doubts, the patient should consult a doctor or pharmacist.
The patient should not stop taking Imatinib Zentiva unless their doctor recommends it. If the patient cannot take the prescribed medicine or thinks they do not need it, they should immediately contact their doctor.

What dose of Imatinib Zentiva to take

Use in adult patients
The doctor will determine the exact number of Imatinib Zentiva tablets to take.

• In the case of CML treatment:The initial dose is usually 400 mg or 600 mg:
• 400 mg taken as four 100 mg tablets or one 400 mg tablet oncea day
• 600 mg taken as six 100 mg tablets or one 400 mg tablet and two 100 mg tablets oncea day.
• In the case of GIST treatment:The initial dose is 400 mg, taken as four 100 mg tablets or one 400 mg tablet oncea day.

In the case of CML and GIST treatment, the doctor may prescribe a higher or lower dose depending on the response to treatment. If the daily dose is 800 mg (eight 100 mg tablets or two 400 mg tablets), the patient should take four 100 mg tablets or one 400 mg tablet in the morning and four 100 mg tablets or one 400 mg tablet in the evening.

• In the case of Ph-positive ALL treatment:The initial dose is 600 mg, taken as six 100 mg tablets or one 400 mg tablet and two 100 mg tablets oncea day.
• In the case of MDS/MPD treatment:The initial dose is 400 mg, taken as four 100 mg tablets or one 400 mg tablet oncea day.
• In the case of HES/CEL treatment:The initial dose is 100 mg, taken as one 100 mg tablet oncea day. The doctor may decide to increase the dose to 400 mg taken as four 100 mg tablets or one 400 mg tablet oncea day, depending on the patient's response to treatment.
• In the case of DFSP treatment:The daily dose is 800 mg (eight 100 mg tablets or two 400 mg tablets), taken as four 100 mg tablets or one 400 mg tablet in the morning and four 100 mg tablets or one 400 mg tablet in the evening.

Use in children and adolescents

The doctor will determine how many Imatinib Zentiva tablets to give to the child. The dose of Imatinib Zentiva will depend on the child's condition, weight, and growth. The total daily dose in children should not exceed 800 mg in CML treatment and 600 mg in Ph-positive ALL treatment. Treatment may be given to the child once a day or alternatively, the daily dose may be divided into two (half the dose in the morning and half the dose in the evening).

When and how to take Imatinib Zentiva

• Imatinib Zentiva should be taken with a meal.This will help protect the patient from stomach problems when taking Imatinib Zentiva.
• Tablets should be swallowed whole, with a large glass of water.
• The tablet can be divided into two equal doses.

If the patient is unable to swallow tablets, they can dissolve them in a glass of non-carbonated water or apple juice:

• About 50 ml should be used for each 100 mg tablet and about 200 ml for each 400 mg tablet.
• Stir with a spoon until the tablets are completely dissolved.
• After dissolving the tablets, the patient should immediately drink the entire contents of the glass. Residues of the dissolved tablets may be left on the glass.

How long to take Imatinib Zentiva

Imatinib Zentiva should be taken every day for as long as the doctor recommends.

Taking a higher dose of Imatinib Zentiva than recommended

Patients who have accidentally taken too many tablets should immediatelytell their doctor, as they may require medical attention. They should take the packaging of the medicine with them.

Missing a dose of Imatinib Zentiva

• If the patient forgets to take a dose, they should take it as soon as they remember. However, if it is almost time for the next dose, they should skip the missed dose.
• Then, they should continue with their usual dosing schedule.
• They should not take a double dose to make up for the missed dose.

In case of any further doubts about taking this medicine, the patient should consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
They are usually mild to moderate.

Some side effects can be serious. The patient should immediately tell their doctor if they experience any of the following side effects:

Very common(may affect more than 1 in 10 people) or common(may affect less than 1 in 10 people) :

• Rapid weight gain. Imatinib Zentiva may cause water retention in the body (severe fluid retention).
• Infection symptoms, such as fever, severe chills, sore throat, or mouth sores. Imatinib Zentiva may decrease the number of white blood cells in the blood, which can increase the risk of infections.
• Unexpected bleeding or bruising (even without injury).

Uncommon(may affect less than 1 in 100 people) or rare(may affect less than 1 in 1000 people) :

• Chest pain, irregular heartbeat (symptoms of heart problems).
• Cough, difficulty breathing, or pain when breathing (symptoms of lung problems).
• Feeling of emptiness in the head, dizziness, or fainting (symptoms of low blood pressure).
• Feeling of nausea (nausea) with loss of appetite, dark urine, yellowing of the skin or eyes (symptoms of liver problems).
• Rash, redness of the skin with blisters on the lips, around the eyes, on the skin, or in the mouth, peeling of the skin, fever, swollen red or purple spots on the skin, itching, burning sensation, pustular rash (symptoms of skin problems).
• Severe abdominal pain, blood in vomit, stool, or urine, black stools (symptoms of stomach and intestine problems).
• Significantly reduced urine output, feeling of thirst (symptoms of kidney problems).
• Feeling of nausea (nausea) with diarrhea and vomiting, abdominal pain, or fever (symptoms of intestine problems).
• Severe headache, weakness, or paralysis of limbs or face, difficulty speaking, sudden loss of consciousness (symptoms of nervous system problems, such as bleeding or swelling in the skull/brain).
• Pallor, feeling of fatigue and shortness of breath, and dark urine (symptoms of red blood cell deficiency).
• Eye pain or vision disturbances, bleeding in the eyes.
• Bone or joint pain (symptoms of bone necrosis).
• Blisters on the skin or mucous membranes (symptoms of pemphigus).
• Numbness or feeling of cold in the fingers and toes (symptoms of Raynaud's syndrome).
• Sudden swelling and redness of the skin (symptoms of skin infection called cellulitis).
• Hearing difficulties.
• Muscle weakness and muscle cramps with irregular heartbeat (symptoms of changes in potassium levels in the blood).
• Bruising.
• Abdominal pain with nausea (nausea).
• Muscle cramps with fever, reddish-brown urine, pain, or muscle weakness (symptoms of muscle problems).
• Pelvic pain, sometimes with nausea and vomiting, with sudden vaginal bleeding, dizziness, or fainting due to low blood pressure (symptoms of ovary or uterus problems).
• Nausea, shortness of breath, irregular heartbeat, cloudy urine, fatigue, and (or) joint problems with accompanying laboratory abnormalities (e.g., high potassium, uric acid, and calcium levels and low phosphorus levels in the blood).
• Blood clots in small blood vessels (thrombotic microangiopathy).

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

• Co-occurrence of widespread, severe rash, nausea, fever, high levels of certain white blood cells, or yellowing of the skin or eyes (jaundice) with shortness of breath, chest pain/discomfort, significantly reduced urine output, and thirst, etc. (symptoms of an allergic reaction related to treatment).
• Chronic kidney failure.
• Reactivation (recurrence) of hepatitis B virus infection (liver infection) in patients who have had this disease in the past.

If the patient experiences any of the above side effects, they should immediately tell their doctor.

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

• Headache or fatigue.
• Feeling of nausea (nausea), vomiting, diarrhea, or indigestion.
• Rash.
• Muscle cramps or joint pain, muscle pain, or bone pain.
• Swelling, such as swelling of the ankles or eyes.
• Weight gain. If any of these side effects worsen, the patient should tell their doctor.

Common(may affect less than 1 in 10 people) :

• Lack of appetite, weight loss, or taste disturbances.
• Dizziness or weakness.
• Sleep disturbances (insomnia).
• Eye discharge with itching, redness, and swelling, excessive tearing, or blurred vision.
• Nosebleeds.
• Abdominal pain or swelling, bloating with gas, heartburn, or constipation.
• Itching.
• Excessive hair loss or thinning.
• Numbness of hands or feet.
• Mouth ulcers.
• Joint pain with swelling.
• Dry mouth, dry skin, or dry eyes.
• Decreased or increased skin sensitivity.
• Hot flashes, chills, or night sweats. If any of these side effects worsen, the patient should tell their doctor.

Uncommon(may affect less than 1 in 100 people):

• Painful red lumps on the skin, skin pain, redness of the skin (inflammation of the fatty tissue under the skin).
• Cough, runny nose, or stuffy nose, feeling of pressure or pain when pressing on the area above or to the sides of the nose, nasal congestion, sneezing, sore throat, which may be accompanied by headache (symptoms of upper respiratory tract infection).
• Severe headache, usually on one side of the head, which may be accompanied by nausea, vomiting, and sensitivity to light or sound (symptoms of migraine).
• Flu-like symptoms (flu).
• Pain or burning sensation when urinating, high fever, pain in the groin or pelvic area, red or brown urine, or cloudy urine (symptoms of urinary tract infection).
• Joint or muscle pain (symptoms of joint pain).
• Feeling of persistent sadness and loss of interest, preventing the patient from performing daily activities (symptoms of depression).
• Feeling of anxiety or apprehension with physical symptoms, such as rapid heartbeat, sweating, trembling, dry mouth (symptoms of anxiety).
• Drowsiness/excessive drowsiness.
• Trembling or muscle twitching.
• Memory disturbances.
• Irrepressible urge to move the legs (restless legs syndrome).
• Hearing noises (e.g., ringing, buzzing) in the ears that do not come from outside (tinnitus).
• High blood pressure (hypertension).
• Belching.
• Oral thrush.
• Difficulty swallowing.
• Increased sweating.
• Skin discoloration.
• Brittle nails.
• Red bumps or white pimples that form around the hair roots, which can cause pain, itching, or burning sensation (symptoms of folliculitis).
• Skin rash with peeling skin (exfoliative dermatitis).
• Breast enlargement (may occur in men or women).
• Dull pain and (or) feeling of heaviness in the testicles or in the lower abdomen, pain when urinating, during sexual intercourse, or during ejaculation, blood in the urine (symptoms of testicular swelling).
• Difficulty achieving or maintaining an erection (erectile dysfunction).
• Heavy or irregular menstrual bleeding.
• Difficulty achieving or maintaining sexual arousal.
• Decreased sex drive.
• Nipple pain.
• General malaise.
• Viral infection, such as a cold.
• Back pain due to kidney problems.
• Increased frequency of urination.
• Increased appetite.
• Pain or burning sensation in the upper abdomen and (or) chest (heartburn), nausea, vomiting, acid reflux, feeling of fullness, and bloating, black stools (symptoms of stomach ulcers).
• Stiffness of joints and muscles.
• Abnormal laboratory test results.

If any of the above side effects worsen, the patient should tell their doctor.
Rare(may affect less than 1 in 1000 people):

• Confusion.
• Nail discoloration.

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

• Redness and (or) swelling of the palms and soles, which may be accompanied by tingling and burning pain.
• Skin changes with pain and (or) blistering.
• Slowed growth in children and adolescents. If any of these side effects worsen, the patient should tell their doctor.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides of the Office for Registration of Medicinal Products, Medical Devices, and Biocides.
Al. Jerozolimskie 181 C

• 02 - 222 Warsaw Tel.: + 48 22 49 21 301 Fax: + 48 22 49 21 309 Website: www.smz.ezdrowie.gov.pl Side effects can also be reported to the marketing authorization holder or its representative in Poland. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Imatinib Zentiva

• The medicine should be stored out of sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and blister. The expiry date refers to the last day of the month.
• There are no special precautions for storing the medicine.
• Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Imatinib Zentiva contains

• The active substance of the medicine is imatinib mesylate. Each Imatinib Zentiva tablet contains imatinib mesylate equivalent to 100 mg of imatinib. Each Imatinib Zentiva tablet contains imatinib mesylate equivalent to 400 mg of imatinib.
• Other ingredients are: microcrystalline cellulose, low-substituted hydroxypropylcellulose, povidone, crospovidone (Type A), anhydrous colloidal silica, magnesium stearate.
• Tablet coating: hypromellose, macrogol 400, talc, iron oxide red (E 172), iron oxide yellow (E 172).

What Imatinib Zentiva looks like and contents of the pack

Imatinib Zentiva 100 mg film-coated tablets are dark yellow to brown-orange, round, 10.1 mm in diameter (± 5%) with a dividing line on one side and "100" on the other side. The tablet can be divided into equal doses.
Imatinib Zentiva 400 mg film-coated tablets are oval, dark yellow to brown-orange, 21.6 mm long and 10.6 mm wide (± 5%) with a dividing line on one side and "400" on the other side. The tablet can be divided into equal doses.
100 mg tablets are available in packs of 60 film-coated tablets.
400 mg tablets are available in packs of 30 film-coated tablets.

Marketing authorization holder

Zentiva k.s.,
U kabelovny 130, Dolni Měcholupy,
102 37 Prague 10, Czech Republic

Manufacturer

Remedica LTD
Limassol Industrial Estate, Aharnon Street,
P.O.Box 51706, 3508, Limassol, Cyprus
Pharmadox Healthcare Ltd
KW20A Kordin Industrial Park
Paola PLA 3000, Malta

To obtain more detailed information on the medicine and its names in the Member States of the European Economic Area, the patient should contact the representative of the marketing authorization holder in Poland:

Zentiva Poland Sp. z o.o.
Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00
Date of last revision of the leaflet:March 2023