Imatinib zentiva: detailed information

Package leaflet: Information for the patient

Imatinib Zentiva, 100 mg, film-coated tablets
Imatinib Zentiva, 400 mg, film-coated tablets
Imatinibum
Please read this leaflet carefully before taking this medicine because it contains important
information for you.

Keep this leaflet as 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 person. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

What Imatinib Zentiva is and what it is used for
Important information before taking Imatinib Zentiva
How to take Imatinib Zentiva
Possible side effects
How to store Imatinib Zentiva
Contents of the pack and other information

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

Imatinib Zentiva is a medicine containing the active substance called imatinib. This medicine works by
inhibiting the growth of abnormal cells in the diseases listed below. These include certain types of
cancer.
Imatinib Zentiva is used to treat adult patients and children with:

Chronic myeloid leukaemia (CML). Leukaemia is a cancer of white blood cells. Normally, white blood cells help the body fight infections. Chronic myeloid leukaemia is a type of leukaemia 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 known as "blast crisis". However, in children and adolescents it may be used to treat all stages of the disease.
Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph-positive ALL). Leukaemia is a cancer arising from white blood cells. Normally, white blood cells help the body fight infections. Acute lymphoblastic leukaemia is a type of leukaemia 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 diseases (MDS/MPD). These are groups of blood disorders 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) and/or chronic eosinophilic leukaemia (CEL). These are blood disorders in which certain blood cells (called eosinophils) begin to multiply uncontrollably. Imatinib inhibits the growth of these cells in certain subtypes of these disorders.
Gastrointestinal stromal tumours (GIST). GIST is a tumour of the stomach and intestines. It arises due to uncontrolled growth of connective tissue cells in these organs.
Dermatofibrosarcoma protuberans (DFSP). DFSP is a tumour of the skin and subcutaneous tissues in which certain cells begin to multiply uncontrollably. Imatinib Zentiva inhibits the growth of these cells.

In the remainder of this leaflet, the abbreviations of the disease names listed above will be used.
If you have any questions about how this medicine works or why it has been prescribed, please ask your doctor.
2. Important information before taking Imatinib Zentiva
Imatinib Zentiva will only be prescribed by doctors experienced in the use of medicines for treating blood cancers or solid tumours.
You must strictly follow your doctor's instructions, even if they differ from the general information provided in this leaflet.
When not to use Imatinib Zentiva:

if you are allergic to imatinib or any of the other ingredients of this medicine (listed in section 6). If this applies to you, please tell your doctor before taking Imatinib Zentiva.

If you suspect an allergy but are unsure, please consult your doctor.
Warnings and precautions
Before starting Imatinib Zentiva, speak to your doctor:

if you have or have ever had liver, kidney or heart disease.
if you are taking levothyroxine after removal of the thyroid gland.
if you have ever had or may currently have hepatitis B virus infection; this is because Imatinib Zentiva may cause reactivation of hepatitis B virus infection, which in some cases may be fatal; patients will be closely monitored by their doctor for signs of this infection before starting treatment.
if you develop bruising, bleeding, fever, fatigue or confusion while taking Imatinib Zentiva, contact your doctor immediately. These may be symptoms of a blood vessel disorder called thrombotic microangiopathy (TMA).

If any of the points listed above apply to you, please tell your doctor before taking Imatinib Zentiva.
While taking Imatinib Zentiva, you may become more sensitive to sunlight. It is important to cover areas of skin exposed to sunlight and to use sunscreen products with a high sun protection factor (SPF). These precautions should also be taken for children.
You must immediately inform your doctor if you experience a rapid increase in body weight during treatment with Imatinib Zentiva. Imatinib Zentiva may cause fluid retention (severe fluid retention).
While taking Imatinib Zentiva, your doctor will regularly assess whether treatment with Imatinib Zentiva is effective. You will also have regular blood tests and body weight measurements.
Children and adolescents
Imatinib Zentiva is also used to treat children with CML. There is no experience with use in children under 2 years of age with CML. Experience with use in children with Ph-positive ALL is limited, and experience with use in children with MDS/MPD, DFSP, GIST and HES/CEL is very limited.
Some children and adolescents taking Imatinib Zentiva may experience slower than normal growth. Your doctor will monitor growth during regular visits.
Imatinib Zentiva with other medicines
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those obtained without a prescription (such as paracetamol) and herbal medicines (such as St John's wort). Some medicines may affect the action of Imatinib Zentiva when taken at the same time. They may increase or decrease the effect of Imatinib Zentiva, which may lead to increased side effects or make Imatinib Zentiva less effective. In the same way, Imatinib Zentiva may affect the action of some other medicines.
Tell your doctor if you are taking medicines to prevent blood clots.

Pregnancy, breastfeeding and effects on fertility

If you are pregnant, breastfeeding, think you may be pregnant or are planning to become pregnant, you must consult your doctor before taking this medicine.
Imatinib Zentiva is not recommended during pregnancy unless absolutely necessary, as it may harm the unborn child. Your doctor will discuss the potential risks associated with taking Imatinib Zentiva during pregnancy.
Women who can become pregnant should use an effective method of contraception during treatment and for 15 days after stopping treatment.
Breastfeeding must be avoided during treatment with Imatinib Zentiva and for 15 days after stopping treatment, as it may harm the infant.
Patients concerned about the effect of Imatinib Zentiva on fertility during treatment should consult their doctor.

Driving and using machines
While taking this medicine, dizziness, drowsiness or blurred vision may occur. If this happens, do not drive or operate tools or machinery until you feel well again.

3. How to take Imatinib Zentiva

Your doctor has prescribed Imatinib Zentiva because you have a serious condition. Imatinib Zentiva may
help in treating this disease.
This medicine should always be taken exactly as directed by your doctor or pharmacist. It is important to
take the medicine for as long as your doctor or pharmacist has advised. If in doubt, consult your doctor or
pharmacist.
Do not stop taking Imatinib Zentiva unless your doctor tells you to. If you are unable to take the medicine
prescribed by your doctor or think you no longer need it, you should contact your doctor immediately.

What dose of Imatinib Zentiva should be taken
Use in adult patients
Your doctor will determine the exact number of Imatinib Zentiva tablets to take.

For treatment of CML: Depending on the patient's condition, the usual starting dose is 400 mg or 600 mg:
- 400 mg taken as four 100 mg tablets or one 400 mg tablet once daily
- 600 mg taken as six 100 mg tablets or one 400 mg tablet and two 100 mg tablets once daily.
For treatment of GIST: The starting dose is 400 mg, taken as four 100 mg tablets or one 400 mg tablet once daily.

For treatment of both CML and GIST, your doctor may prescribe a higher or lower dose depending on
response to treatment. If the daily dose is 800 mg (eight 100 mg tablets or two 400 mg tablets), 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.

For treatment of Ph-positive ALL: The starting dose is 600 mg, taken as six 100 mg tablets or one 400 mg tablet and two 100 mg tablets once daily.
For treatment of MDS/MPD: The starting dose is 400 mg, taken as four 100 mg tablets or one 400 mg tablet once daily.
For treatment of HES/CEL: The starting dose is 100 mg, taken as one 100 mg tablet once daily. Your doctor may decide to increase the dose to 400 mg, taken as four 100 mg tablets or one 400 mg tablet once daily, depending on the patient's response to treatment.
For treatment of DFSP: 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
Your doctor will determine how many Imatinib Zentiva tablets should be given to the child. The dose of
Imatinib Zentiva will depend on the child's condition, body weight and height. The total daily dose in children must not
exceed 800 mg in the treatment of CML and 600 mg in the treatment of Ph-positive ALL. The medicine may be
given once daily or alternatively the daily dose may be divided into two (half the dose in the morning and half in the evening).

When and how to take Imatinib Zentiva

Imatinib Zentiva should be taken with a meal. This will help protect you from stomach problems while taking Imatinib Zentiva.
Swallow the tablets whole with a large glass of water.
A tablet may be divided into two equal doses.

If you are unable to swallow the tablets, you may dissolve them in a glass of still water or apple juice:

Use approximately 50 ml 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, drink the entire contents of the glass immediately. Traces of dissolved tablets may remain in the glass.

How long to take Imatinib Zentiva
Take Imatinib Zentiva every day for as long as your doctor has advised.
Taking more than the recommended dose of Imatinib Zentiva
Patients who have accidentally taken too many tablets should immediately inform their doctor, as they may
require medical care. Take the medicine packaging with you.
Missing a dose of Imatinib Zentiva

If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose.
Then continue with your regular dosing schedule.
Do not take a double dose to make up for a missed dose.

If you have any further doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will get them.
They are usually mild to moderate.
Some side effects may be serious. You must tell your doctor immediately if any of the
following side effects occur:
Very common (may affect more than 1 in 10 people) or common (may affect up to 1 in 10 people):

Rapid weight gain. Imatinib Zentiva may cause fluid retention (severe fluid retention).
Signs of infection such as fever, severe chills, sore throat or mouth ulcers. Imatinib Zentiva may reduce the number of white blood cells in the blood, which may increase susceptibility to infections.
Unexpected bleeding or bruising (despite no injury).

Uncommon (may affect up to 1 in 100 people) or rare (may affect up to 1 in 1,000 people):

Chest pain, irregular heartbeat (symptoms of heart problems).
Cough, difficulty breathing or pain when breathing (symptoms of lung problems).
Feeling faint, dizziness or fainting (symptoms of low blood pressure).
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, skin peeling, fever, raised red or purple spots on the skin, itching, burning sensation, acne-like rash (symptoms of skin problems).
Severe abdominal pain, presence of blood in vomit, stool or urine, black stools (symptoms of gastrointestinal disorders).
Significantly reduced urine output, feeling thirsty (symptoms of kidney problems).
Nausea with diarrhoea and vomiting, abdominal pain or fever (symptoms of intestinal 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 within the skull/brain).
Pale skin, feeling tired and breathless, and dark urine (symptoms of red blood cell deficiency).
Eye pain or worsening vision, bleeding in the eyes.
Bone or joint pain (symptoms of bone necrosis).
Blisters on the skin or mucous membranes (symptoms of blistering disorders).
Numbness or cold sensation in fingers and toes (symptoms of Raynaud's syndrome).
Sudden swelling and redness of the skin (symptoms of skin infection known as connective tissue inflammation).
Hearing difficulties.
Muscle weakness and cramps with irregular heartbeat (symptoms of altered potassium levels in the patient's blood).
Bruising.
Stomach pain with nausea.
Muscle cramps with fever, red-brown discoloration of urine, muscle pain or weakness (symptoms of muscle problems).
Pelvic pain, sometimes with nausea and vomiting, sudden vaginal bleeding, dizziness or fainting due to low blood pressure (symptoms of ovarian or uterine problems).
Nausea, shortness of breath, irregular pulse, cloudy urine, fatigue and (or) joint problems accompanied by abnormal laboratory test results (e.g. high levels of potassium, uric acid and calcium, and low levels of phosphorus in the blood).
Blood clots in small blood vessels (thrombotic microangiopathy).

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

Co-occurrence of widespread severe rash, nausea, fever, high number 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 of hepatitis B virus infection in patients who previously had this disease.

If any of the above side effects occur, you must tell your doctor immediately.
Other side effects may include:
Very common (may affect more than 1 in 10 people):

Headache or fatigue.
Nausea, vomiting, diarrhoea or indigestion.
Rash.
Muscle or joint cramps, muscle or bone pain.
Swelling, such as in the ankles or around the eyes.
Weight gain. If any of these symptoms worsen, you must inform your doctor.

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

Loss of appetite, weight loss or taste disturbances.
Dizziness or weakness.
Sleep disturbances (insomnia).
Eye discharge with itching, redness and swelling (conjunctivitis), excessive tearing or blurred vision.
Nosebleeds.
Pain or swelling in the abdomen, bloating with flatulence, heartburn or constipation.
Itching.
Excessive hair loss or thinning.
Numbness in hands or feet.
Mouth ulcers.
Joint pain with swelling.
Dry mouth, dry skin or dry eyes.
Decreased or increased skin sensitivity.
Hot flushes, chills or night sweats. If any of these symptoms worsen, you must inform your doctor.

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

Painful red nodules on the skin, skin pain, redness of the skin (inflammation of the fatty tissue beneath the skin).
Cough, watery nasal discharge or nasal congestion, feeling of pressure or pain upon pressing the area above the eyes or on both sides of the nose, nasal mucosa congestion, sneezing, sore throat, with or without headache (symptoms of upper respiratory tract infection).
Severe headache felt as a pulsating pain or sensation of pulsation, usually on one side of the head, often accompanied by nausea, vomiting and sensitivity to light or sound (symptoms of migraine).
Flu-like symptoms (influenza).
Pain or burning sensation when urinating, elevated body temperature, pain in the groin or pelvic area, red or brown discoloration of urine or cloudy urine (symptoms of urinary tract infection).
Pain and swelling in joints (symptoms of joint pain).
Persistent feeling of sadness and loss of interest, preventing the patient from performing daily activities (symptoms of depression).
Feeling nervous or anxious with somatic symptoms such as rapid heartbeat, sweating, trembling, dry mouth (symptoms of anxiety).
Drowsiness / excessive sleepiness.
Tremor or muscle tremors.
Memory disturbances.
Irresistible urge to move legs (restless legs syndrome).
Hearing noises (e.g. ringing, buzzing) in the ears not originating from outside (tinnitus).
High blood pressure (hypertension).
Belching.
Inflammation of the lips.
Difficulty swallowing.
• Excessive sweating.
Skin discoloration.
Brittle nails.
Red nodules or whiteheads forming around hair roots, which may cause pain, itching or burning sensation (symptoms of folliculitis).
Skin rash with skin peeling (exfoliative dermatitis).
Breast enlargement (may occur in men or women).
Dull pain and (or) heaviness in the testicles or lower abdomen, pain when urinating, during sexual intercourse or ejaculation, blood in urine (symptoms of testicular swelling).
Inability to achieve or maintain erection (erectile dysfunction).
Heavy or irregular menstrual bleeding.
Difficulty achieving/maintaining sexual arousal.
Reduced libido.
Nipple pain.
General malaise.
Viral infection such as a cold.
Lower 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, gastric acid reflux, feeling of fullness and bloating, black stools (symptoms of stomach ulcer).
Stiffness of joints and muscles.
Abnormal laboratory test results.

If any of the above symptoms worsen, you must inform your doctor.
Rare (may affect up to 1 in 1,000 people):

Confusion.
Discoloration of nails.

Frequency not known (cannot be estimated from 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) blister formation.
Slowed growth in children and adolescents. If any of these symptoms worsen, you must inform your doctor.

Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, you should tell your doctor, pharmacist or nurse.
Side effects can also be reported directly to the Department for Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products.
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 authorisation holder or its representative in Poland.
Reporting side effects helps provide more information on the safety of using the medicine.

5. How to store Imatinib Zentiva

Keep this medicine out of the 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 stated month.
No special storage conditions apply.
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 other information

What Imatinib Zentiva contains

The active substance is imatinib mesilate. Each tablet of Imatinib Zentiva contains imatinib mesilate equivalent to 100 mg of imatinib. Each tablet of Imatinib Zentiva contains imatinib mesilate equivalent to 400 mg of imatinib.
The other ingredients are: microcrystalline cellulose, low-substituted hydroxypropyl cellulose, povidone, crospovidone (Type A), colloidal anhydrous 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 brownish-orange, round, with a diameter of 10.1 mm (± 5%), marked with a score 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-shaped, dark yellow to brownish-orange, measuring 21.6 mm in length and 10.6 mm in width (± 5%), with a score line on one side and "400" on the other side. The tablet can be divided into equal doses.
The 100 mg tablets are supplied in packs containing 60 film-coated tablets.
The 400 mg tablets are supplied in packs containing 30 film-coated tablets.

Marketing Authorisation 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

For more detailed information about the medicine and its names in the Member States of the
European Economic Area, please contact the local representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00