Imatinib Krka d.d. 400 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Imatinib Krka d.d. 400 mg film-coated tablets EFG

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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, talk to your doctor, pharmacist or nurse, even if they are effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Imatinib Krka d.d. is and what it is used for
2. What you need to know before taking Imatinib Krka d.d.
3. How to take Imatinib Krka d.d.
4. Possible side effects
5. How to store Imatinib Krka d.d.
6. Contents of the pack and other information

1. What Imatinib Krka d.d. is and what it is used for

Imatinib Krka d.d. is a medicine that contains an active substance called imatinib. This medicine works by inhibiting the growth of abnormal cells in the diseases described below. These include certain types of cancer.

Imatinib is a treatment for adults and children for:

• Chronic myeloid leukaemia (CML). Leukaemia is a cancer of the white blood cells. These white cells normally help the body fight infections. Chronic myeloid leukaemia is a type of leukaemia in which certain abnormal white cells (called myeloid cells) begin to grow uncontrollably.

• Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). Leukaemia is a cancer of the white blood cells. These white cells normally help the body fight infections. Philadelphia chromosome-positive acute lymphoblastic leukaemia is a type of leukaemia in which abnormal white cells (called lymphoblasts) begin to grow uncontrollably. Imatinib inhibits the growth of these cells.

Imatinib is also a treatment for adults for:

• Myelodysplastic/myeloproliferative diseases (MDS/MPD). These are a group of blood disorders in which certain blood cells begin to grow uncontrollably. Imatinib inhibits the growth of these cells in a specific subtype 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 grow uncontrollably. Imatinib inhibits the growth of these cells in a specific subtype of these diseases.

• Gastrointestinal stromal tumours (GIST). GIST is a cancer of the stomach and intestine. It arises from uncontrolled cell growth in the supportive tissues of these organs.

• Dermatofibrosarcoma protuberans (DFSP). DFSP is a cancer of the tissue beneath the skin in which certain cells begin to grow uncontrollably. Imatinib inhibits the growth of these cells.

In the remainder of this leaflet, abbreviations will be used when referring to these diseases.

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

2. What you need to know before starting to take Imatinib Krka d.d.

Only a doctor experienced in medications for treating blood cell cancers or solid tumors will prescribe Imatinib Krka d.d. to you.

Carefully follow all instructions from your doctor, even if they differ from the general information contained in this leaflet.

Do not take Imatinib Krka d.d.

• if you are allergic to imatinib or to any of the other ingredients of this medicine (listed in section 6).

If this applies to you, inform your doctor and do not take Imatinib Krka d.d.

If you think you may be allergic but are not sure, consult your doctor.

Warnings and precautions

Talk to your doctor before starting to take Imatinib Krka d.d.:

• if you have or have had any liver, kidney, or heart problems.

• if you are taking the medicine levothyroxine because your thyroid has been removed.

• if you have ever had or might currently have an infection with the hepatitis B virus. This is because Imatinib Krka d.d. could cause hepatitis B to become active again, which can be fatal in some cases. Your doctor must carefully check for signs of this infection before starting treatment.

• if you develop bruising, bleeding, fever, fatigue, or confusion while taking Imatinib Krka d.d., please contact your doctor immediately. These could be signs of damage to blood vessels called thrombotic microangiopathy (TMA).

If any of these situations apply to you, inform your doctor before taking Imatinib Krka d.d.

You may become more sensitive to sunlight while taking Imatinib Krka d.d. It is important to cover skin areas exposed to sunlight and use high-protection sunscreen. These precautions also apply to children.

During treatment with Imatinib Krka d.d., inform your doctor immediately if you gain weight very rapidly. Imatinib Krka d.d. can cause fluid retention in the body (severe fluid retention).

While you are taking Imatinib Krka d.d., your doctor will regularly monitor whether the medicine is working. You will also have regular blood tests and be weighed regularly.

Children and adolescents

Imatinib Krka d.d. is also a treatment for children and adolescents with CML. There is no experience with children under 2 years of age with CML. Experience in children and adolescents with Ph-positive ALL is limited, and experience in children and adolescents with MDS/MPD, DFSP, and GIST is very limited.

Some children and adolescents taking Imatinib Krka d.d. may grow more slowly than normal. Your doctor will monitor growth during periodic visits.

Other medicines and Imatinib Krka d.d.

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription (such as paracetamol) and including herbal medicines (such as St. John’s wort). Some medicines may interfere with the effect of Imatinib Krka d.d. when taken together. These may increase or decrease the effect of Imatinib Krka d.d., leading to an increase in adverse effects or making Imatinib Krka d.d. less effective. Imatinib Krka d.d. may also have the same effect on other medicines.

Inform your doctor if you are taking medicines that prevent blood clots from forming.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.
• Use of Imatinib Krka d.d. during pregnancy is not recommended unless clearly necessary, as it may harm your baby. Your doctor will discuss with you the possible risks of taking Imatinib Krka d.d. during pregnancy.
• Women who could become pregnant are advised to use an effective method of contraception during treatment and for 15 days after stopping treatment.
• Do not breastfeed during treatment with Imatinib Krka d.d. or for the following 15 days after treatment ends, as it may harm your baby.
• Patients concerned about their fertility while taking Imatinib Krka d.d. should discuss this with their doctor.

Driving and use of machines

You may experience dizziness, drowsiness, or blurred vision while taking this medicine. If this occurs, do not drive or operate tools or machinery until you feel well again.

Imatinib Krka d.d. contains lactose

This medicine contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with him before taking this medicine.

3. How to take Imatinib Krka d.d.

Your doctor has prescribed this medicine because you suffer from a serious illness. Imatinib can help you fight this disease.

However, follow exactly the administration instructions for this medicine as indicated by your doctor or pharmacist. It is important that you do so for the length of time prescribed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Do not stop taking this medicine unless instructed by your doctor. If you are unable to take the medicine as prescribed or think you no longer need to take it, contact your doctor immediately.

How much to take of Imatinib Krka d.d.

Use in adults

Your doctor will tell you exactly how many tablets of this medicine you should take.

If you are being treated for CML:

Depending on your condition, the starting dose is 400 mg or 600 mg:

• 400 mg taken as one 400 mg tablet once daily.
• 600 mg taken as one 400 mg tablet plus two 100 mg tablets once daily.

If you are being treated for GIST:

The initial dose is 400 mg taken as one 400 mg tablet once daily.

For both CML and GIST, your doctor may prescribe a higher or lower dose depending on your response to treatment. If your daily dose is 800 mg (2 tablets of 400 mg), you should take one tablet in the morning and a second tablet in the evening.

If you are being treated for Ph-positive ALL:

The starting dose is 600 mg taken as one 400 mg tablet plus two 100 mg tablets once daily.

If you are being treated for MDS/MPN:

The starting dose is 400 mg taken as one tablet once daily.

If you are being treated for 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 one 400 mg tablet once daily, depending on your response to treatment.

If you are being treated for DFSP:

The dose is 800 mg per day (2 tablets of 400 mg), taken as one tablet in the morning and a second tablet in the evening.

Use in children and adolescents

Your doctor will determine how many imatinib tablets to give the child. The amount of imatinib administered will depend on the child's condition, body weight, and height. The total daily dose in children and adolescents with CML should not exceed 800 mg, nor 600 mg in Ph-positive ALL. The treatment may be given to the child once daily or, alternatively, the dose may be divided into two administrations (half in the morning and half in the evening).

When and how to take the medicine

• Take Imatinib with food. This will help protect you from stomach problems while taking this medicine.
• Swallow the tablets with a large glass of water.

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

• Use about 50 ml for each 100 mg tablet.
• Use about 200 ml for each 400 mg tablet.
• Stir with a spoon until the tablets are completely dissolved.
• Once the tablet has dissolved, drink the entire contents of the glass immediately. There may be residue from the dissolved tablets remaining in the glass.

How long to take Imatinib Krka d.d.

Continue taking imatinib every day for as long as your doctor tells you.

If you take more Imatinib Krka d.d. than you should

If you have accidentally taken too many tablets, speak to your doctor immediately. You may require medical attention. Bring the medicine packaging with you.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone: 915620420, stating the medicine and the amount ingested.

If you forget to take Imatinib Krka d.d.

• 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 questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them. These are usually mild to moderate.

Some adverse effects may be serious. Immediately inform your doctor if you experience any of the following:

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

• Rapid weight gain. Imatinib Krka d.d. may cause your body to retain fluid (severe fluid retention).
• Signs of infection such as fever, severe chills, sore throat, or mouth ulcers. Imatinib Krka d.d. may reduce the number of white blood cells in your blood, making you more susceptible to infections.
• Unexpected bleeding or bruising (when you have not sustained an 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 (signs of heart problems).
• Cough, with difficulty breathing or painful breathing (signs of lung problems).
• Dizziness, lightheadedness, or fainting (signs of low blood pressure).
• Nausea, loss of appetite, dark-colored urine, yellowing of the skin or eyes (signs of liver problems).
• Rash, skin redness, blisters on the lips, eyes, skin, or mouth, skin peeling, fever, red or purple skin spots, itching, burning sensation, pustular rash (signs of skin problems).
• Severe abdominal pain, blood in vomit, stools, or urine, black stools (signs of gastrointestinal disturbances).
• Marked decrease in urine output, feeling thirsty (signs of kidney problems).
• Nausea, with diarrhea and vomiting, abdominal pain, or fever (signs of intestinal problems).
• Severe headache, weakness or paralysis in limbs or face, difficulty speaking, sudden loss of consciousness (signs of nervous system problems such as bleeding or swelling in the skull/brain).
• Pale skin, feeling tired and short of breath, dark-colored urine (signs of low red blood cell count).
• Eye pain or vision disturbances, bleeding in the eyes.
• Bone or joint pain (signs of osteonecrosis).
• Blisters on the skin or mucous membranes (signs of pemphigus).
• Hip pain or difficulty walking.
• Numbness or cold sensation in feet and fingers (signs of Raynaud's syndrome).
• Sudden swelling and redness of the skin (sign of a skin infection called cellulitis).
• Hearing difficulties.
• Muscle weakness and muscle spasms, with an abnormal heartbeat (signs of changes in blood potassium levels).
• Bruising.
• Stomach pain with nausea.
• Muscle spasms with fever, red-brown urine, muscle pain or weakness (signs of muscle problems).
• Pelvic pain sometimes with nausea and vomiting, unexpected vaginal bleeding, dizziness or fainting due to low blood pressure (signs of problems in ovaries or uterus).
• Nausea, difficulty breathing, irregular heartbeat, cloudy urine, fatigue and/or joint discomfort associated with abnormal laboratory test results (e.g. elevated 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 (frequency cannot be estimated from available data):

• Combination of severe widespread rash, feeling unwell, fever, elevated levels of certain white blood cells or yellowing of the skin or eyes (jaundice), difficulty breathing, chest pain/discomfort, severely reduced urine output, and feeling thirsty, etc. (signs of a treatment-related allergic reaction).
• Chronic kidney failure.
• Reactivation of hepatitis B virus infection if you have previously had hepatitis B (a liver infection).

If you experience any of the above conditions, inform your doctor immediately.

Other adverse effects may include:

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

• Headache or feeling tired.
• Nausea, vomiting, diarrhea, or indigestion.
• Rash.
• Muscle cramps or joint, muscle, or bone pain during treatment with imatinib or when stopping imatinib treatment.
• Swelling such as swollen ankles or eyes.
• Weight gain.

If any of these affect you significantly, inform your doctor.

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

• Anorexia, weight loss, or altered sense of taste.
• Feeling tired or weak.
• Difficulty sleeping (insomnia).
• Watery, itchy, red, and swollen eyes, watery eyes, or blurred vision (conjunctivitis).
• Nosebleeds.
• Pain or swelling in your abdomen, flatulence, heartburn, or constipation.
• Itching.
• Unusual hair thinning or hair loss.
• 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 affect you significantly, consult your doctor.

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

• Painful red lumps on the skin, skin pain, skin redness (inflammation of fatty tissue under the skin).
• Cough, runny or blocked nose, feeling of heaviness or pain when pressing the area around the eyes or sides of the nose, nasal congestion, sneezing, sore throat, with or without headache (signs of upper respiratory tract infection).
• Severe headache, like a stabbing pain or pulsating sensation, usually on one side of the head, often accompanied by nausea, vomiting, and sensitivity to light or sound (signs of migraine).
• Flu-like symptoms (influenza).
• Pain or burning sensation when urinating, fever, groin or pelvic pain, cloudy or reddish-brown urine (signs of urinary tract infection).
• Joint pain and swelling (signs of arthralgia).
• Persistent feeling of sadness and loss of interest, interfering with normal daily life (signs of depression).
• Feeling of apprehension and worry along with physical symptoms such as palpitations, sweating, trembling, dry mouth (signs of anxiety).
• Numbness/sleepiness/excessive sleepiness.
• Tremors or involuntary movements (tremor).
• Memory impairment.
• Irresistible urge to move the legs (restless legs syndrome).
• Hearing noises (e.g. ringing, buzzing) in the ears not originating from outside (tinnitus).
• High blood pressure (hypertension).
• Belching or gas.
• Swelling of the lips.
• Difficulty swallowing.
• Increased sweating.
• Skin discoloration.
• Brittle nails.
• Red bumps or pimples around hair roots, possibly painful, itchy, or burning (signs of inflammation of hair follicles, also called folliculitis).
• Skin rash with peeling or shedding of the skin (exfoliative dermatitis).
• Breast enlargement (can occur in men or women).
• Dull and/or heavy sensation in testicles or lower abdomen, pain when urinating, during sexual intercourse, or ejaculation, blood in urine (signs of testicular edema).
• Inability to achieve or maintain an erection (erectile dysfunction).
• Heavy or irregular menstrual periods.
• Difficulty achieving/maintaining sexual arousal.
• Decreased sexual desire.
• Nipple pain.
• General feeling of being unwell (malaise).
• Viral infections such as cold sores.
• Lower back pain due to kidney disorder.
• 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 (signs of stomach ulcer).
• Stiffness in joints or muscles.
• Abnormal laboratory test results.

If any of these affect you significantly, consult your doctor.

Rare (may affect up to 1 in 1,000 patients):

• Confusion.
• An episode of seizures and reduced consciousness (convulsions).
• Discoloration of the nails.

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

• Redness and/or swelling of the palms of the hands and soles of the feet, which may be accompanied by tingling and burning pain.
• Painful and/or blistering skin lesions.
• Delayed growth in children and adolescents.

If any of these affect you significantly, consult your doctor.

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Imatinib Krka d.d.

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

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and any unused medicines at a pharmacy’s SIGRE collection point. If you are unsure, ask your pharmacist how to properly dispose of containers and unused medicines. This will help protect the environment.

6. Contents of the pack and other information

Composition of Imatinib Krka d.d.

• The active substance is imatinib (as mesilate).

Each tablet contains 400 mg of imatinib (as mesilate).

• The other components are: tablet core: lactose monohydrate, maize starch, hydroxypropylcellulose, microcrystalline cellulose (E460), crospovidone, colloidal anhydrous silica, magnesium stearate (E470b); coating: polyvinyl alcohol, titanium dioxide (E171), macrogol, talc, red iron oxide (E172), yellow iron oxide (E172).

See section 2 “Imatinib Krka d.d contains lactose”.

Appearance of the product and contents of the pack

Film-coated tablets, orange-brown, oval-shaped (dimensions: 22 mm x 9 mm), biconvex.

Blister pack: 10, 30, 60 and 90 film-coated tablets in a box.

Only some pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

KRKA, d.d.,

Novo mesto, Šmarješka cesta 6,

8501 Novo mesto,

Slovenia

Manufacturer:

KRKA, d.d.,

Novo mesto, Šmarješka cesta 6,

8501 Novo mesto,

Slovenia

or

TAD Pharma GmbH,

Heinz-Lohmann-Str. 5,

D-27472 Cuxhaven,

Germany

or

KRKA – FARMA d.o.o.,

Holjevca 20/E,

10450 Jastrebarsko,

Croatia

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

KRKA Farmacéutica, S.L.,

C/ Anabel Segura 10, 28108

Alcobendas, Madrid,

Spain

This medicinal product is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Member State	Medicinal product name
Czech Republic	Imatinib HCS 400 mg
Austria	Imatinib Krka d.d. 400 mg Filmtabletten
Belgium	Imatinib Krka d.d. 400 mg filmomhulde tabletten
Spain	Imatinib Krka d.d. 400 mg film-coated tablets
Finland	Imatinib Krka d.d. 400 mg kalvopäällysteinen
France	Imatinib HCS d.d. 400 mg comprimé pelliculé
Sweden	Imatinib Krka d.d. 400 mg filmdragerade tabletter
United Kingdom	Imatinib 400 mg film-coated tablets
Ireland	Imatinib Krka d.d. 400 mg film-coated tablets
Portugal	Imatinib Krka d.d. 400 mg film-coated tablet

Date of the most recent review of this leaflet: May 2024

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