IMATINIB KRKA D.D. 400 mg FILM-COATED TABLETS

Introduction

Patient Information: Summary of Product Characteristics

Imatinib Krka d.d. 400 mg film-coated tabletsEFG

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, pharmacist, or nurse.
• 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Imatinib Krka d.d. is and what it is used for
2. What you need to know before you take Imatinib Krka d.d.
3. How to take Imatinib Krka d.d.
4. Possible side effects
5. Storage of 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 the active substance imatinib. This medicine works by inhibiting the growth of abnormal cells in the diseases described below. These include some types of cancer.

Imatinib is a treatment for adults and children for:

• Chronic myeloid leukemia (CML).Leukemia is a cancer of the white blood cells. These white blood cells normally help the body fight infections. Chronic myeloid leukemia is a type of leukemia in which certain abnormal white blood cells (called myeloid cells) start to grow out of control.

• Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).Leukemia is a cancer of the white blood cells. These white blood cells normally help the body fight infections. Acute lymphoblastic leukemia is a type of leukemia in which certain abnormal white blood cells (called lymphoblasts) start to grow out of control. Imatinib inhibits the growth of these cells.

Imatinib is also a treatment for adults for:

• Mycloproliferative disorders (MPD).These are a group of diseases of the blood in which some blood cells start to grow out of control. Imatinib inhibits the growth of these cells in a certain subtype of these diseases.

• Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL).These are diseases of the blood in which certain blood cells (called eosinophils) start to grow out of control. Imatinib inhibits the growth of these cells in a certain subtype of these diseases.
• Gastrointestinal stromal tumors (GISTs).GIST is a cancer of the stomach and intestine. It originates from uncontrolled cell growth of the supporting tissues of these organs.

• Dermatofibrosarcoma protuberans (DFSP).DFSP is a cancer of the tissue under the skin in which certain cells start to grow out of control. Imatinib inhibits the growth of these cells.

In the rest of this leaflet, the 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 you take Imatinib Krka d.d.

Imatinib Krka d.d. will only be prescribed for you by a doctor who has experience in medicines for treating blood cell cancers or solid tumors.

Follow carefully all instructions given by your doctor, even if they are different from the general information contained in this leaflet.

Do not take Imatinib Krka d.d.

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

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

If you think you may be allergic but are not sure, ask your doctor for advice.

Warnings and precautions

Talk to your doctor before taking Imatinib Krka d.d.:

• if you have or have had liver, kidney, or heart problems.
• if you are taking the medicine levothyroxine because you have had your thyroid removed.

• if you have ever had or might currently have a hepatitis B virus infection. This is because Imatinib Krka d.d. could cause the hepatitis B virus to become active again, which can be fatal in some cases. Your doctor should check carefully for signs of this infection before starting treatment.
• if while taking Imatinib Krka d.d. you develop bruising, bleeding, fever, fatigue, and confusion, please contact your doctor. This could be a sign of blood vessel damage called thrombotic microangiopathy (TMA).

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

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

During treatment with Imatinib Krka d.d., tell your doctor immediatelyif you gain weight very quickly. Imatinib Krka d.d. can cause water retention in the body (severe fluid retention).

While taking Imatinib Krka d.d., your doctor will regularly check if 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 in children with CML under 2 years of age. The experience in children and adolescents with Ph+ ALL is limited, and the experience in children and adolescents with MPD, DFSP, and HES/CEL is very limited.

Some children and adolescents taking Imatinib Krka d.d. may have slower than normal growth. The doctor will monitor growth during regular visits.

Other medicines and Imatinib Krka d.d.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those bought 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. They may increase or decrease the effect of Imatinib Krka d.d., leading to an increased risk of side effects or making Imatinib Krka d.d. less effective. Imatinib Krka d.d. may have the same effect on other medicines.

Tell your doctor if you are using medicines that prevent blood clots.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine.
• Imatinib Krka d.d. is not recommended during pregnancy unless clearly necessary, as it may harm your baby. Your doctor will discuss with you the potential 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 finishing treatment.
• Do not breastfeed while taking Imatinib Krka d.d. and for 15 days after finishing treatment, as it may harm your baby.
• Patients concerned about their fertility while taking Imatinib Krka d.d. should consult their doctor.

Driving and using machines

You may feel dizzy or drowsy or have blurred vision while taking this medicine. If this happens, do not drive or use tools or machines until you feel better.

Imatinib Krka d.d. contains lactose

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

3. How to take Imatinib Krka d.d.

Your doctor has prescribed this medicine for you because you have a serious illness. Imatinib can help you fight this illness.

However, follow exactly the instructions for taking this medicine given by your doctor or pharmacist. It is important to do so for the time period your doctor or pharmacist tells you. If you are in doubt, consult your doctor or pharmacist again.

Do not stop taking this medicine unless your doctor tells you to do so. If you cannot take the medicine as your doctor has prescribed or think you no longer need 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 to take.

If you are being treated for CML:

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

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

If you are being treated for GIST:

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

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

If you are being treated for Ph+ ALL:

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

If you are being treated for MPD:

The starting dose is 400 mg taken as one tablet oncea day.

If you are being treated for HES/CEL:

The starting dose is 100 mg taken as one 100 mg tablet oncea day.

Your doctor may decide to increase the dose to 400 mg taken as one 400 mg tablet oncea day, depending on how you respond to treatment.

If you are being treated for DFSP:

The dose is 800 mg a 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 tell you how many tablets of imatinib to give to the child. The amount of imatinib given will depend on the child's situation, body weight, and height. The total daily dose in children and adolescents with CML must not exceed 800 mg and 600 mg in Ph+ ALL. The treatment can be given to the child once a day or, alternatively, the dose can be divided into two doses (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 can dissolve them in a glass of still or sparkling 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.
• Drink the whole contents of the glass immediately. There may be leftover bits of the dissolved tablets in the glass.

For how long to take Imatinib Krka d.d.

Keep taking imatinib every day for the time period your doctor tells you.

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

If you accidentally take too many tablets, talk to your doctor immediately. You may need medical attention. Take the medicine pack with you.

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

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 the next dose, skip the missed dose.
• Then continue with your normal schedule.
• Do not take a double dose to make up for missed doses.

If you have any other 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 all people suffer from them. These are usually mild to moderate.

Some adverse effects can be serious. Inform your doctor immediately if you suffer from any of the following:

Very frequent adverse effects(may affect more than 1 in 10 people) or frequent(may affect up to 1 in 10 people):

• Rapid weight gain. Imatinib Krka d.d. may cause your body to retain water (severe fluid retention).
• Signs of infection such as fever, intense chills, sore throat, or ulcers in the mouth. Imatinib Krka d.d. may reduce the number of white blood cells in your blood, so you may suffer from infections more easily.
• Bleeding or bruising unexpectedly (when you have not suffered any injury).

Uncommon adverse effects(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, difficulty breathing, or painful breathing (signs of lung problems).
• Dizziness, lightheadedness, or fainting (signs of low blood pressure).
• Nausea, loss of appetite, dark urine, yellow skin or eyes (signs of liver problems).
• Rash, redness of the skin, with blisters on the lips, eyes, skin, or mouth, skin peeling, fever, red or purple skin spots, itching, burning sensation, rash with pus (signs of skin problems).
• Severe abdominal pain, blood in your vomit, stools, or urine, black stools (signs of gastrointestinal disorders).
• Significant decrease in urine output, feeling of thirst (signs of kidney problems).

• Nausea, with diarrhea and vomiting, abdominal pain, or fever (signs of intestinal problems).
• Severe headache, weakness, or paralysis in the limbs or face, difficulty speaking, sudden loss of consciousness (signs of problems in the nervous system such as bleeding or swelling in the skull/brain).

• Pale skin, feeling of tiredness, and difficulty breathing, dark urine (signs of low red blood cell count in the blood).
• Pain in the eyes or vision disorders, bleeding in the eyes.
• Pain in the bones or joints (signs of osteonecrosis).
• Blisters on the skin or mucous membranes (signs of pemphigus).
• Pain in the hip or difficulty walking.
• Numbness or feeling of cold in the feet and toes (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 potassium levels in the blood).
• Bruising.
• Stomach pain with nausea.
• Muscle spasms with fever, reddish-brown urine, pain, or weakness in your muscles (signs of muscle problems).
• Pain in the pelvis sometimes with nausea and vomiting, with unexpected vaginal bleeding, feeling of dizziness or fainting due to low blood pressure (signs of problems in the ovaries or uterus).
• Nausea, difficulty breathing, irregular heartbeat, cloudy urine, tiredness, and/or joint discomfort associated with 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).

Unknown frequency(frequency cannot be estimated from available data):

• Combination of extensive intense rash, feeling of discomfort, fever, high levels of certain white blood cells, or yellow skin and eyes (signs of jaundice) with difficulty breathing, chest pain, decreased urine production, and feeling of thirst, etc. (signs of an allergic reaction related to treatment).
• Chronic kidney failure.
• Recurrence (reactivation) of hepatitis B virus infection if you have had hepatitis B in the past (a liver infection).

If you suffer from any of the above alterations, inform your doctor immediately.

Other adverse effects may include:

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

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

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

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

• Anorexia, weight loss, or altered sense of taste.

• Feeling of tiredness or weakness.
• Difficulty sleeping (insomnia).
• Tearing of the eyes with itching, redness, and swelling (conjunctivitis), watery eyes, or blurred vision.
• Nosebleeds.
• Pain or swelling in your abdomen, flatulence, heartburn, or constipation.
• Itching.
• Weakness or unusual hair loss.
• Numbness of the hands or feet.
• Ulcers in the mouth.
• 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 affect you significantly, consult your doctor.

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

• Painful red lumps on the skin, skin pain, redness of the skin (inflammation of the fatty tissue under the skin).
• Cough, secretion, or blockage in the nose, feeling of heaviness or pain when pressing the area around the eyes or nose, nasal congestion, sneezing, sore throat, with or without headache (signs of upper respiratory tract infection).
• Severe headache, like a stabbing pain or a throbbing sensation, usually on one side of the head, and 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, pain in the groin or pelvis, cloudy or reddish-brown urine (signs of urinary tract infection).
• Pain and swelling of the joints (signs of arthralgia).
• A constant feeling of sadness and loss of interest, which disrupts your ability to lead a normal life (signs of depression).
• A feeling of apprehension and concern along with physical symptoms such as palpitations, sweating, tremors, dry mouth (signs of anxiety).
• Drowsiness or excessive sleepiness.
• Tremors or involuntary movements (tremor).
• Memory impairment.
• Need to constantly move your legs (restless legs syndrome).
• Hearing noises (e.g., ringing, buzzing) in your ears that do not come from outside (tinnitus).
• High blood pressure (hypertension).
• Belching or gas.
• Inflammation of the lips.
• Difficulty swallowing.
• Increased sweating.
• Discoloration of the skin.
• Brittle nails.
• Reddish bumps or pimples around the hair root, possibly with pain, itching, or burning sensation (signs of inflammation of the hair follicles, also called folliculitis).
• Skin rash with peeling or flaking of the skin (exfoliative dermatitis).
• Breast growth (can occur in men or women).
• Dull pain and/or feeling of heaviness in the testicles or lower abdomen, pain when urinating, having sex, or ejaculating, blood in the urine (signs of testicular edema).
• Difficulty getting or maintaining an erection (erectile dysfunction).
• Heavy or irregular menstrual periods.
• Difficulty achieving or maintaining sexual arousal.
• Decreased sexual desire.
• Pain in the nipples.
• General feeling of discomfort (general malaise).
• Viral infections such as cold sores.
• Back pain in the lower part as a result of a 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 the 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 spasms and reduced consciousness (seizures)
• Discoloration of the nails.

Unknown frequency(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 a tingling sensation and burning pain.
• Painful skin lesions and/or blisters.
• Delayed growth in children and adolescents.

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

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting adverse effects, you can contribute to providing 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 expiration date stated on the carton after EXP. The expiration date is the last day of the month indicated.

This medicine does not require special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Dispose of the packaging and any unused medicine in the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Imatinib Krka d.d.

• The active ingredient is imatinib (as mesilate).

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

• The other ingredients are: tablet core: lactose monohydrate, cornstarch, 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 and Package Contents

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

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

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization 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

You can request more information about this medicine by contacting the local representative of the Marketing Authorization Holder:

KRKA Farmacéutica, S.L.,

C/ Anabel Segura 10, 28108

Alcobendas, Madrid,

Spain

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Date of the last revision of this leaflet: May 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/)