Package Leaflet: Information for the Patient

Imatinib Krka d.d. 400 mg Film-Coated TabletsEFG

Read this leaflet carefully before you start 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 questions, ask your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only. Do not pass it on to others even if they have the same symptoms as you, as it may harm them.

-If you experience any side effects, talk to your doctor, pharmacist or nurse. See section 4.

Imatinib Krka d.d. is a medication that contains an active ingredient called imatinib. This medication acts by inhibiting the growth of abnormal cells in the following diseases, which 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 form of leukemia in which certain abnormal white blood cells (called myeloid cells) start to grow uncontrollably.

• Acute Lymphoblastic Leukemia with Philadelphia chromosome positive (ALL Ph-positive).Leukemia is a cancer of the white blood cells. These white blood cells normally help the body fight infections.Acute lymphoblastic leukemia is a form of leukemia in which abnormal white blood cells (called lymphoblasts) start to grow uncontrollably. Imatinib inhibits the growth of these cells.

Imatinib is also a treatment for adults for:

• Myeloproliferative/Myelodysplastic Syndromes (MPN/ MDS).These are a group of blood diseases in which some blood cells start to grow uncontrollably. 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 blood diseases in which some blood cells (called eosinophils) start to grow uncontrollably. Imatinib inhibits the growth of these cells in a certain subtype of these diseases.
• Gastrointestinal Stromal Tumors (GIST). GIST is a cancer of the stomach and intestine. It originates from an uncontrolled growth of the supporting tissue of these organs.

• Dermatofibrosarcoma Protuberans (DFSP).DFSP is a cancer of the tissue under the skin in which some cells start to grow uncontrollably. Imatinib inhibits the growth of these cells.

In the rest of this prospectus, abbreviations will be used when referring to these diseases.

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

Only a doctor with experience in treating blood cell cancers or solid tumors will prescribe Imatinib Krka d.d.

Follow your doctor's instructions carefully, even if they differ from the general information in this leaflet.

Do not take Imatinib Krka d.d.

• if you are allergic to imatinib or any of the other components of this medication (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, ask your doctor for advice.

Warnings and precautions

Consult 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 medication levotiroxine because your thyroid has been removed.

• if you have ever had or may have a hepatitis B infection at present. This is because Imatinib Krka d.d. could make hepatitis B become active again, which can be fatal in some cases. Your doctor will carefully check 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 a blood vessel damage called microangiopathic thrombosis (MAT).

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

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

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

While taking Imatinib Krka d.d., your doctor will regularly check if the medication is working. Blood tests and regular weighing will also be performed.

Children and adolescents

Imatinib Krka d.d. is also a treatment for children and adolescents with LMC. There is no experience in children with LMC under 2 years of age. Experience in children and adolescents with Ph-positive CML is limited, and experience in children and adolescents with SMD/SMP, DFSP, and SHE/LEC is very limited.

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

Other medications and Imatinib Krka d.d.

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including over-the-counter medications (such as paracetamol) and herbal medicines (such as St. John's Wort). Some medications 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 side effects or making Imatinib Krka d.d. less effective. Imatinib Krka d.d. may also produce the same effect in other medications.

Inform your doctor if you are using medications that prevent blood clotting.

Pregnancy, breastfeeding, and fertility

-If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication.

-It is not recommended to use Imatinib Krka d.d. during pregnancy except when clearly necessary, as it may harm your baby. Your doctor will discuss the possible risks of taking Imatinib Krka d.d. during pregnancy with you.

-Women who may become pregnant are advised to use an effective contraceptive method during treatmentand for 15days after completing treatment..

-Do not breastfeed your baby during treatment with Imatinib Krka d.d.or for the following 15 days after completing treatment, as it may harm your baby..

-Patients concerned about their fertility while taking Imatinib Krka d.d. should consult their doctor.

Driving and operating machines

You may experience dizziness, drowsiness, or blurred vision while taking this medication. If this happens, do not drive or operate tools or machines until you feel better again.

Imatinib Krka d.d. contains lactose

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

Your doctor has prescribed this medicine because you have a serious disease. Imatinib may help you fight this disease.

However, follow exactly the administration instructions for this medicine indicated by your doctor or pharmacist. It is essential that you do it for the time your doctor or pharmacist indicates. In case of doubt, consult your doctor or pharmacist again.

Do not stop taking this medicine unless your doctor tells you to. If you cannot take the medicine as prescribed by your doctor or think you do not need to take it for a longer time, contact your doctor immediately.

How much Imatinib Krka d.d. to take

Use in adults

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

If you are being treated for LMC:

The starting dose is 400 mg or 600 mg, depending on your situation:

-400 mgwhich should be taken as a 400 mg tabletonceper day.

-600 mgwhich should be taken as a 400 mg tablet plus 2 100 mg tabletsonceper day.

If you are being treated for GIST:

The initial dose is 400 mg which should be taken as a 400 mg tablet once per day.

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

If you are being treated for LLA Ph-positive:

The starting dose is 600 mg which is taken as a 400 mg tablet plus 2 100 mg tabletsonceper day.

If you are being treated for SMD/SMP:

The starting dose is 400 mg which is taken as a tabletonceper day.

If you are being treated for SHE/LEC:

The starting dose is 100 mg which is taken as a 100 mg tabletonceper day.

Your doctor may decide to increase the dose to 400 mg which is taken as a 400 mg tabletonceper day, depending on how you respond to treatment.

If you are being treated for DFSP:

The dose is 800 mg per day (2 400 mg tablets) which should be taken one tablet in the morning and one tablet in the evening.

Use in children and adolescents

Your doctor will tell you how many tablets of imatinib to administer to the child. The amount of imatinib administered will depend on the child's situation, weight, and height. The total daily dose in children and adolescents with LMC should not exceed 800 mg or 600 mg in LLA-Ph positive. 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 mineral water or still water or apple juice:

• Use about 50 ml for each 100 mg tablet.
• Use about 200 ml for each 400 mg tablet.
• Stir until the tablets have completely dissolved.
• Once the tablet has dissolved, drink the entire contents of the glass immediately. There may be remnants of the dissolved tablets in the glass.

For how long to take Imatinib Krka d.d.

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

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

If you have accidentally taken too many tablets, talk to your doctorimmediately. You may need medical attention. Bring the medicine packaging.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 915620420, indicating the medicine and the amount ingested.

If you forgot 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 the normal schedule.
• Do not take a double dose to compensate for the missed doses.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

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

Some side effects can be serious. Inform your doctor immediately if you experience any of the following:

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

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

• Pale skin, feeling tired, difficulty breathing, dark urine (signs of low red blood cell count).
• Eye pain or vision problems, bleeding in the eyes.
• Bone or joint pain (signs of osteonecrosis).
• Blisters on the skin or mucous membranes (signs of pemphigus).
• Hip or walking difficulty.
• Numbness or cold sensation in your feet and toes (signs of Raynaud's syndrome).
• Sudden swelling and redness of the skin (sign of a skin infection called cellulitis).
• Difficulty hearing.
• Weakness and muscle spasms, abnormal heart rhythm (signs of changes in potassium levels in the blood).
• Bruises.
• Stomach pain with nausea.
• Muscle spasms with fever, reddish-brown urine, muscle pain or weakness (signs of muscle problems).
• Abdominal pain, unexpected vaginal bleeding, dizziness or fainting due to low blood pressure (signs of ovarian or uterine problems).
• Nausea, difficulty breathing, irregular heartbeat, cloudy urine, fatigue, and/or joint pain associated with abnormal laboratory test results (e.g., elevated potassium, uric acid, and calcium levels, and low phosphorus levels in the blood).

• Microangiopathic thrombosis (blood clots in small blood vessels).

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

• Combination of widespread intense rash, feeling unwell, fever, elevated white blood cell count, or yellow skin or eyes (signs of jaundice) with difficulty breathing, chest pain, decreased urine output, and feeling thirsty, etc. (signs of an allergic reaction related to treatment).
• Chronic kidney failure.
• Reactivation of hepatitis B infection if you have had hepatitis B in the past (a liver infection).

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

Other side effects may include:

Very common side effects(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 imatinib treatment or when stopping imatinib treatment.
• Inflammations such as swollen ankles or eyes.
• Weight gain.

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

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

• Loss of appetite, weight loss, or altered sense of taste.

• Feeling tired or weak.
• Difficulty sleeping (insomnia).
• Excessive tearing of the eyes with itching, redness, and swelling (conjunctivitis), watery eyes, or blurry vision.
• Nasal bleeding.
• Abdominal pain, bloating, heartburn, or constipation.
• Itching.
• Unusual hair loss or weakness.
• Numbness in your 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 affect you significantly,consult your doctor.

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

• Red, painful bumps on the skin, skin pain, skin redness (inflammation of subcutaneous fat).
• Cough, nasal secretion or blockage, feeling of pressure or pain in 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 or pulsating pain, usually on one side of the head, often accompanied by nausea, vomiting, and sensitivity to light or sound (signs of migraine).
• Flu-like symptoms.
• Pain or burning sensation while urinating, fever, pain in the groin or pelvis, cloudy or reddish-brown urine (signs of urinary tract infection).
• Joint pain (signs of arthralgia).
• Feeling of sadness and loss of interest, which interferes with normal life (signs of depression).
• Feeling of anxiety and concern, accompanied by physical symptoms such as palpitations, sweating, tremors, dry mouth (signs of anxiety).
• Drowsiness, excessive sleepiness, or excessive sleep.
• Tremors or involuntary movements (tremor).
• Memory damage.
• Need to constantly move your legs (restless legs syndrome).
• Heard sounds (e.g., bells, buzzing) in your ears that do not come from outside (tinnitus).
• High blood pressure (hypertension).
• Belching or gas.
• Lip inflammation.
• Difficulty swallowing.
• Increased sweating.
• Skin discoloration.
• Brittle nails.
• Red, itchy, or painful bumps around the hair follicles, possibly with pain, itching, or burning sensation (signs of folliculitis).
• Peeling skin rash (dermatitis exfoliativa).
• Breast growth (may occur in men or women).
• Dull, aching pain or feeling of pressure in the testicles or lower abdomen, pain while urinating, during sex, or ejaculation, blood in the urine (signs of testicular edema).
• Inability to achieve or maintain an erection (erectile dysfunction).
• Intense or irregular menstrual periods.
• Difficulty achieving or maintaining sexual excitement.
• Decreased sex drive.
• Nipple pain.
• General feeling of discomfort (general malaise).
• Herpes labialis (cold sores).
• 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, acid reflux, feeling full, bloating, black stool (signs of stomach ulcer).
• Joint or muscle stiffness.
• Abnormal laboratory test results.

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

Rare side effects(may affect up to 1 in 1,000 people):

• Confusion.
• Seizure episode with reduced consciousness (convulsions)
• Yellowing 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 sensation.
• Painful skin lesions with blisters.
• Delayed growth in children and adolescents.

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box after CAD. The expiration date is the last day of the month indicated.

This medication does not require special conditions for conservation.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition of Imatinib Krka d.d.

• The active ingredient is imatinib (as mesylate).

Each film-coated tablet contains 400 mg of imatinib (as mesylate).

• The other components are: nucleus of the tablet : lactose monohydrate, cornstarch, hydroxypropylcellulose, microcrystalline cellulose (E460), crospovidone, colloidal anhydrous silica, magnesium stearate (E470b); coating: polyvinyl alcohol, titanium dioxide (E171), macrogol, talc, iron oxide red (E172), iron oxide yellow (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 (dimensions: 22 mm x 9 mm), biconvex.

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

Only some pack sizes may be marketed.

Marketing authorization holder and responsible person for manufacturing

Marketing authorization holder:

KRKA, d.d.,

Novo mesto, Šmarješka cesta 6,

8501 Novo mesto,

Slovenia

Responsible person for manufacturing:

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.,

V. Holjevca 20/E,

10450 Jastrebarsko,

Croatia

You can obtain further information about this medicinal product by contacting the local representative of the marketing authorization holder:

KRKA Farmacéutica, S.L.,

C/ Anabel Segura 10, 28108

Alcobendas, Madrid,

Spain

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

Last update of the summary of product characteristics: May 2024

The detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) ( http://www.aemps.gob.es/ )