Sunitinib Krka

Leaflet accompanying the packaging: information for the user

Sunitinib Krka, 12.5 mg, hard capsules

Sunitinib Krka, 25 mg, hard capsules

Sunitinib Krka, 50 mg, hard capsules

Sunitinib

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any further questions, you should ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, you should tell your doctor. See section 4.

Table of contents of the leaflet

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

1 What is Sunitinib Krka and what is it used for

Sunitinib Krka contains the active substance sunitinib, which is a protein kinase inhibitor.
Sunitinib Krka is used to treat cancers. It inhibits the activity of a specific group of proteins,
known to be involved in the growth and spread of cancer cells.
Sunitinib Krka is used to treat the following types of cancer in adults:

• gastrointestinal stromal tumors (GISTs), a type of stomach and intestine cancer, when imatinib (another anticancer drug) has stopped working or the patient cannot take it;
• metastatic renal cell carcinoma (MRCC), a type of kidney cancer that has spread to other parts of the body;
• pancreatic neuroendocrine tumors (pNETs) (tumors that arise from hormone-producing cells in the pancreas) that are progressing or cannot be surgically removed.

If you have any questions about how Sunitinib Krka works or why it has been prescribed for you, you should ask your doctor.

2 Important information before taking Sunitinib Krka

When not to take Sunitinib Krka

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

Warnings and precautions

Before starting treatment with Sunitinib Krka, you should discuss with your doctor:

• If you have high blood pressure. Sunitinib Krka may increase blood pressure. Your doctor may check your blood pressure during treatment with Sunitinib Krka, and you may need to be treated with blood pressure-lowering medicines.
• If you have or have had blood disorders, bleeding, or bruising. Treatment with Sunitinib Krka may increase the risk of bleeding or changes in the number of certain blood cells, which can cause anemia or affect the blood's ability to clot. If you are taking warfarin or acenocoumarol, blood-thinning medicines used to prevent blood clots, there may be a higher risk of bleeding. You should tell your doctor about any bleeding during treatment with Sunitinib Krka.
• If you have heart problems. Sunitinib Krka may cause heart problems. You should tell your doctor if you experience extreme fatigue, shortness of breath, or swelling of the feet or ankles.
• If you have heart rhythm disorders. Sunitinib Krka may cause abnormal heart rhythms. During treatment with Sunitinib Krka, your doctor may perform an electrocardiogram to assess these disorders. You should tell your doctor if you experience dizziness, fainting, or abnormal heart rhythms during treatment with Sunitinib Krka.
• If you have recently had blood clots in the veins and/or arteries (types of blood vessels), including stroke, heart attack, embolism, or thrombosis. You should contact your doctor immediately if you experience symptoms such as chest pain or tightness, arm, back, neck, or jaw pain, shortness of breath, numbness or weakness on one side of the body, difficulty speaking, headache, or dizziness.
• If you have or have had an aneurysm (enlargement and weakening of the wall of a blood vessel) or a tear in the wall of a blood vessel.
• If you have or have had microangiopathic hemolytic anemia (a condition characterized by the destruction of red blood cells). You should tell your doctor if you experience fever, fatigue, weakness, bruising, bleeding, swelling, confusion, loss of vision, or seizures.
• If you have thyroid problems. Sunitinib Krka may cause thyroid problems. You should tell your doctor if you experience extreme fatigue, feel colder than others, or have a hoarse voice during treatment with Sunitinib Krka. Your doctor should check your thyroid function before starting treatment with Sunitinib Krka and regularly during treatment. If your thyroid does not produce enough thyroid hormone, you may need to be treated with replacement thyroid hormone.
• If you have or have had pancreatic or gallbladder disorders. You should tell your doctor if you experience any of the following symptoms: stomach pain (upper abdomen), nausea, vomiting, and fever. These may be symptoms of pancreatitis or cholecystitis.
• If you have or have had liver disease. You should inform your doctor if you experience any of the following symptoms of liver dysfunction during treatment with Sunitinib Krka: itching, yellowing of the eyes or skin, dark urine, or pain or discomfort in the right upper abdomen. Your doctor should perform blood tests to check liver function before starting treatment with Sunitinib Krka, during treatment, and if there are clinical signs.
• If you have or have had kidney disease. Your doctor will monitor your kidney function.
• If you are going to have surgery or have recently had surgery. Sunitinib Krka may affect wound healing. Sunitinib Krka is usually discontinued in patients before surgery. Your doctor will decide when to restart Sunitinib Krka.
• You are advised to have a dental check-up before starting treatment with Sunitinib Krka:
• If you have or have had skin and subcutaneous tissue disorders. During treatment with this medicine, pyoderma gangrenosum (painful skin ulcers) or necrotizing fasciitis (a rapidly spreading infection of the skin and/or soft tissues that can be life-threatening) may occur. You should contact your doctor immediately if you experience symptoms of infection around skin damage, including fever, pain, redness, swelling, or discharge of pus or blood. These disorders usually resolve after discontinuation of sunitinib treatment. During sunitinib treatment, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed, which initially appear as reddened patches with a target-like shape or round patches, often with centrally located blisters. The rash can transform into widespread blisters or skin peeling and can be life-threatening. If you experience a rash or the above-mentioned skin symptoms, you should contact your doctor immediately.
• If you have or have had seizures. You should inform your doctor as soon as possible if you experience high blood pressure, headache, or loss of vision.
• If you have diabetes. In patients with diabetes, blood sugar levels should be regularly checked to assess whether it is necessary to adjust the dose of the anti-diabetic medicine to minimize the risk of low blood sugar. You should inform your doctor as soon as possible if you experience symptoms related to low blood sugar (fatigue, palpitations, excessive sweating, hunger, and loss of consciousness).

Children and adolescents

Sunitinib Krka is not recommended for use in children and adolescents under 18 years of age.

Sunitinib Krka and other medicines

You should tell your doctor or pharmacist about all medicines you are taking or have recently taken, including those obtained without a prescription, as well as any medicines you plan to take.
Some medicines may affect the levels of Sunitinib Krka in your body. You should inform your doctor if you are taking medicines containing the following active substances:

• ketokonazole, itraconazole - used to treat fungal infections
• erythromycin, clarithromycin, rifampicin - used to treat infections
• ritonavir - used to treat HIV infections
• dexamethasone - a corticosteroid used in various diseases (such as allergic disorders and/or respiratory disorders or skin diseases)
• phenytoin, carbamazepine, phenobarbital - used to treat epilepsy and other neurological conditions,
• herbal products containing St. John's Wort (Hypericum perforatum) - used to treat depression and anxiety disorders.

Taking Sunitinib Krka with food and drink

During treatment with Sunitinib Krka, you should not drink grapefruit juice.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, you should ask your doctor or pharmacist for advice before taking this medicine.
Women who can become pregnant should use effective contraception during treatment with Sunitinib Krka.
Women who are breastfeeding should inform their doctor. You should not breastfeed while taking Sunitinib Krka.

Driving and using machines

If you experience dizziness or extreme fatigue, you should be careful when driving or operating machinery.

Sunitinib Krka contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per capsule, which means it is essentially 'sodium-free'.

3 How to take Sunitinib Krka

You should always take this medicine exactly as your doctor has told you.
If you are not sure, you should ask your doctor.
Your doctor will prescribe the dose that is right for you, depending on the type of cancer.
For patients being treated for:

• GIST or MRCC: the usual dose is 50 mg taken once a day for 28 days (4 weeks), followed by a 14-day (2-week) break (without treatment), in 6-week treatment cycles.
• pNET: the usual dose is 37.5 mg taken once a day continuously.

Your doctor will determine the correct dose for you and when to stop treatment with Sunitinib Krka.
Sunitinib Krka can be taken with or without food.

Taking this medicine

Sunitinib Krka capsules should not be pushed through the blister foil, as this may damage them. The capsules should be removed by peeling off the blister foil from the separate square of the blister.
To remove a capsule from the blister, you should:

• 1. Hold the edge of the blister and separate one square of the blister by gently bending and tearing it at the perforation.
• 2. Pull the marked edge of the foil and completely remove it.

• 3. Shake the capsule into your hand.
• 4. Swallow the capsule whole.

Taking a higher dose of Sunitinib Krka than prescribed

If you have taken too many capsules, you should contact your doctor immediately.
Medical attention may be necessary.

Missing a dose of Sunitinib Krka

You should not take a double dose to make up for a missed dose.
If you have any further questions about taking this medicine, you should ask your doctor or pharmacist.

4 Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You should contact your doctor immediately if you experience any of the following side effects (see also section 2, "Important information before taking Sunitinib Krka"):

• heart problems. You should tell your doctor if you feel extremely tired, experience shortness of breath, or have swelling of the feet and ankles. These may be symptoms of heart problems, which can include heart failure and problems with the heart muscle (cardiomyopathy).
• lung problems or difficulty breathing. You should tell your doctor if you experience coughing, chest pain, sudden shortness of breath, or coughing up blood. These may be symptoms of a condition called pulmonary embolism, which occurs when blood clots move to the lungs.
• kidney problems. You should tell your doctor if you experience changes in urination frequency or inability to urinate, which can be a sign of kidney failure.
• bleeding. You should tell your doctor if you experience any of the following symptoms or severe bleeding during treatment with Sunitinib Krka: stomach pain and swelling; vomiting blood; black and tarry stools; blood in urine; headache or changes in consciousness; coughing up blood or bloody sputum from the lungs or airways.
• tumor lysis syndrome leading to intestinal perforation. You should tell your doctor if you experience severe stomach pain, fever, nausea, vomiting, blood in stool, or changes in bowel movements.

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

• decrease in the number of platelets, red blood cells, and/or white blood cells (e.g., neutrophils)
• shortness of breath
• high blood pressure
• extreme fatigue, loss of strength
• swelling caused by fluid accumulation under the skin and around the eyes, allergic rash, deep
• mouth pain and/or mouth ulcers, painful mouth sores, and/or inflammation, and/or dry mouth, taste disturbances, stomach disorders, nausea, vomiting, diarrhea, constipation, abdominal pain and/or swelling, loss of and/or decreased appetite
• decrease in thyroid hormone production (hypothyroidism)
• dizziness
• headache
• nosebleeds
• back pain, joint pain
• arm and leg pain
• yellowing of the skin and/or discoloration, skin thickening, hair color changes, palmar-plantar erythrodysesthesia, rash, dry skin
• cough
• fever
• difficulty sleeping

Common(may affect up to 1 in 10 people)

• blood clots in blood vessels
• insufficient blood supply to the heart due to blockage or narrowing of the coronary arteries
• chest pain
• decrease in the amount of blood pumped by the heart
• fluid accumulation, including in the lungs
• infections
• complication after severe infection (sepsis), which can lead to tissue damage, organ failure, and death
• decrease in blood sugar levels (see section 2, "Important information before taking Sunitinib Krka").
• protein loss in urine, sometimes causing swelling
• flu-like syndrome
• abnormal blood test results, including pancreatic and liver enzymes
• high levels of uric acid in the blood
• hemorrhoids, anal pain, gum bleeding, difficulty swallowing, or loss of swallowing ability
• tongue pain or burning sensation, inflammation of the mucous membranes, excessive gas in the stomach or intestines
• weight loss
• musculoskeletal pain (muscle and bone pain), muscle weakness, fatigue, muscle cramps
• dryness of the nasal mucosa, feeling of nasal congestion
• excessive tearing
• skin sensation disorders, itching, skin peeling, and/or inflammation, blisters, acne, nail discoloration, hair loss
• limb sensation disorders
• disorders related to increased or decreased sensitivity, especially to touch
• heartburn
• dehydration
• hot flashes
• abnormal urine color
• depression
• chills

Uncommon(may affect up to 1 in 100 people)

• life-threatening infection of soft tissues, including the perianal and genital area (see section 2, "Important information before taking Sunitinib Krka").
• stroke
• heart attack caused by interruption or reduction of blood supply to the heart
• changes in heart electrical activity or rhythm disorders.
• fluid accumulation around the heart (pericardial effusion)
• liver failure
• stomach pain (abdominal pain) caused by pancreatitis
• tumor lysis syndrome leading to intestinal perforation
• inflammation (swelling or redness) of the gallbladder with or without gallstones
• formation of abnormal connections between one body cavity and another or with the skin
• mouth pain, toothache, and/or jaw pain, swelling, or mouth ulcers, numbness, or a feeling of heaviness in the jaw, or tooth mobility. These may be symptoms of jawbone damage (osteonecrosis), see section 2, "Important information before taking Sunitinib Krka".
• excessive production of thyroid hormones leading to increased resting metabolism
• impaired wound healing after surgery
• increased activity of the muscle enzyme (creatine phosphokinase) in the blood.
• excessive allergic reaction, including hay fever, skin rash, itching, hives, swelling of any part of the body, and difficulty breathing
• inflammation of the large intestine (colitis, ischemic colitis)

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

• severe skin reaction (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme)
• tumor lysis syndrome, which is a group of metabolic complications that can occur during cancer treatment. These complications are caused by the breakdown products of dying cancer cells and can include nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, and changes in laboratory test results (high levels of potassium, uric acid, and phosphorus, and low levels of calcium in the blood), which can lead to kidney damage and acute kidney failure.
• abnormal muscle breakdown, which can cause kidney disease (rhabdomyolysis).
• abnormal brain changes, which can cause a syndrome of symptoms including headache, confusion, seizures, and loss of vision (reversible posterior leukoencephalopathy syndrome)
• painful skin ulcers (pyoderma gangrenosum)
• liver inflammation
• thyroid gland inflammation
• damage to the smallest blood vessels called microangiopathic hemolytic anemia

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

• enlargement and weakening of the wall of a blood vessel or rupture of the wall of a blood vessel (aneurysm and arterial dissection)
• lack of energy, confusion, drowsiness, loss of consciousness, or coma - these symptoms may be signs of the toxic effect of high blood ammonia levels on the brain (hyperammonemic encephalopathy).

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, you should tell your doctor. You can also report side effects directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. You can also report side effects to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5 How to store Sunitinib Krka

The medicine should be kept out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, container, and blister after EXP. The expiry date refers to the last day of that month.
Store in the original packaging to protect from moisture.
There are no special storage temperature requirements for this medicine.
Do not use this medicine if you notice that the packaging is damaged or if there are signs of previous attempts to open it.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6 Contents of the pack and other information

What Sunitinib Krka contains

Sunitinib Krka 12.5 mg hard capsules
The active substance is sunitinib. Each hard capsule contains sunitinib malate equivalent to 12.5 mg of sunitinib.
The other ingredients are:

• Capsule content:povidone K30 LP, microcrystalline cellulose, sodium croscarmellose (see section 2, "Sunitinib Krka contains sodium"), magnesium stearate;
• Capsule shell:gelatin, titanium dioxide (E 171), iron oxide red (E 172), iron oxide yellow (E 172).
• Printing ink:shellac, titanium dioxide (E 171), propylene glycol.

Sunitinib Krka 25 mg hard capsules
The active substance is sunitinib. Each hard capsule contains sunitinib malate equivalent to 25 mg of sunitinib.
The other ingredients are:

• Capsule content:povidone K30 LP, microcrystalline cellulose, sodium croscarmellose (see section 2, "Sunitinib Krka contains sodium"), magnesium stearate;
• Capsule shell:gelatin, titanium dioxide (E 171), iron oxide red (E 172), iron oxide yellow (E 172), iron oxide black (E 172).
• Printing ink:shellac, titanium dioxide (E 171), propylene glycol.

Sunitinib Krka 50 mg hard capsules
The active substance is sunitinib. Each hard capsule contains sunitinib malate equivalent to 50 mg of sunitinib.
The other ingredients are:

• Capsule content:povidone K30 LP, microcrystalline cellulose, sodium croscarmellose (see section 2, "Sunitinib Krka contains sodium"), magnesium stearate;
• Capsule shell:gelatin, titanium dioxide (E 171), iron oxide red (E 172), iron oxide yellow (E 172), iron oxide black (E 172).
• Printing ink:shellac, iron oxide black (E 172), propylene glycol

What Sunitinib Krka looks like and contents of the pack

Sunitinib Krka 12.5 mg hard capsules
Sunitinib Krka 12.5 mg: orange capsule with a white inscription "SNB" and "12.5" on the body.
The capsule is filled with an orange powder. Capsule size: 4 (length approximately 14 mm).
Sunitinib Krka 25 mg hard capsules
Sunitinib Krka 25 mg: caramel (light brown) capsule with a white inscription "SNB" and "25" on the body.
The capsule is filled with an orange powder. Capsule size: 3 (length approximately 16 mm).
Sunitinib Krka 50 mg hard capsules
Sunitinib Krka 50 mg: caramel (light brown) capsule with a black inscription "SNB" and "50" on the body.
The capsule is filled with an orange powder. Capsule size: 1EL (elongated; length approximately 20 mm).
The medicine is available in HDPE bottles with a PP child-resistant closure, with a desiccant, containing 30 hard capsules, in a cardboard box, and in single-dose blisters with a desiccant, containing 7 x 1, 10 x 1, 14 x 1, 20 x 1, 21 x 1, 28 x 1, or 30 x 1 hard capsules, in a cardboard box.
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:
Synthon BV, Microweg 22, 6545CM Nijmegen, Netherlands
Synthon Hispania S.L., Calle De Castello 1, 08830 Sant Boi de Llobregat, Barcelona, Spain
Synthon s.r.o., Brnĕnská 32/čp. 597, 678 01 Blansko, Czech Republic
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
KRKA – FARMA d.o.o., V. Holjevca 20/E, 10450 Jastrebarsko, Croatia
For further information about this medicine, you should contact the local representative of the marketing authorization holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warsaw
Tel. 22 57 37 500

This medicine is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of the leaflet:13.08.2024