Sunitinib Krka

Package Leaflet: Information for the User

Sunitinib Krka, 12.5 mg, hard capsules

Sunitinib Krka, 25 mg, hard capsules

Sunitinib Krka, 50 mg, hard capsules

sunitinib

Read all of this leaflet carefully before 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 or pharmacist.
• 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 get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

• 1. What Sunitinib Krka is and what it is used for
• 2. Before you take 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 Sunitinib Krka is and what it is used for

Sunitinib Krka contains the active substance sunitinib, which is a protein kinase inhibitor.
Sunitinib Krka is used to treat cancer. It works by inhibiting the activity of certain proteins involved in the growth and spread of cancer cells.
Sunitinib Krka is used to treat the following types of cancer in adults:

• gastrointestinal stromal tumour (GIST), a type of stomach and intestine cancer, when imatinib (another anti-cancer medicine) 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 tumours (pNET), tumours that arise from hormone-producing cells in the pancreas, which 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, ask your doctor.

2 Before you take 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 taking Sunitinib Krka, tell your doctor:

• If you have high blood pressure. Sunitinib Krka may increase your blood pressure. Your doctor may check your blood pressure during treatment with Sunitinib Krka, and you may need to take medicines to lower your blood pressure.
• If you have or have had bleeding or blood clotting problems. Treatment with Sunitinib Krka may increase the risk of bleeding or changes in blood cell counts, which can lead to anaemia 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. Tell your doctor about any bleeding during treatment with Sunitinib Krka.
• If you have heart problems. Sunitinib Krka may cause heart problems. Tell your doctor if you feel very tired, have shortness of breath, or swelling in your feet and ankles.
• If you have irregular heartbeats. Sunitinib Krka may cause irregular heartbeats. During treatment with Sunitinib Krka, your doctor may perform an electrocardiogram to check for these irregularities. Tell your doctor if you experience dizziness, fainting, or irregular heartbeats during treatment with Sunitinib Krka.
• If you have recently had blood clots in your veins or arteries (types of blood vessels), including stroke, heart attack, embolism, or thrombosis. Tell 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 haemolytic anaemia (a condition where small blood vessels are damaged). 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. Tell your doctor if you feel very tired, are colder than usual, 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 take replacement thyroid hormone.
• If you have or have had pancreas or gallbladder problems. 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 gallbladder inflammation.
• If you have liver problems. Tell your doctor if you experience any of the following symptoms of liver problems: 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 your liver function before starting treatment with Sunitinib Krka, during treatment, and if you experience any symptoms.
• If you have kidney problems. 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 stopped 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, you may experience pyoderma gangrenosum (painful skin ulcers) or necrotizing fasciitis (a life-threatening infection of the skin and soft tissues). Tell your doctor immediately if you experience symptoms of infection around a skin wound, including fever, pain, redness, swelling, or discharge of pus or blood. These conditions usually resolve after stopping treatment with sunitinib. During treatment with sunitinib, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed, which initially appear as red patches with a target-like shape or round patches, often with centrally located blisters. The rash may progress to widespread blisters or peeling of the skin and may be life-threatening. If you experience a rash or the above-mentioned skin symptoms, tell your doctor immediately.
• If you have or have had seizures. Tell 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 the dose of anti-diabetic medicine needs to be adjusted to minimize the risk of low blood sugar. Tell 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

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, including those obtained without a prescription and those you plan to take.
Some medicines may affect the levels of Sunitinib Krka in your body. Tell 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

Do not drink grapefruit juice while taking Sunitinib Krka.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Women who may become pregnant should use effective contraception during treatment with Sunitinib Krka.
Do not breast-feed while taking Sunitinib Krka.

Driving and using machines

If you experience dizziness or extreme fatigue, 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 is essentially 'sodium-free'.

3 How to take Sunitinib Krka

Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor.
Your doctor will prescribe the dose that is right for you, depending on the type of cancer you have.
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

Do not push the Sunitinib Krka capsule through the blister foil, as this may damage the capsule. The capsules should be removed from the blister pack by peeling off the foil from the separate square of the blister pack.
To remove a capsule from the blister pack, follow these steps:

• 1. Hold the edge of the blister pack and separate one square of the blister pack 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 onto your hand.
• 4. Swallow the capsule whole.

If you take more Sunitinib Krka than you should

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

If you forget to take Sunitinib Krka

Do not take a double dose to make up for a forgotten dose.
If you have any further questions on the use of this product, ask your doctor or pharmacist.

4 Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if you experience any of the following side effects (see also section 2, "Before you take Sunitinib Krka"):

• heart problems. Tell your doctor if you feel very tired, have shortness of breath, or swelling in your 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. 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 travel to the lungs.
• kidney problems. Tell your doctor if you experience changes in urination frequency or inability to urinate, which may be symptoms of kidney failure.
• bleeding. 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, tarry stools; blood in urine; headache or changes in consciousness; coughing up blood or bloody sputum from the lungs or airways.
• tumour lysis syndrome leading to bowel perforation. 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 platelet count, 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, tooth pain, and/or jaw pain, mouth ulcers, inflammation, and/or dry mouth, taste disturbances, stomach upset, nausea, vomiting, diarrhoea, 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, excessive skin pigmentation, hair colour changes, palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome), 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 of severe infection (sepsis), which can lead to tissue damage, organ failure, and death
• decrease in blood sugar levels (see section 2, "Before you take Sunitinib Krka").
• protein loss in urine, sometimes causing swelling
• flu-like syndrome
• abnormal blood test results, including pancreas and liver enzymes
• high levels of uric acid in the blood
• haemorrhoids, anal pain, gum bleeding, difficulty swallowing, or loss of ability to swallow
• tongue pain, mouth inflammation, gastrointestinal inflammation, 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 disturbances, itching, skin peeling, and/or inflammation, blisters, acne, nail discoloration, hair loss
• skin sensation disturbances
• sensitivity disturbances, especially to touch
• heartburn
• dehydration
• hot flushes
• abnormal urine colour
• depression
• chills

Uncommon(may affect up to 1 in 100 people)

• life-threatening infection of soft tissues, including the perineal area (see section 2, "Before you take Sunitinib Krka").
• stroke
• heart attack caused by blockage or narrowing of the coronary arteries
• changes in heart rhythm or electrical activity.
• fluid accumulation around the heart (pericardial effusion)
• liver failure
• stomach pain caused by pancreatitis
• tumour lysis syndrome leading to bowel perforation
• inflammation of the gallbladder (with or without gallstones)
• formation of abnormal connections between one body cavity and another or with the skin
• mouth pain, tooth pain, and/or jaw pain, mouth ulcers, inflammation, and/or dry mouth. These may be symptoms of jawbone damage (osteonecrosis), see section 2, "Before you take Sunitinib Krka".
• excessive production of thyroid hormones leading to increased resting metabolism
• impaired wound healing after surgery
• increase in muscle enzyme activity (creatine phosphokinase) in the blood.
• excessive allergic reaction, including fever, skin rash, itching, hives, swelling of any part of the body, and difficulty breathing
• inflammation of the large intestine (colitis, ischaemic colitis)

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

• severe skin reaction (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme)
• tumour lysis syndrome, 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 inflammation
• damage to small blood vessels called microangiopathic haemolytic anaemia

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

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

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Side effects can be reported to the national reporting system via the Medicines Agency website or directly to the manufacturer. By reporting side effects, you can help provide more information on the safety of this medicine.

5 How to store Sunitinib Krka

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton, bottle, and blister after EXP. The expiry date refers to the last day of that month.
Store in the original package to protect from moisture.
There are no special storage instructions 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. Ask your pharmacist how to dispose of medicines no longer required. 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 shell with a white printing ink imprint: "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 shell with an orange body, with a white printing ink imprint: "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 shell with a caramel (light brown) body, with a black printing ink imprint: "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, containing 30 hard capsules, 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 Authorisation Holder and Manufacturer

Marketing Authorisation 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 on this medicine, contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa
Tel. 22 57 37 500

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

Date of last revision of the leaflet:13.08.2024