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
Please 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 symptoms are the same as yours.
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Sunitinib Krka is and what it is used for
2. What you need to know 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 blocks the activity of a special 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 tumours (GIST), a type of stomach and intestinal tumour, when imatinib (another anticancer medicine) has stopped working or cannot be used;
• Metastatic renal cell carcinoma (MRCC), a type of kidney cancer that has spread to other parts of the body;
• Pancreatic neuroendocrine tumours (pNET) (tumours arising 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 this medicine has been prescribed,
ask your doctor.
2 What you need to know before you take Sunitinib Krka
Do not 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
Talk to your doctor before taking Sunitinib Krka:

• If you have high blood pressure. Sunitinib Krka may increase blood pressure. Your doctor may monitor your blood pressure during treatment with Sunitinib Krka, and you may be treated with blood pressure-lowering medicines if necessary.
• If you have or have had blood disorders, bleeding or bruising. Treatment with Sunitinib Krka may increase the risk of bleeding or may change the number of certain blood cells, which may cause anaemia or affect the blood’s ability to clot. If you are taking warfarin or acenocoumarol, anticoagulant medicines used to prevent blood clots, there may be an increased 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 experience extreme tiredness, shortness of breath, or swelling of the feet or ankles.
• If you have heart rhythm disorders. Sunitinib Krka may cause an irregular heartbeat. Your doctor may perform an electrocardiogram during treatment with Sunitinib Krka to assess these disorders. Tell your doctor if you experience dizziness, fainting, or an irregular heartbeat while taking Sunitinib Krka.
• If you have recently had blood clots in your veins and/or arteries (types of blood vessels), including stroke, heart attack, embolism, or thrombosis. Contact your doctor immediately if you experience symptoms such as chest pain or tightness, pain in the arms, back, neck, or jaw, shortness of breath, numbness or weakness on one side of the body, difficulty speaking, headache, or dizziness while taking Sunitinib Krka.
• If you have or have had an aneurysm (a bulge and weakening of a blood vessel wall) or a tear in the wall of a blood vessel.
• If you have or have had damage to the smallest blood vessels called thrombotic microangiopathy. Tell your doctor if you experience fever, tiredness, fatigue, bruising, bleeding, swelling, confusion, vision loss, or seizures.
• If you have or have had thyroid problems. Sunitinib Krka may cause thyroid problems. Tell your doctor if you feel unusually tired, feel colder than others, or have a hoarse voice while taking Sunitinib Krka. Your doctor should check your thyroid function before starting Sunitinib Krka and regularly during treatment. If your thyroid does not produce enough thyroid hormone, you may be treated with thyroid hormone replacement.
• 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 signs of pancreatitis or gallbladder inflammation.
• If you have or have had liver problems. Inform your doctor if you experience any of the following signs of liver problems while taking Sunitinib Krka: itching, yellowing of the eyes or skin, dark-coloured urine, or pain or discomfort in the upper right abdomen. Your doctor should order blood tests to check liver function before starting Sunitinib Krka, during treatment, and if clinically indicated.
• If you have or have had kidney problems. Your doctor will monitor kidney function.
• If you are scheduled for surgery or have recently undergone surgery. Sunitinib Krka may affect wound healing. Sunitinib Krka is usually stopped 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 develop mouth pain, tooth or jaw pain, swelling or ulceration of the mouth, numbness or heaviness in the jaw, or loose teeth, inform your oncologist and dentist immediately.
• if you require invasive dental treatment or oral surgery, inform your dentist that you are taking Sunitinib Krka, especially if you are also taking or have taken intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone problems, which may be taken for another condition.
• If you have or have had skin and subcutaneous tissue disorders. While taking this medicine, pyoderma gangrenosum (painful skin ulceration) or necrotising fasciitis (a rapidly spreading infection of the skin and/or soft tissues that may be life-threatening) may occur. Contact your doctor immediately if you experience signs of infection around a skin injury, including fever, pain, redness, swelling, or pus or blood discharge. These conditions usually resolve after stopping sunitinib treatment. Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed during sunitinib treatment. These initially appear as red, target-shaped or circular spots, often with centrally located blisters. The rash may progress to widespread blistering or skin peeling and may be life-threatening. If you develop a rash or the above-mentioned skin symptoms, contact your doctor immediately.
• If you have or have had seizures. Inform your doctor as soon as possible if you experience high blood pressure, headache, or vision loss.
• If you have diabetes. Blood sugar levels should be monitored regularly in patients with diabetes to assess whether adjustment of antidiabetic medication is needed to minimise the risk of low blood sugar. Inform your doctor as soon as possible if you experience symptoms of low blood sugar (tiredness, rapid heartbeat, excessive sweating, hunger, or loss of consciousness).

Children and adolescents
Sunitinib Krka is not recommended for use in individuals under 18 years of age.
Sunitinib Krka with other medicines
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines, including those obtained without a prescription, as well as herbal supplements or
medicines you plan to take.
Some medicines may affect the concentration of Sunitinib Krka in your body. Inform your doctor if
you are taking medicines containing any of the following active substances:

• ketoconazole, itraconazole – used to treat fungal infections
• erythromycin, clarithromycin, rifampicin – used to treat infections
• ritonavir – used to treat HIV infection
• dexamethasone – a corticosteroid used for various conditions (such as allergic 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.

Taking Sunitinib Krka with food and drink
Do not drink grapefruit juice while taking Sunitinib Krka.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby,
you should consult your doctor or pharmacist before using this medicine.
Women who could become pregnant should use effective contraception during treatment with
Sunitinib Krka.
Breastfeeding women should inform their doctor. Do not breastfeed while taking Sunitinib Krka.
Driving and using machines
If you experience dizziness or extreme tiredness, exercise caution when driving or operating
machinery.
Sunitinib Krka contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. it is considered “sodium-free”.
3 How to take Sunitinib Krka
Always take this medicine exactly as your doctor has told you. Ask your doctor if you are not sure.
Your doctor will prescribe the dose appropriate for you, depending on the type of cancer.
For patients being treated for:

• GIST or MRCC: the usual dose is 50 mg taken once daily for 28 days (4 weeks), followed by a 14-day (2-week) break (no medicine), in 6-week treatment cycles.
• pNET: the usual dose is 37.5 mg taken once daily continuously.

Your doctor will determine the appropriate 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 capsules out of the blister foil, as this may damage them. Capsules should be removed by peeling back the foil from the individual blister square. To remove a capsule from the blister, follow these steps:

1. Hold the edge of the blister and separate one blister square by gently bending and tearing at the perforation.
2. Pull the marked edge of the foil and completely peel it back.
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 intervention may be
necessary.
If you forget to take Sunitinib Krka
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 or pharmacist.
4 Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if you experience any of the following side effects (see also
section 2 “What you need to know before you take Sunitinib Krka”):

• Heart problems. Tell your doctor if you feel extremely tired, have shortness of breath, or swelling of the feet and ankles. These may be signs of heart problems, including heart failure and heart muscle problems (cardiomyopathy).
• Lung problems or difficulty breathing. Tell your doctor if you develop cough, chest pain, sudden shortness of breath, or coughing up blood. These may be signs 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 the frequency or absence of urination, which may be signs of kidney failure.
• Bleeding. Tell your doctor if you experience any of the following symptoms or severe bleeding during treatment with Sunitinib Krka: stomach (abdominal) pain and swelling; vomiting blood; black, tarry stools; blood in the urine; headache or changes in consciousness; coughing up blood or bloody sputum from the lungs or airways.
• Tumour rupture leading to intestinal perforation. Tell your doctor if you experience severe abdominal pain, fever, nausea, vomiting, blood in the stool, or changes in bowel function.

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

• Decreased number of platelets, red blood cells, and/or white blood cells (e.g. neutrophils)
• Shortness of breath
• High blood pressure
• Extreme tiredness, loss of strength
• Swelling due to fluid accumulation under the skin and around the eyes, deep allergic rash
• Pain and/or irritation in the mouth, painful ulceration and/or inflammation, and/or dry mouth, taste disturbances, stomach disturbances, nausea, vomiting, diarrhoea, constipation, abdominal pain and/or swelling, loss of appetite and/or reduced appetite
• Decreased thyroid activity (hypothyroidism)
• Dizziness
• Headache
• Nosebleeds
• Back pain, joint pain
• Pain in arms and legs
• Yellowing of the skin and/or skin discoloration, excessive skin pigmentation, hair colour changes, rash on palms and soles, rash, dry skin
• Cough
• Fever
• Difficulty sleeping

Common (may affect less than 1 in 10 people)

• Blood clots in blood vessels
• Inadequate blood supply to the heart due to blockage or narrowing of the coronary arteries
• Chest pain
• Reduced amount of blood pumped by the heart
• Fluid retention, including in the lung area
• Infections
• Complication following a severe infection (blood infection), which may lead to tissue damage, organ failure, and death
• Decreased blood sugar level (see section 2, “What you need to know before you take Sunitinib Krka”)
• Loss of protein 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
• Haemorrhoids, anal pain, bleeding gums, difficulty swallowing or loss of swallowing ability
• Burning or painful sensation of the tongue, inflammation of the mucous membrane of the digestive tract, excessive gas in the stomach or intestines
• Weight loss
• Musculoskeletal pain (muscle and bone pain), muscle weakness, muscle fatigue, muscle pain, muscle cramps
• Dryness of the nasal mucous membrane, nasal congestion
• Excessive tearing
• Skin sensation disturbances, itching, skin peeling and inflammation, blisters, acne, nail discoloration, hair loss
• Sensory disturbances in the limbs
• Disorders related to increased or decreased sensitivity, especially to touch
• Heartburn
• Dehydration
• Hot flushes
• Abnormal urine colour
• Depression
• Chills

Uncommon (may affect less than 1 in 100 people)

• Life-threatening infection of soft tissues, including the anorectal area (see section 2, “What you need to know before you take Sunitinib Krka”)
• Stroke
• Heart attack caused by interruption or reduction of blood supply to the heart
• Changes in electrical activity or heart rhythm disorders
• Fluid around the heart (pericardial effusion)
• Liver failure
• Stomach (abdominal) pain due to pancreatitis
• Tumour rupture 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 to the skin
• Mouth pain, tooth and/or jaw pain, swelling or ulceration of the mouth, numbness or heaviness in the jaw, or loose teeth. These may be signs of jaw bone damage (osteonecrosis), see section 2, “What you need to know before you take Sunitinib Krka”
• Excessive production of thyroid hormones leading to increased resting metabolism
• Impaired wound healing after surgical procedures
• Increased activity of a muscle enzyme (creatine phosphokinase) in the blood
• Excessive reaction to allergens, including hay fever, skin rash, itching, hives, swelling of any body part, and breathing difficulties
• Inflammatory condition of the large intestine (colitis, ischaemic colitis)

Rare (may affect less than 1 in 1,000 people)

• Severe reaction affecting the skin and/or mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme)
• Tumour lysis syndrome, a group of metabolic complications that may occur during cancer treatment. These complications are caused by products released from dying tumour cells and may include: nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, and fatigue associated with abnormal laboratory test results (high levels of potassium, uric acid, and phosphorus, and low levels of calcium in the blood), which may lead to kidney changes and acute kidney failure.
• Abnormal muscle breakdown, which may cause kidney disease (rhabdomyolysis)
• Abnormal changes in the brain that may cause a syndrome of symptoms including headache, confusion, seizures, and vision loss (reversible posterior leukoencephalopathy syndrome)
• Painful skin ulceration (pyoderma gangrenosum)
• Hepatitis
• Inflammation of the thyroid gland
• Damage to the smallest blood vessels called thrombotic microangiopathy

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

• Bulging and weakening of a blood vessel wall or rupture of a blood vessel wall (aneurysm and arterial dissection)
• Lack of energy, confusion, drowsiness, loss of consciousness, or coma – these symptoms may indicate toxic effects 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, including any side effects not listed in this leaflet.
You can also report side effects directly via the national reporting system:
Department for Monitoring Adverse Drug Reactions
Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Jerozolimskie Avenue 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the Marketing Authorisation Holder.
Reporting side effects helps provide more information on the safety of the 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 stated on the carton, container, and blister after EXP.
The expiry date refers to the last day of the stated month.
Store in the original packaging to protect from moisture.
No special storage temperature requirements.
Do not use this medicine if you notice the packaging is damaged or shows signs of prior opening.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures 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.
Other ingredients are:

• Capsule contents: 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.
Other ingredients are:

• Capsule contents: 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.
Other ingredients are:

• Capsule contents: 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: hard gelatin capsule with an orange cap and orange body, printed in white ink with “SNB” and “12.5” on the body. The capsule is filled with orange powder. Capsule size: 4 (approximately 14 mm in length).
Sunitinib Krka 25 mg hard capsules
Sunitinib Krka 25 mg: hard gelatin capsule with a caramel (light brown) cap and orange body, printed in white ink with “SNB” and “25” on the body. The capsule is filled with orange powder. Capsule size: 3 (approximately 16 mm in length).
Sunitinib Krka 50 mg hard capsules
Sunitinib Krka 50 mg: hard gelatin capsule with a caramel (light brown) cap and caramel (light brown) body, printed in black ink with “SNB” and “50” on the body. The capsule is filled with orange powder. Capsule size: 1EL (elongated; approximately 20 mm in length).
The medicine is available in HDPE bottles with a PP child-resistant closure, containing a desiccant, with 30 hard capsules in a cardboard box, and in unit-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, The 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 more information about this medicine, contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warsaw
Tel. 22 57 37 500
This medicine is authorised for marketing in the European Economic Area countries under the following names: