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 experience any side effects, including any not listed in this leaflet, tell your doctor. See section 4.

Contents of the leaflet

1. What Sunitinib Krka is and what it is used for
2. What you need to know 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 Sunitinib Krka is and what it is used for
Sunitinib Krka contains sunitinib as the active substance, which is a protein kinase inhibitor.
Sunitinib Krka is used to treat certain types of cancer. It inhibits 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 it has been prescribed, ask your doctor.

2. What you need to know before taking 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 cause changes in certain blood cell counts, which may lead to 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 that occurs while taking 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 or have had heart rhythm disorders. Sunitinib Krka may cause irregular heart rhythm. Your doctor may perform an electrocardiogram (ECG) during treatment with Sunitinib Krka to monitor for such disorders. Tell your doctor if you experience dizziness, fainting, or irregular heartbeat while taking Sunitinib Krka.
• If you have recently had blood clots in your veins and/or arteries, including stroke, heart attack, embolism, or thrombosis. Contact your doctor immediately if you experience symptoms such as chest pain or tightness, pain in 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 weakened and bulging blood vessel wall) or arterial dissection (a tear in the blood vessel wall).
• If you have or have had damage to the smallest blood vessels known as thrombotic microangiopathy. Tell your doctor if you develop fever, fatigue, weakness, bruising, bleeding, swelling, confusion, vision loss, or seizures.
• If you have or have had thyroid gland 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 and regularly during treatment with Sunitinib Krka. If your thyroid does not produce enough 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, or fever. These may be symptoms of pancreatitis or gallbladder inflammation.
• If you have or have had liver disease. 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 urine, or pain or discomfort in the upper right abdomen. Your doctor should perform blood tests to check liver function before starting and during treatment with Sunitinib Krka, and if clinically indicated.
• If you have or have had kidney disease. Your doctor will monitor kidney function.
• If you are scheduled for 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.
• It is recommended that you have a dental examination before starting treatment with Sunitinib Krka:
• If you have or develop mouth pain, tooth or jaw pain, swelling or ulceration in 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, which may be life-threatening) may occur. Contact your doctor immediately if you develop signs of infection around a skin wound, 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-like or circular skin spots, often with centrally located blisters. The rash may progress to extensive blistering or skin peeling and may be life-threatening. If you develop a rash or the above skin symptoms, seek medical advice immediately.
• If you have or have had seizures. Inform your doctor as soon as possible if you develop high blood pressure, headache, or vision loss.
• If you have diabetes. Blood glucose levels should be monitored regularly in diabetic patients to assess whether adjustment of antidiabetic medication is needed to minimise the risk of low blood sugar. Inform your doctor immediately 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.
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 in various diseases (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, talk to your doctor or pharmacist before taking this medicine.
Women who could become pregnant should use an effective method of contraception during treatment with Sunitinib Krka.
Breastfeeding women should inform their doctor. Breastfeeding must not be undertaken while taking Sunitinib Krka.

Driving and using machines
Exercise caution when driving or operating machinery if you experience dizziness or extreme tiredness.

Sunitinib Krka contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially “sodium-free”.

3. How to take Sunitinib Krka
Always take this medicine exactly as your doctor has told you. Ask your doctor or pharmacist 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 may be taken with or without food.

How to take this medicine
Do not press the capsules out of the foil blister, as this may damage them. Capsules should be removed by peeling off 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 off.
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 forgotten 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 taking Sunitinib Krka”):

• Heart problems. Tell your doctor if you feel very tired, have shortness of breath, or swelling of the feet and ankles. These may be symptoms of heart problems, including heart failure or heart muscle problems (cardiomyopathy).
• Lung disease or breathing difficulties. Tell your doctor if you develop cough, chest pain, sudden shortness of breath, or coughing up blood. These may be symptoms of pulmonary embolism, a condition that occurs when blood clots travel to the lungs.
• Kidney problems. Tell your doctor if you experience changes in urine frequency or absence of urination, which may be symptoms of kidney failure.
• Bleeding. Tell your doctor if you experience any of the following symptoms or severe bleeding while taking 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 platelet, red blood cell, and/or white blood cell (e.g. neutrophil) counts
• 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
• Mouth pain and/or irritation, painful ulceration and/or inflammation, and/or dry mouth, taste disturbances, stomach disturbances, nausea, vomiting, diarrhoea, constipation, abdominal pain and/or swelling, loss of 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 up to 1 in 10 people)

• Blood clots in blood vessels
• Inadequate blood supply to the heart due to embolism or narrowing of the coronary arteries
• Chest pain
• Reduced amount of blood pumped by the heart
• Fluid retention, including in the lungs
• Infections
• Complication following severe infection (sepsis), which may lead to tissue damage, organ failure, and death
• Low blood sugar levels (see section 2, “What you need to know 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
• Haemorrhoids, anal pain, bleeding gums, difficulty or inability to swallow
• Burning or painful sensation in the tongue, inflammation of the gastrointestinal mucosa, 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 mucosa, sensation of nasal congestion
• Excessive tearing
• Skin sensation disturbances, itching, skin peeling and inflammation, blisters, acne, nail discoloration, hair loss
• Sensory disturbances in limbs
• Disorders related to increased or decreased sensitivity, especially to touch
• Heartburn
• Dehydration
• Hot flushes
• Abnormal urine colour
• Depression
• Chills

Uncommon (may affect up to 1 in 100 people)

• Life-threatening soft tissue infections, including in the anogenital area (see section 2, “What you need to know before taking Sunitinib Krka”)
• Stroke
• Heart attack caused by interruption or reduction of blood supply to the heart
• Changes in electrical function or rhythm disturbances of the heart
• 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 or jaw pain, swelling or ulceration in the mouth, numbness or heaviness in the jaw, or loose teeth. These may be symptoms of jaw bone damage (osteonecrosis), see section 2, “What you need to know before taking 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
• Inflammation of the large intestine (colitis, ischemic colitis)

Rare (may affect up to 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 the breakdown products of 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 phosphate, 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
• Thyroid gland inflammation
• Damage to the smallest blood vessels known as thrombotic microangiopathy

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

• Enlargement and weakening of the blood vessel wall or rupture of the 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 experience any side effects, including any not listed in this leaflet, tell your doctor. Side effects can also be reported directly to the Department for Monitoring Adverse Drug Reactions of the 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
Side effects can also be reported to the Marketing Authorisation Holder.
Reporting side effects helps 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 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 temperature storage conditions are required.
Do not use this medicine if 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 contains 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 contains 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 contains orange powder. Capsule size: 1EL (elongated; approximately 20 mm in length).
The medicine is available in HDPE bottles with PP child-resistant closure and desiccant, containing 30 hard capsules in a cardboard box, and in single-dose blisters with 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
Manufacturers:
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 further 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 sale in the European Economic Area countries under the following names: