Sunitinib zentiva

Package leaflet: Information for the patient

Sunitinib Zentiva, 12.5 mg, hard capsules
Sunitinib Zentiva, 25 mg, hard capsules
Sunitinib Zentiva, 37.5 mg, hard capsules
Sunitinib Zentiva, 50 mg, hard capsules
Sunitinibum
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 Zentiva is and what it is used for
2. What you need to know before taking Sunitinib Zentiva
3. How to take Sunitinib Zentiva
4. Possible side effects
5. How to store Sunitinib Zentiva
6. Contents of the pack and other information

1. What Sunitinib Zentiva is and what it is used for

Sunitinib Zentiva contains the active substance sunitinib, which is a protein kinase inhibitor.
This medicine is used in the treatment of cancers, as it inhibits the activity of a specific group of proteins
known to be involved in the growth and spread of cancer cells.
Sunitinib Zentiva is used in adult patients for the treatment of the following cancers:

• gastrointestinal stromal tumours (GIST), a type of stomach and intestinal cancer, when imatinib is ineffective (another anticancer medicine) or when the patient cannot take imatinib;
• 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 of the pancreas), which are progressing and cannot be surgically removed.

If you have any questions about how Sunitinib Zentiva works or why your doctor has prescribed it, please consult your doctor.

2. Important information before taking Sunitinib Zentiva

When not to take Sunitinib Zentiva

• if the patient is allergic to sunitinib or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Sunitinib Zentiva, discuss the following with your doctor or pharmacist:

• If the patient has high blood pressure. Sunitinib Zentiva may increase blood pressure. Your doctor may monitor your blood pressure during treatment with Sunitinib Zentiva and, if necessary, may prescribe medicines to lower blood pressure.
• If the patient has or has had blood disorders, bleeding or bruising. Treatment with Sunitinib Zentiva may increase the risk of bleeding or cause changes in the number of certain blood cells, which may lead to anaemia or affect the blood's ability to clot. If the patient is taking warfarin or acenocoumarol, anticoagulant medicines used to prevent blood clots, there may be an increased risk of bleeding. Inform your doctor about any bleeding episodes during treatment with Sunitinib Zentiva.
• If the patient has heart problems. Sunitinib Zentiva may cause heart problems. Inform your doctor if the patient experiences unusual tiredness, shortness of breath, or swelling of the feet or ankles.
• If the patient has heart rhythm disorders. Sunitinib Zentiva may cause heart rhythm disturbances. During treatment with Sunitinib Zentiva, your doctor may perform an electrocardiogram (ECG) to monitor for such disturbances. Inform your doctor if the patient experiences dizziness, fainting, or irregular heartbeat during treatment with Sunitinib Zentiva.
• If the patient has recently had blood clots in veins and/or arteries (types of blood vessels), including stroke, heart attack, pulmonary embolism, or thrombosis. Contact your doctor immediately if, during treatment with Sunitinib Zentiva, the patient experiences 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.
• If the patient has or has had an aneurysm (a bulging and weakening of a blood vessel wall) or a tear in the wall of a blood vessel.
• If the patient has or has had damage to the smallest blood vessels, known as thrombotic microangiopathy. Inform your doctor if the patient develops fever, fatigue, weakness, bruising, bleeding, swelling, confusion, vision loss or seizures.
• If the patient has thyroid problems. Sunitinib Zentiva may cause thyroid problems. Inform your doctor if the patient becomes tired more easily, feels colder than usual, or experiences voice changes during treatment with Sunitinib Zentiva. Your doctor should check thyroid function before starting treatment with Sunitinib Zentiva and regularly during treatment. If the thyroid gland does not produce enough thyroid hormone, the patient may require replacement thyroid hormone therapy.
• If the patient has or has had pancreas or gallbladder problems. Inform your doctor if the patient experiences any of the following symptoms: stomach pain (upper abdomen), nausea, vomiting, or fever. These may be signs of pancreatitis or gallbladder inflammation.
• If the patient has or has had liver problems. Inform your doctor if, during treatment with Sunitinib Zentiva, the patient develops any of the following signs of liver problems: itching, yellowing of the eyes or skin, dark urine, or pain or discomfort in the upper right part of the abdomen. Your doctor should order blood tests to monitor liver function before starting treatment with Sunitinib Zentiva, during treatment, and whenever clinically indicated.
• If the patient has or has had kidney problems. Your doctor will monitor kidney function.
• If the patient is scheduled for surgery or has recently undergone surgery. Sunitinib Zentiva may affect wound healing. The medicine is usually discontinued before surgery. Your doctor will decide when to restart Sunitinib Zentiva.
• The patient is advised to have a dental examination before starting treatment with Sunitinib Zentiva:
• if the patient has or develops mouth pain, tooth or jaw pain, swelling or ulceration of the mouth, numbness or heaviness in the jaw, or loose teeth, inform the oncologist and dentist immediately.
• if the patient requires invasive dental treatment or oral surgery, inform the dentist about taking Sunitinib Zentiva, especially if the patient is currently or has previously received intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone problems, which may have been administered due to another condition.
• If the patient has or has had skin or subcutaneous tissue disorders. During treatment with this medicine, pyoderma gangrenosum (painful skin ulceration) or necrotizing fasciitis (rapidly spreading infection of the skin and/or soft tissues, which may be life-threatening) may occur. Contact your doctor immediately if the patient develops signs of infection around a skin injury, including fever, pain, redness, swelling, or discharge of pus or blood. These conditions usually resolve after stopping treatment with Sunitinib Zentiva. Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed during treatment with this medicine. These initially appear as red, target-like or circular spots, often with centrally located blisters. The rash may progress to extensive blistering or skin peeling and may be life-threatening. If the patient develops a rash or any of the above-mentioned skin symptoms, seek medical attention immediately.
• If the patient has or has had seizures. Inform your doctor as soon as possible if the patient develops high blood pressure, headache, or vision loss.
• If the patient has diabetes. Blood glucose levels should be monitored regularly in diabetic patients to assess whether adjustment of antidiabetic medication is needed to minimize the risk of hypoglycaemia. Inform your doctor immediately if the patient experiences symptoms of low blood sugar (tiredness, palpitations, excessive sweating, hunger, or loss of consciousness).

Children and adolescents
Sunitinib Zentiva should not be used in children and adolescents under 18 years of age.

Sunitinib Zentiva with other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.
Some medicines may affect the concentration of sunitinib in the body. Inform your doctor if the patient is 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 conditions),
• phenytoin, carbamazepine, phenobarbital – used to treat epilepsy and other neurological conditions,
• products containing St John’s wort (Hypericum perforatum) – used to treat depression and anxiety.

Taking Sunitinib Zentiva with food and drink
Do not drink grapefruit juice during treatment with Sunitinib Zentiva.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor or pharmacist before using this medicine.
Women of childbearing potential should use an effective method of contraception during treatment with Sunitinib Zentiva.
Breastfeeding women should inform their doctor. Breastfeeding is not recommended during treatment with Sunitinib Zentiva.

Driving and operating machinery
If dizziness or significant fatigue occurs, exercise particular caution when driving or operating machinery.

Sunitinib Zentiva contains sodium.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is considered "sodium-free".

3. How to take Sunitinib Zentiva

This medicine should always be taken as prescribed by the doctor. In case of doubts, consult the
doctor or pharmacist.
The doctor will prescribe the appropriate dose for the individual patient, depending on the type of tumour.
For patients being treated for:

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

The doctor will determine the appropriate dose for the individual patient and the time when treatment with
Sunitinib Zentiva should end.
Sunitinib Zentiva may be taken with or without food.
Taking more Sunitinib Zentiva than prescribed
If the patient accidentally takes more capsules than recommended, contact the doctor immediately,
as the patient may require urgent medical attention.
Missing a dose of Sunitinib Zentiva
Do not take a double dose to make up for a missed dose.
If there are any further doubts regarding the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Contact a doctor immediately if the patient experiences any of the following serious adverse reactions (see also Important information before taking Sunitinib Zentiva):
Heart problems. Tell the doctor if the patient feels very tired, has shortness of breath, or swelling of the feet and ankles. These may be symptoms of heart problems, which may include heart failure and diseases affecting the heart muscle (cardiomyopathy).
Lung diseases or breathing difficulties. Tell the doctor if the patient develops cough, chest pain, sudden onset of 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 function disorders. Tell the doctor if the patient experiences changes in frequency or absence of urination, which may be symptoms of kidney failure.
Bleeding. Tell the doctor if the patient experiences any of the following symptoms or severe bleeding during treatment with Sunitinib Zentiva: stomach (abdominal) pain and swelling, vomiting blood, black and sticky stools, blood in the urine, headache or changes in consciousness, coughing up blood or bloody sputum from the lungs or airways.
Tumour lysis leading to intestinal perforation. Tell the doctor if the patient experiences severe abdominal pain, fever, nausea, vomiting, blood in the stool, or changes in bowel habits.

Other adverse reactions associated with sunitinib 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.
• Hypertension.
• Extreme fatigue, 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 dryness of the mouth, taste disturbances, gastric 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 color changes, hand-foot skin reaction, rash, dry skin.
• Cough.
• Fever.
• Difficulty falling asleep.

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 lung area.
• Infections.
• Severe infection complication (blood infection), which may lead to tissue damage, organ failure, and death.
• Low blood sugar levels (see section 2).
• Protein loss in urine, sometimes causing swelling.
• Flu-like symptoms.
• Abnormal blood test results, including pancreatic and liver enzymes.
• High levels of uric acid in the blood.
• Haemorrhoids, rectal pain, bleeding gums, difficulty swallowing or loss of swallowing ability.
• Burning or painful sensation of the tongue, inflammation of the mucous membranes of the gastrointestinal 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 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 color.
• Depression.
• Chills.

Uncommon: may affect up to 1 in 100 people

• Life-threatening soft tissue infections, including in the anogenital area (see section 2).
• Stroke.
• Myocardial infarction 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.
• Abdominal pain caused by inflammation of the pancreas (pancreatitis).
• Tumour lysis 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 of the jaw, or loose teeth. These may be symptoms of jaw bone damage (osteonecrosis), see section 2.
• Excessive production of thyroid hormones leading to increased resting metabolism.
• Impaired healing of surgical wounds.
• Increased activity of muscle enzyme (creatine phosphokinase) in blood.
• Excessive reaction to allergens, including hay fever, skin rash, itching, urticaria, swelling of body parts, and breathing difficulties.
• Inflammatory condition of the large intestine (colitis, ischemic colitis).

Rare: may affect up to 1 in 1000 people

• Severe skin and/or mucosal reaction (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 phosphate, and low calcium levels in blood), which may lead to kidney changes and acute kidney failure.
• Abnormal muscle breakdown that 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 known as thrombotic microangiopathy.

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

• Enlargement and weakening of the blood vessel wall or rupture of the blood vessel wall (aneurysm and arterial dissection).
• Lack of energy, disorientation, drowsiness, loss of consciousness/coma – these symptoms may indicate brain toxicity caused by high levels of ammonia in the blood (hyperammonaemic encephalopathy).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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.
Adverse reactions can also be reported to the marketing authorisation holder or its representative in Poland.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Sunitinib Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, bottle and blister
after: EXP. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Do not use this medicine if the packaging is damaged or shows signs of prior opening.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Sunitinib Zentiva contains

• The active substance is sunitinib.

Sunitinib Zentiva 12.5 mg, hard capsules:
each capsule contains 12.5 mg of sunitinib.
Sunitinib Zentiva 25 mg, hard capsules:
each capsule contains 25 mg of sunitinib.
Sunitinib Zentiva 37.5 mg, hard capsules:
each capsule contains 37.5 mg of sunitinib.
Sunitinib Zentiva 50 mg, hard capsules:
each capsule contains 50 mg of sunitinib.

• Other ingredients are:
  Capsule contents: microcrystalline cellulose, mannitol, sodium croscarmellose (see section 2 "Sunitinib Zentiva contains sodium"), povidone K30, magnesium stearate.

Sunitinib Zentiva 12.5 mg, hard capsules
Capsule shell: iron oxide red (E172), titanium dioxide (E171), gelatin.
Printing ink, white: shellac, titanium dioxide (E171), propylene glycol.

Sunitinib Zentiva 25 mg, hard capsules
Capsule shell: iron oxide black (E172), iron oxide red (E172), iron oxide yellow (E172), titanium dioxide (E171), gelatin.
Printing ink, white: shellac, titanium dioxide (E171), propylene glycol.

Sunitinib Zentiva 37.5 mg, hard capsules
Capsule shell: iron oxide yellow (E172), titanium dioxide (E171), gelatin.
Printing ink, black: shellac, iron oxide black (E172), propylene glycol, ammonium hydroxide.

Sunitinib Zentiva 50 mg, hard capsules
Capsule shell: iron oxide black (E172), iron oxide red (E172), iron oxide yellow (E172), titanium dioxide (E171), gelatin.
Printing ink, white: shellac, titanium dioxide (E171), propylene glycol.

What Sunitinib Zentiva looks like and contents of the pack
Sunitinib Zentiva 12.5 mg, hard capsules
Orange-bodied and orange-capped size 4 gelatin capsule (approximately 14.3 mm in length), with white printing "12.5 mg" on the body, containing yellow to orange granules.

Sunitinib Zentiva 25 mg, hard capsules
Orange-bodied and caramel-capped size 3 gelatin capsule (approximately 15.9 mm in length), with white printing "25 mg" on the body, containing yellow to orange granules.

Sunitinib Zentiva 37.5 mg, hard capsules
Yellow-bodied and yellow-capped size 2 gelatin capsule (approximately 18 mm in length), with black printing "37.5 mg" on the body, containing yellow to orange granules.

Sunitinib Zentiva 50 mg, hard capsules
Caramel-bodied and caramel-capped size 1 gelatin capsule (approximately 19.4 mm in length), with white printing "50 mg" on the body, containing yellow to orange granules.

Sunitinib Zentiva, hard capsules, is available in blisters containing 28 hard capsules, single-dose perforated blister packs containing 28 x 1 or 30 x 1 hard capsules, or in HDPE bottles containing 30 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva k.s.
U kabelovny 130, Dolni Mĕcholupy
102 37 Prague 10, Czech Republic

Manufacturer
Remedica Ltd.
Aharnon Street, Limassol Industrial Estate
3056 Limassol
Cyprus

Pharmacare Premium Ltd.
HHF003 Hal Far Industrial Estate
Birzebbugia, BBG3000
Malta

This medicinal product is authorised for marketing in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Bulgaria:
Сунитиниб Зентива / Sunitinib Zentiva

Denmark, Estonia, France, Germany, the Netherlands, Lithuania, Latvia, the Czech Republic, the Slovak Republic, Romania, Sweden, Italy, United Kingdom (Northern Ireland):
Sunitinib Zentiva

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
Tel: +48 22 375 92 00