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

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 Zentiva is and what it is used for
• 2. Before you take 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 to treat cancer, 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 adults to treat the following types of cancer:

• Gastrointestinal stromal tumour (GIST), a type of cancer of the stomach and intestines, when imatinib is not effective (another anti-cancer medicine) or 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 that arise from cells in the pancreas that produce hormones), which are in an advanced stage and cannot be surgically removed.

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

2. Before you take Sunitinib Zentiva

When not to take Sunitinib Zentiva

• 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 Zentiva, tell your doctor or pharmacist:

• If you have high blood pressure. Sunitinib Zentiva may increase your blood pressure. Your doctor may check your blood pressure during treatment with Sunitinib Zentiva and may prescribe medicines to lower your blood pressure if necessary.
• If you have or have had bleeding or blood disorders. Treatment with Sunitinib Zentiva may increase the risk of bleeding or changes in the number of certain blood cells, which can cause 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 Zentiva.
• If you have heart problems. Sunitinib Zentiva may cause heart problems. Tell your doctor if you experience extreme fatigue, shortness of breath, or swelling of your feet or ankles.
• If you have irregular heart rhythms. Sunitinib Zentiva may cause irregular heart rhythms. During treatment with Sunitinib Zentiva, your doctor may perform an electrocardiogram to assess these irregularities. Tell your doctor if you experience dizziness, fainting, or irregular heartbeat during treatment with Sunitinib Zentiva.
• If you have recently had blood clots in your 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 damage to the small blood vessels (microangiopathic haemolytic anaemia). Tell your doctor if you experience fever, fatigue, weakness, bruising, bleeding, swelling, confusion, loss of vision, or seizures.
• If you have thyroid problems. Sunitinib Zentiva may cause thyroid problems. Tell your doctor if you experience fatigue, feel colder than others, or have a deepened voice during treatment with Sunitinib Zentiva. Your doctor should check your thyroid function before starting treatment with Sunitinib Zentiva 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 pancreatic 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, and pain or discomfort in the right upper abdomen. Your doctor should perform blood tests to check your liver function before starting treatment with Sunitinib Zentiva, 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 Zentiva may affect wound healing. The medicine is usually stopped in patients before surgery. Your doctor will decide when to restart Sunitinib Zentiva.
• A dental examination is recommended before starting treatment with Sunitinib

Sunitinib Zentiva:

• If you experience mouth pain, tooth pain, and/or jaw pain, swelling or ulceration of the mouth, numbness or a feeling of heaviness in the jaw, or tooth mobility, tell your doctor and dentist immediately.
• If you need invasive dental treatment or surgery, tell your dentist that you are taking Sunitinib Zentiva, especially if you are also taking or have taken bisphosphonates intravenously. Bisphosphonates are medicines used to prevent bone problems, which may have been taken for another condition.
• If you have or have had skin and subcutaneous tissue disorders. During treatment with this medicine, you may experience a painful skin rash (pyoderma gangrenosum) or necrotizing fasciitis (a rapidly spreading infection of the skin and/or soft tissues that can be life-threatening). You should contact 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 disorders usually resolve after stopping treatment with Sunitinib Zentiva. During treatment with this medicine, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed, which initially appear as reddened patches similar to targets or circular 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, you should contact 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 the 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 of low blood sugar (fatigue, palpitations, sweating, hunger, and loss of consciousness).

Children and adolescents

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

Sunitinib Zentiva and other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
Some medicines may affect the levels of sunitinib 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,
• products containing St. John's Wort (Hypericum perforatum) - used to treat depression and anxiety disorders.

Taking Sunitinib Zentiva with food and drink

While taking Sunitinib Zentiva, do 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, ask your doctor or pharmacist for advice before taking this medicine.
Women who may become pregnant should use effective contraception during treatment with Sunitinib Zentiva.
Women who are breastfeeding should tell their doctor. You should not breastfeed while taking Sunitinib Zentiva.

Driving and using machines

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

Sunitinib Zentiva contains sodium

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

3. How to take Sunitinib Zentiva

Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
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 once a day for 28 days (4 weeks), followed by a 14-day (2-week) break (without the medicine), in 6-week treatment cycles.
• pNET, the usual dose is 37.5 mg once a day, taken continuously.

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

If you take more Sunitinib Zentiva than you should

If you accidentally take more capsules than you should, tell your doctor immediately, as you may need urgent medical attention.

If you forget to take Sunitinib Zentiva

Do not take a double dose to make up for a forgotten dose.
If you have any further questions on 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.
Tell your doctor immediately if you experience any of the following serious side effects (see also section 2 Before you take Sunitinib Zentiva):
Heart problems. Tell your doctor if you feel extremely tired, have shortness of breath, or swelling of your feet and ankles. These may be symptoms of heart problems, which can include heart failure and heart muscle problems (cardiomyopathy).
Lung problems or breathing difficulties. 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. Tell your doctor if you experience changes in urination or lack of urination, which may be a sign of kidney failure.
Bleeding. Tell your doctor if you experience any of the following symptoms or severe bleeding during treatment with Sunitinib Zentiva: stomach pain and swelling (abdomen), 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.
Tumour breakdown 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 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 fatigue, loss of strength.
• Swelling caused by fluid accumulation under the skin and around the eyes, allergic rash, deep.
• Mouth pain and/or irritation, painful mouth sores and/or inflammation, and/or dry mouth, taste disturbances, stomach upset, nausea, vomiting, diarrhoea, constipation, stomach pain and/or swelling, loss of and/or decreased appetite.
• Decreased thyroid activity (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, rash, dry skin.
• Cough.
• Fever.
• Sleep disturbances.

Common: may affect up to 1 in 10 people

• Blood clots in blood vessels.
• Insufficient blood supply to the heart due to a blockage or narrowing of the coronary arteries.
• Chest pain.
• Decreased amount of blood pumped by the heart.
• Fluid accumulation, including in the lungs.
• Infections.
• A severe infection complication (sepsis) that can cause tissue damage, organ failure, and death.
• Low blood sugar levels (see section 2).
• Protein loss in the 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, anal pain, gum bleeding, difficulty swallowing, or loss of swallowing ability.
• Burning sensation or pain in the mouth, inflammation of the mucous membranes, 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, feeling of nasal congestion.
• Excessive tearing.
• Skin sensitivity disturbances, itching, skin peeling, and/or inflammation, blisters, acne, nail discoloration, hair loss.
• Sensitivity disturbances in the limbs.
• Disturbances related to increased or decreased sensitivity, especially to touch.
• Heartburn.
• Dehydration.
• Hot flashes.
• Abnormal urine colour.
• Depression.
• Chills.

Uncommon: may affect up to 1 in 100 people

• Life-threatening infection of soft tissues, including the perianal area (see section 2).
• Stroke.
• Heart attack caused by interruption or reduction of blood supply to the heart.
• Changes in heart rhythm or electrical activity.
• Fluid accumulation around the heart (pericardial effusion).
• Liver failure.
• Stomach pain (abdomen) caused by pancreatitis.
• Tumour breakdown 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, swelling or ulceration of the mouth, numbness or a feeling of heaviness in the jaw, or tooth mobility. These may be symptoms of jawbone damage (osteonecrosis), see section 2.
• Overproduction of thyroid hormones leading to increased resting metabolism.
• Abnormal wound healing after surgery.
• Increased activity of the muscle enzyme (creatine phosphokinase) in the blood.
• Excessive allergic reaction, including fever, skin rash, itching, hives, swelling of body parts, 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, decreased urine clarity, 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 can lead to kidney changes and acute kidney failure.
• Abnormal muscle breakdown (rhabdomyolysis) that can cause kidney disease.
• Abnormal brain changes that can cause a syndrome of symptoms including headache, disorientation, seizures, and loss of vision (reversible posterior leukoencephalopathy syndrome).
• Painful skin ulcers (pyoderma gangrenosum).
• Liver inflammation.
• Thyroid gland inflammation.
• Damaged small blood vessels (microangiopathic haemolytic anaemia).

Frequency not known (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, disorientation, drowsiness, loss of consciousness/coma - these symptoms may be signs of brain poisoning caused by high levels of ammonia in the blood (hyperammonaemic encephalopathy).

Reporting of side effects

If you experience 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 Department of Drug Safety, 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 or its representative in Poland.
By reporting side effects, you can help 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 which is stated on the carton, bottle, and blister after EXP. The expiry date refers to the last day of that month.
There are no special storage instructions for this medicine.
Do not use this medicine if the packaging is damaged or shows signs of tampering.
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 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 content: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:red iron oxide (E172), titanium dioxide (E171), gelatin.
white printing ink:shellac, titanium dioxide (E171), propylene glycol.
Sunitinib Zentiva, 25 mg, hard capsules
capsule shell:black iron oxide (E172), red iron oxide (E172), yellow iron oxide (E172), titanium dioxide (E171), gelatin.
white printing ink:shellac, titanium dioxide (E171), propylene glycol.
Sunitinib Zentiva, 37.5 mg, hard capsules
capsule shell:yellow iron oxide (E172), titanium dioxide (E171), gelatin.
black printing ink:shellac, black iron oxide (E172), propylene glycol, ammonium hydroxide.
Sunitinib Zentiva, 50 mg, hard capsules
capsule shell:black iron oxide (E172), red iron oxide (E172), yellow iron oxide (E172), titanium dioxide (E171), gelatin.
white printing ink:shellac, titanium dioxide (E171), propylene glycol.

What Sunitinib Zentiva looks like and contents of the pack

Sunitinib Zentiva, 12.5 mg, hard capsules
Orange capsule, size 4 (approximately 14.3 mm in length), with an orange body and orange cap, with white printing "12.5 mg" on the body, containing yellow to orange granules.
Sunitinib Zentiva, 25 mg, hard capsules
Caramel-coloured capsule, size 3 (approximately 15.9 mm in length), with a caramel-coloured cap and orange body, with white printing "25 mg" on the body, containing yellow to orange granules.
Sunitinib Zentiva, 37.5 mg, hard capsules
Yellow capsule, size 2 (approximately 18 mm in length), with a yellow body and yellow cap, with black printing "37.5 mg" on the body, containing yellow to orange granules.
Sunitinib Zentiva, 50 mg, hard capsules
Caramel-coloured capsule, size 1 (approximately 19.4 mm in length), with a caramel-coloured body and caramel-coloured cap, with white printing "50 mg" on the body, containing yellow to orange granules.
Sunitinib Zentiva hard capsules are available in blisters containing 28 hard capsules, single-dose perforated blisters containing 28 x 1 or 30 x 1 hard capsules, or an HDPE bottle 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 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, Netherlands, Lithuania, Latvia, Germany, Czech Republic, Slovakia, Romania, Sweden, Italy, United Kingdom (Northern Ireland):
Sunitinib Zentiva

For further information about this medicine, please contact the Marketing Authorisation Holder in Poland:

Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00
Date of last revision of the leaflet:August 2024