Sunitinib Zentiva

Leaflet attached to the packaging: patient information

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

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor. See section 4.

Table of contents of the leaflet

• 1. What is Sunitinib Zentiva and what is it used for
• 2. Important information 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 is Sunitinib Zentiva and what is it 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 special group of proteins,
known to participate in the growth and spread of cancer cells.
Sunitinib Zentiva is used in adult patients to treat the following cancers:

• gastrointestinal stromal tumors (GIST), a type of stomach and intestinal cancer, when imatinib is ineffective (another anticancer drug) 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 tumors (pNET) (tumors that arise from pancreatic hormone-producing cells), 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 for you,
you should consult your doctor.

2. Important information before taking Sunitinib Zentiva

When not to take Sunitinib Zentiva

Warnings and precautions

Before starting treatment with Sunitinib Zentiva, you should discuss it with your doctor or pharmacist:

• If you have high blood pressure. Sunitinib Zentiva may increase blood pressure. Your doctor may monitor your blood pressure during treatment with Sunitinib Zentiva and may prescribe blood pressure-lowering medications if necessary.
• If you have or have had blood disorders, bleeding, or bruising. Treatment with Sunitinib Zentiva may increase the risk of bleeding or change the number of certain blood cells, which can cause anemia or affect the blood's ability to clot. If you are taking warfarin or acenocoumarol, blood-thinning medications used to prevent blood clots, there may be a higher risk of bleeding. You should tell your doctor about all bleeding episodes while taking Sunitinib Zentiva.
• If you have heart problems. Sunitinib Zentiva may cause heart problems. You should tell your doctor if you experience fatigue, shortness of breath, or swelling of the feet or ankles.
• If you have heart rhythm disorders. Sunitinib Zentiva may cause heart rhythm disorders. During treatment with Sunitinib Zentiva, your doctor may perform an electrocardiogram to assess these disorders. You should tell your doctor if you experience dizziness, fainting, or irregular heartbeat while taking Sunitinib Zentiva.
• If you have recently had blood clots in the 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 smallest blood vessels (microangiopathic thrombocytopenia). You should 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. You should tell your doctor if you experience fatigue, feel colder than others, or have a deepened voice while taking 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 disorders or problems with the gallbladder. You should 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 or have had liver disease. You should inform your doctor if you experience any of the following symptoms of liver disorders while taking Sunitinib Zentiva: 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 liver function before starting treatment with Sunitinib Zentiva, during treatment, and if there are clinical signs.
• If you have or have had kidney disease. 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 discontinued in patients before surgery. Your doctor will decide when to restart Sunitinib Zentiva.
• A dental examination is recommended before starting treatment with Sunitinib

Zentiva:

• If you have or have had skin and subcutaneous tissue disorders. While taking this medicine, you may experience pyoderma gangrenosum (painful skin ulcers) or necrotizing fasciitis (a rapidly spreading infection of the skin and/or soft tissues that can be life-threatening). You should immediately contact your doctor if you experience symptoms of infection around a skin lesion, including fever, pain, redness, swelling, or discharge of pus or blood. These disorders usually resolve after discontinuation of Sunitinib Zentiva. While taking this medicine, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed, which initially appear as reddened patches with a target-like shape or round patches, often with centrally located blisters. The rash can transform into widespread blisters or skin peeling and can be life-threatening. If you experience a rash or the above-mentioned skin symptoms, you should immediately consult your doctor.
• If you have or have had seizures. You should inform 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 it is necessary to adjust the dose of the anti-diabetic medication to minimize the risk of hypoglycemia. You should inform 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 Zentiva should not be used in children and adolescents under 18 years of age.

Sunitinib Zentiva and other medicines

You should 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 level of sunitinib in your body. You should inform 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, you should not drink grapefruit juice.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor or pharmacist before taking this medicine.
Women who may become pregnant should use effective contraception during treatment with Sunitinib Zentiva.
Women who are breastfeeding should inform their doctor. You should not breastfeed while taking Sunitinib Zentiva.

Driving and using machines

If you experience dizziness or significant fatigue, you should be careful while driving or operating machinery.

Sunitinib Zentiva contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per dose, which means the medicine is considered "sodium-free".

3. How to take Sunitinib Zentiva

You should always take this medicine exactly as your doctor has told you. If you are not sure, you should ask your doctor or pharmacist.
Your doctor will prescribe a dose suitable for you, depending on the type of cancer.
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 appropriate dose for you and when to stop taking Sunitinib Zentiva.
Sunitinib Zentiva can be taken with or without food.

Taking more than the recommended dose of Sunitinib Zentiva

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

Missing a dose of Sunitinib Zentiva

You should not take a double dose to make up for a missed dose.
If you have any further questions about taking this medicine, you should ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You should contact your doctor immediately if you experience any of the following serious side effects (see also Important information before taking Sunitinib Zentiva):
Heart problems. You should 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, which can include heart failure and heart muscle disorders (cardiomyopathy).
Lung problems or breathing difficulties. You should 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. You should tell your doctor if you experience disturbed or absent urination, which may be a sign of kidney failure.
Bleeding. You should tell your doctor if you experience any of the following symptoms or severe bleeding while taking Sunitinib Zentiva: stomach pain and swelling, vomiting blood, black and tarry stools, blood in the urine, headache, or changes in consciousness, coughing up blood or bloody sputum from the lungs or airways.
Tumor breakdown leading to bowel perforation. You should tell your doctor if you experience severe abdominal pain, fever, nausea, vomiting, blood in the stool, or changes in bowel function.
Other side effects of sunitinib may include:
Very common: may affect more than 1 in 10 people

• Decreased 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 rash.
• Pain and/or irritation in the mouth, painful ulcers, and/or inflammation, and/or dryness of the mouth, taste disorders, stomach disorders, nausea, vomiting, diarrhea, constipation, abdominal 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 color changes, rash on the palms and soles, rash, dry skin.
• Cough.
• Fever.
• Sleep disorders .

Common: may affect up to 1 in 10 people

• Blood clots in blood vessels.
• Inadequate 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 complication of severe infection (blood infection), which can lead to tissue damage, organ failure, and death.
• Decreased 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.
• Hemorrhoids, anal pain, gum bleeding, difficulty swallowing, or loss of swallowing ability.
• Burning or pain in the mouth, inflammation of the mucous membrane of the digestive system, 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 disorders, itching, skin peeling, and/or inflammation, blisters, acne, nail discoloration, hair loss.
• Skin sensation disorders.
• Sensitivity disorders related to increased or decreased sensitivity, especially to touch.
• Heartburn.
• Dehydration.
• Hot flashes.
• Abnormal urine color.
• 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 (abdominal pain) caused by pancreatitis.
• Tumor breakdown leading to bowel perforation.
• Inflammation (swelling or redness) 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 mouth ulcers, numbness, or a feeling of heaviness in the jaw, or tooth mobility. These may be symptoms of jawbone damage (osteonecrosis), see section 2.
• Excessive production 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 hay fever, skin rash, itching, hives, swelling of body parts, and breathing difficulties.
• Inflammation of the large intestine (colitis, ischemic colitis).

Rare: may affect up to 1 in 1000 people

• Severe skin and/or mucous membrane reaction (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).
• Tumor lysis syndrome, which is 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, lack of 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, which can cause kidney disease (rhabdomyolysis).
• Abnormal brain changes, which can cause a syndrome of symptoms including headache, disorientation, seizures, and loss of vision (reversible posterior leukoencephalopathy syndrome).
• Painful skin ulcers (pyoderma gangrenosum).
• Hepatitis.
• Thyroid inflammation.
• Damaged smallest blood vessels (microangiopathic thrombocytopenia).

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 (hyperammonemic encephalopathy).

Reporting side effects

If you experience any side effects, including any side effects not listed in the leaflet, you should tell your doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products 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 authorization 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

The medicine should be stored out of 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 month stated.
There are no special storage instructions for this medicine.
Do not use this medicine if 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. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Sunitinib Zentiva contains

• The active substance of the medicine 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 carmellose (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 shellyellow 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 (E 171), 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
The capsule is a size 4 (approximately 14.3 mm long) gelatin capsule 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
The capsule is a size 3 (approximately 15.9 mm long) gelatin capsule with a caramel cap and orange body, with white printing "25 mg" on the body, containing yellow to orange granules.
Sunitinib Zentiva, 37.5 mg, hard capsules
The capsule is a size 2 (approximately 18 mm long) gelatin capsule 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
The capsule is a size 1 (approximately 19.4 mm long) gelatin capsule with a caramel body and caramel 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 blisters perforated 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 authorization 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 authorized 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, you should contact the representative of the marketing authorization holder in Poland:

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