Sunitinib Sinthon

Leaflet accompanying the packaging: information for the user

Sunitinib Synthon, 12.5 mg, hard capsules

Sunitinib Synthon, 25 mg, hard capsules

Sunitinib Synthon, 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.
• In case of any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed to you specifically. 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 Synthon and what is it used for
• 2. Important information before taking Sunitinib Synthon
• 3. How to take Sunitinib Synthon
• 4. Possible side effects
• 5. How to store Sunitinib Synthon
• 6. Contents of the packaging and other information

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

Sunitinib Synthon contains the active substance sunitinib, which is a protein kinase inhibitor. Sunitinib Synthon is used to treat cancer. It inhibits the activity of a special group of proteins known to be involved in the growth and spread of cancer cells.
Sunitinib Synthon is used to treat the following types of cancer in adults:

• gastrointestinal stromal tumors (GIST), a type of stomach and intestine cancer, when imatinib (another anticancer drug) has stopped working or the patient cannot take it;
• 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 hormone-producing cells in the pancreas) that are progressing or cannot be surgically removed.

If you have any questions about how Sunitinib Synthon works or why it has been prescribed, you should consult your doctor.

2. Important information before taking Sunitinib Synthon

When not to take Sunitinib Synthon

• 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 to take Sunitinib Synthon, you should discuss it with your doctor:

• If you have high blood pressure. Sunitinib Synthon may increase blood pressure. Your doctor may check your blood pressure during treatment with Sunitinib Synthon, and you may need to be treated with blood pressure-lowering medicines.
• If you have or have had blood disorders, bleeding, or bruising. Treatment with Sunitinib Synthon 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 medicines used to prevent blood clots, you may be at increased risk of bleeding. You should tell your doctor about any bleeding during treatment with Sunitinib Synthon.
• If you have heart problems. Sunitinib Synthon may cause heart problems. You should tell your doctor if you experience fatigue, shortness of breath, or swelling of your feet or ankles.
• If you have heart rhythm disorders. Sunitinib Synthon may cause abnormal heart rhythms. During treatment with Sunitinib Synthon, your doctor may perform an electrocardiogram to assess these disorders. You should tell your doctor if you experience dizziness, fainting, or abnormal heart rhythms while taking Sunitinib Synthon.
• If you have recently had problems with 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, or 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 called thrombotic microangiopathy. 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 Synthon may cause thyroid problems. You should tell your doctor if you easily get tired, feel colder than other people, or experience a deepened voice while taking Sunitinib Synthon. Your doctor should check your thyroid function before starting Sunitinib Synthon and regularly during treatment. If your thyroid does not produce enough thyroid hormone, you may need to be treated with replacement thyroid hormone.
• If you have or have had problems with your pancreas or 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 problems. You should inform your doctor if you experience any of the following symptoms of liver disorders while taking Sunitinib Synthon: itching, yellowing of the eyes or skin, dark urine, or pain or discomfort in the right upper abdomen. Your doctor should perform blood tests to check liver function before starting Sunitinib Synthon, during treatment, and if there are clinical signs.

and

• If you have or have had kidney problems. Your doctor will monitor your kidney function.
• If you are going to have surgery or have recently had surgery. Sunitinib Synthon may affect wound healing. Sunitinib Synthon is usually discontinued in patients before surgery. Your doctor will decide when to restart Sunitinib Synthon.
• You are advised to have a dental check-up before starting treatment with Sunitinib Synthon:
• if you experience or have experienced mouth pain, toothache, and/or jaw pain, swelling, or mouth ulceration, numbness, or a feeling of heaviness in the jaw, or tooth mobility, you should immediately inform your oncologist and dentist.
• if you need invasive dental treatment or oral surgery, you should inform your dentist that you are taking Sunitinib Synthon, 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, you may experience pyoderma gangrenosum (painful skin ulceration) 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 injury, including fever, pain, redness, swelling, or discharge of pus or blood. These disorders usually resolve after discontinuation of sunitinib. While taking sunitinib, 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 peeling of the skin and can 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. 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 medicine to minimize the risk of low blood sugar. 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 Synthon is not recommended for patients under 18 years of age.

Sunitinib Synthon and other medicines

You should tell your doctor or pharmacist about all medicines you are taking or have recently taken, including those obtained without a prescription, and about medicines you plan to take.
Some medicines may affect the levels of Sunitinib Synthon 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,
• herbal products containing St. John's Wort (Hypericum perforatum) - used to treat depression and anxiety disorders.

Taking Sunitinib Synthon with food and drink

While taking Sunitinib Synthon, 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 Synthon.
Women who are breastfeeding should inform their doctor. You should not breastfeed while taking Sunitinib Synthon.

Driving and using machines

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

Sunitinib Synthon contains sodium

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

3. How to take Sunitinib Synthon

This medicine should always be taken exactly as your doctor has told you. If you are not sure, you should ask your doctor.
Your doctor will prescribe the dose that is right for you, depending on the type of cancer. For patients being treated for:

• GIST or MRCC: the usual dose is 50 mg taken 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 taken once a day continuously.

Your doctor will determine the correct dose for you and when to stop taking Sunitinib Synthon.
Sunitinib Synthon can be taken with or without food.
To open the blisters, you should tear off a single dose from the blister using the perforation line. Then, peel off the foil from the blister and remove the capsule. You should not push the capsule through the foil, as this may damage the capsule.

Taking a higher dose of Sunitinib Synthon than recommended

If you have taken too many capsules, you should contact your doctor immediately.
Medical intervention may be necessary.

Missing a dose of Sunitinib Synthon

You should not take a double dose to make up for a missed dose.

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 side effects (see also section 2, "Important information before taking Sunitinib Synthon"):

• heart problems. You should tell your doctor if you feel very 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 problems with the heart muscle (cardiomyopathy).
• lung or breathing problems. 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 during treatment with Sunitinib Synthon: 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.
• tumor lysis syndrome leading to intestinal perforation. You should tell your doctor if you experience severe abdominal pain, fever, nausea, vomiting, blood in stool, or changes in bowel movements.

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

• decrease in the 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 rash
• mouth pain, toothache, and/or jaw pain, mouth ulceration, painful swelling, and/or inflammation, and/or dryness of the mouth, taste disturbances, stomach upset, nausea, vomiting, diarrhea, constipation, abdominal pain and/or swelling
• decrease in thyroid activity (hypothyroidism)
• dizziness
• headache
• nosebleeds
• back pain, joint pain
• arm and leg pain
• yellowing of the skin and/or discoloration, excessive pigmentation of the skin, hair color 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
• decrease in the amount of blood pumped by the heart
• fluid accumulation, including in the lungs
• infections
• complication after a severe infection (sepsis), which can cause tissue damage, organ failure, and death
• decrease in blood sugar levels (see section 2, "Important information before taking Sunitinib Synthon").
• 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
• hemorrhoids, anal pain, gum bleeding, difficulty swallowing, or loss of swallowing ability
• tongue pain, mouth ulcers, inflammation of the mucous membranes, and/or dryness of the mouth, gastrointestinal disturbances, nausea, vomiting, diarrhea, constipation
• 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 sensation disturbances, itching, peeling, and/or inflammation of the skin, blisters, acne, nail discoloration, hair loss
• skin sensation disturbances in the limbs
• disturbances 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, "Important information before taking Sunitinib Synthon").
• stroke
• heart attack caused by interruption or reduction of blood supply to the heart
• changes in the electrical or rhythm activity of the heart.
• fluid accumulation around the heart (pericardial effusion)
• liver failure
• stomach pain (abdomen) caused by pancreatitis
• tumor lysis syndrome leading to intestinal perforation (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, toothache, and/or jaw pain, mouth ulceration, numbness, or a feeling of heaviness in the jaw, or tooth mobility. These may be symptoms of jawbone damage (osteonecrosis), see section 2, "Important information before taking Sunitinib Synthon".
• excessive production of thyroid hormones leading to increased resting metabolism
• impaired wound healing after surgical procedures
• increased activity of the muscle enzyme (creatine phosphokinase) in the blood.
• excessive allergic reaction, including fever, skin rash, itching, hives, swelling of any part of the body, and breathing difficulties
• inflammation of the large intestine (colitis, ischemic colitis)

Rare(may affect up to 1 in 1,000 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 ulceration (pyoderma gangrenosum)
• hepatitis
• thyroiditis
• damage to the smallest blood vessels called thrombotic microangiopathy

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

• enlargement and weakening of the wall of a blood vessel or rupture of the wall of a blood vessel (aneurysm and arterial dissection)

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +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.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sunitinib Synthon

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, container, and blister after: EXP. The expiry date refers to the last day of the month stated.
Store in the original packaging to protect from moisture.
This medicine does not require any special storage conditions.
Do not use this medicine if you notice that 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 packaging and other information

What Sunitinib Synthon contains

[Sunitinib Synthon, 12.5 mg, hard capsules]
The active substance of Sunitinib Synthon is sunitinib. Each hard capsule contains sunitinib malate equivalent to 12.5 mg of sunitinib.
Other ingredients are:

• Capsule content:povidone, microcrystalline cellulose, sodium croscarmellose (see section 2, "Sunitinib Synthon contains sodium"), magnesium stearate;
• Capsule shell:gelatin, titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172).
• Printing ink:shellac, titanium dioxide (E171), propylene glycol.

[Sunitinib Synthon, 25 mg, hard capsules]
The active substance of Sunitinib Synthon is sunitinib. Each hard capsule contains sunitinib malate equivalent to 25 mg of sunitinib.
Other ingredients are:

• Capsule content:povidone, microcrystalline cellulose, sodium croscarmellose (see section 2, "Sunitinib Synthon contains sodium"), magnesium stearate;
• Capsule shell:gelatin, titanium dioxide (E171), iron oxide red (E172).
• Printing ink:shellac, titanium dioxide (E171), propylene glycol.

[Sunitinib Synthon, 50 mg, hard capsules]
The active substance of Sunitinib Synthon is sunitinib. Each hard capsule contains sunitinib malate equivalent to 50 mg of sunitinib.
Other ingredients are:

• Capsule content:povidone, microcrystalline cellulose, sodium croscarmellose (see section 2, "Sunitinib Synthon contains sodium"), magnesium stearate;
• Capsule shell:gelatin, titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172), iron oxide black (E172).
• Printing ink:shellac, iron oxide black (E172), propylene glycol.

What Sunitinib Synthon looks like and contents of the pack

[Sunitinib Synthon, 12.5 mg, hard capsules]
Sunitinib Synthon 12.5 mg: orange hard capsule (capsule) with a white imprint: "SNB" and "12.5" on the body.
The capsule is filled with an orange powder. Capsule size: 4 (length approximately 14 mm).
[Sunitinib Synthon, 25 mg, hard capsules]
Sunitinib Synthon 25 mg: hard capsule (capsule) with a caramel (light brown) cap and an orange body, with a white imprint: "SNB" and "25" on the body. The capsule is filled with an orange powder. Capsule size: 3 (length approximately 16 mm).
[Sunitinib Synthon, 50 mg, hard capsules]
Sunitinib Synthon 50 mg: hard capsule (capsule) with a caramel cap and a caramel (light brown) body, with a black imprint: "SNB" and "50" on the body. The capsule is filled with an orange powder. Capsule size: 1EL (elongated; length approximately 20 mm).
The medicine is available in HDPE plastic containers with a PP child-resistant closure containing 30 capsules, in a cardboard box or in peel-off blisters with a desiccant containing 28 or 30 capsules, in a cardboard box or in single-dose blisters containing 28 x 1 or 30 x 1 capsules in a cardboard box.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:
Synthon B.V., Microweg 22, 6545 CM Nijmegen, Netherlands
Manufacturer:
Synthon Hispania S.L., Calle De Castello 1, Poligono Las Salinas, 08830 Sant Boi de Llobregat,
Spain
To obtain more detailed information on the names of medicinal products in other European Economic Area countries, you should contact the representative of the marketing authorization holder:
Synthon B.V.
Microweg 22
6545 CM Nijmegen
Netherlands

Date of last revision of the leaflet: