Sunitinib synthon

Package leaflet: Information for the user

Sunitinib Synthon, 12.5 mg, hard capsules
Sunitinib Synthon, 25 mg, hard capsules
Sunitinib Synthon, 50 mg, hard capsules
Sunitinib
Please read this leaflet carefully before taking this medicine, because it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor. See section 4.

Table of contents of the leaflet

1. What Sunitinib Synthon is and what it is 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 pack and other information

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

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

• Gastrointestinal stromal tumours (GIST), a type of stomach and intestinal tumour, when imatinib (another anticancer medicine) is no longer effective 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 Synthon works or why this medicine has been prescribed, please 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 treatment with Sunitinib Synthon, discuss the following with your doctor:

• If you have or have had high blood pressure. Sunitinib Synthon may increase blood pressure. Your doctor may monitor your blood pressure during treatment with Sunitinib Synthon, and you may need to be treated with antihypertensive medicines if necessary.

• If you have or have had blood disorders, bleeding, or bruising. Treatment with Sunitinib Synthon may increase the risk of bleeding or may cause changes in certain blood cells, which could 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, your risk of bleeding may be higher. Inform your doctor about any bleeding that occurs during treatment with Sunitinib Synthon.

• If you have heart problems. Sunitinib Synthon may cause heart-related issues. Inform your doctor if you experience unusual fatigue, shortness of breath, or swelling in your feet or ankles.

• If you have heart rhythm disorders. Sunitinib Synthon may cause irregular heart rhythms. Your doctor may perform an electrocardiogram (ECG) during treatment to monitor for such disturbances. Inform your doctor if you experience dizziness, fainting, or irregular heartbeat while taking Sunitinib Synthon.

• If you have recently had venous or arterial thrombotic events (types of blood vessels), including stroke, myocardial infarction, pulmonary embolism, or thrombophlebitis. Contact your doctor immediately if you develop symptoms such as chest pain or pressure, pain in the arms, back, neck, or jaw, shortness of breath, numbness or weakness on one side of the body, difficulty speaking, headache, or dizziness during treatment with Sunitinib Synthon.

• If you have or have had an aneurysm (a weakened and enlarged blood vessel wall) or arterial dissection (tearing of the blood vessel wall).

• If you have or have had damage to the smallest blood vessels known as thrombotic microangiopathy. Inform your doctor if you develop fever, fatigue, weakness, bruising, bleeding, swelling, confusion, vision loss, or seizures.

• If you have or have had thyroid problems. Sunitinib Synthon may affect thyroid function. Inform your doctor if you feel unusually tired, feel colder than usual, or experience voice changes during treatment with Sunitinib Synthon. Your doctor should check your thyroid function before starting treatment and regularly during therapy. If your thyroid does not produce enough thyroid hormone, you may require thyroid hormone replacement therapy.

• If you have or have had pancreas or gallbladder disorders. Inform your doctor if you experience any of the following symptoms: stomach pain (upper abdomen), nausea, vomiting, or fever. These may be signs of pancreatitis or gallbladder inflammation.

• If you have or have had liver problems. Inform your doctor if you develop any of the following signs of liver dysfunction during treatment with Sunitinib Synthon: itching, yellowing of the eyes or skin (jaundice), dark-coloured urine, or pain or discomfort in the right upper abdomen. Your doctor should order blood tests to monitor liver function before starting treatment, during therapy, and whenever clinically indicated.

• If you have or have had kidney problems. Your doctor will monitor kidney function.

• If you are scheduled for surgery or have recently undergone surgery. Sunitinib Synthon may impair wound healing. Sunitinib Synthon is usually discontinued before surgical procedures. Your doctor will decide when to restart treatment.

• A dental examination is recommended before starting treatment with Sunitinib Synthon:

• 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 Synthon, especially if you are also taking or have taken intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone problems and may be taken for other conditions.

• If you have or have had skin and 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 you develop signs of infection around skin lesions, including fever, pain, redness, swelling, or discharge of pus or blood. These conditions usually resolve after discontinuation of sunitinib. Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed during sunitinib treatment. These initially appear as red, target-shaped or circular skin lesions, 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 any of the above-mentioned skin symptoms, contact your doctor 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 determine whether adjustment of antidiabetic medication is needed to minimize the risk of hypoglycaemia. Inform your doctor promptly if you experience symptoms of low blood sugar (fatigue, palpitations, excessive sweating, hunger, or loss of consciousness).

Children and adolescents
Sunitinib Synthon is not recommended for patients under 18 years of age.
Sunitinib Synthon and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription, as well as any medicines you plan to take.
Some medicines may affect the concentration of Sunitinib Synthon in the 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 conditions (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 Synthon with food and drink
Do not drink grapefruit juice while taking Sunitinib Synthon.
Pregnancy and breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using this medicine.
Women of childbearing potential should use an effective method of contraception during treatment with Sunitinib Synthon.
Women who are breastfeeding should inform their doctor. Breastfeeding is not recommended during treatment with Sunitinib Synthon.
Driving and using machines
Exercise caution when driving or operating machinery if you experience dizziness or significant fatigue.
Sunitinib Synthon contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. this medicine is considered "sodium-free".

3. How to take Sunitinib Synthon

This medicine should always be taken as prescribed by your doctor. If in doubt, consult your doctor.
Your doctor will prescribe the dose appropriate for the individual patient, depending on the type of tumour. 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 (without medication), 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 the individual patient and the time to stop treatment with Sunitinib Synthon.
Sunitinib Synthon may be taken with or without food.
To open the blister, peel off a single dose along the tear line. Then peel back the foil from the blister and remove the capsule. Do not push the capsule through the foil, as this may damage the capsule.

Taking more Sunitinib Synthon than prescribed
If too many capsules have been taken, contact your doctor immediately.
Medical intervention may be necessary.
Missing a dose of Sunitinib Synthon
Do not take a double dose to make up for a missed dose.

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 adverse reactions (see also Important information before taking Sunitinib Synthon):

• heart problems. Inform 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 problems with the heart muscle (cardiomyopathy).
• lung or breathing problems. Inform 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. Inform the doctor if the patient experiences changes in frequency or absence of urination, which may be symptoms of kidney failure.
• bleeding. Inform the doctor if the patient experiences any of the following symptoms or severe bleeding while being treated with Sunitinib Synthon: 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.
• tumor lysis leading to intestinal perforation. Inform the doctor if the patient experiences severe abdominal pain, fever, nausea, vomiting, blood in the stool, or changes in bowel function.

Other adverse reactions with Sunitinib Synthon 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
• 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, rash on palms and soles, rash, dry skin
• cough
• fever
• difficulty sleeping

Common (may affect less than 1 in 10 people)

• blood clots in blood vessels
• inadequate blood supply to the heart due to blockage or narrowing of the coronary arteries
• chest pain
• reduced amount of blood pumped by the heart
• fluid retention, including in the lung area
• infections
• complication following severe infection (blood infection), which may lead to tissue damage, organ failure, and death
• decreased 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
• haemorrhoids, rectal pain, gum bleeding, difficulty swallowing or loss of swallowing ability
• burning or painful sensation of the tongue, inflammation of the mucous membrane 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 mucous membrane, sensation of nasal congestion
• excessive tearing
• skin sensation disorders, 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 less than 1 in 100 people)

• life-threatening soft tissue infections, including the anogenital area (see section 2, “Important information before taking Sunitinib Synthon”).
• stroke
• myocardial infarction caused by interruption or reduction of blood supply to the heart
• changes in electrical function or rhythm disturbances of the heart
• presence of fluid around the heart (pericardial effusion)
• liver failure
• abdominal pain due to inflammation of the pancreas
• tumor 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 in the jaw, or loose teeth. These may be symptoms of jaw bone 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 muscle enzyme (creatine kinase) in 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 less than 1 in 1000 people)

• severe reaction affecting the skin and (or) mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme)
• tumor lysis syndrome, a group of metabolic complications that may occur during cancer treatment. These complications are caused by products from the breakdown of dying tumor 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 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 which may cause a syndrome of symptoms including headache, confusion, seizures, and vision loss (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 blood vessel wall or rupture of the blood vessel wall (aneurysm and arterial dissection)

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform the doctor. 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 responsible entity.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Sunitinib Synthon

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.
This medicine does not require any special storage temperature conditions.
Do not use this medicine if you notice that the packaging is damaged or if there are signs of prior opening.
Medicines must not be disposed of via household waste or waste bins. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

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

• Capsule contents: 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 is sunitinib. Each hard capsule contains sunitinib malate equivalent to
25 mg of sunitinib.
The other ingredients are:

• Capsule contents: 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 is sunitinib. Each hard capsule contains sunitinib malate equivalent to
50 mg of sunitinib.
The other ingredients are:

• Capsule contents: 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: hard gelatin capsule (capsule) with an orange cap and an orange body, printed with white markings: “SNB” and “12.5” on the body. The capsule is filled with orange powder. Capsule size: 4 (approximately 14 mm in length).
[Sunitinib Synthon, 25 mg, hard capsules]
Sunitinib Synthon 25 mg: hard gelatin capsule (capsule) with a caramel (light brown) cap and an orange body, printed with white markings: “SNB” and “25” on the body. The capsule is filled with orange powder. Capsule size: 3 (approximately 16 mm in length).
[Sunitinib Synthon, 50 mg, hard capsules]
Sunitinib Synthon 50 mg: hard gelatin capsule (capsule) with a caramel cap and a caramel (light brown) body, printed with black markings “SNB” and “50” on the body. The capsule is filled with orange powder. Capsule size: 1EL (elongated; approximately 20 mm in length).
The medicine is available in HDPE plastic bottles with a child-resistant PP 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 unit dose blisters containing 28 x 1 or 30 x 1 capsules in a cardboard box.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Synthon B.V., Microweg 22, 6545 CM Nijmegen, The Netherlands
Manufacturer:
Synthon Hispania S.L., Calle De Castello 1, Poligono Las Salinas, 08830 Sant Boi de Llobregat,
Spain
For further information on the product names in other countries of the European Economic Area, please contact the representative of the Marketing Authorisation Holder:
Synthon B.V.
Microweg 22
6545 CM Nijmegen
The Netherlands