Sunitinib Sinthon

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

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

• 1. What Sunitinib Synthon is and what it is used for
• 2. Before you take 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 to treat cancer. It works by inhibiting the activity of certain proteins made by the body that are involved in the growth and spread of cancer cells.

Sunitinib Synthon is used to treat the following types of cancer in adults:

• gastrointestinal stromal tumour (GIST), a type of cancer of the stomach and intestines, when imatinib (another cancer medicine) is no longer effective or cannot be taken;
• metastatic renal cell carcinoma (MRCC), a type of kidney cancer that has spread to other parts of the body;
• pancreatic neuroendocrine tumours (pNET), cancers that start in the hormone-producing cells of the pancreas, which are advanced or cannot be surgically removed.

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

2. Before you take Sunitinib Synthon

Do not take Sunitinib Synthon

• 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 Synthon, tell your doctor:

• If you have high blood pressure. Sunitinib Synthon may increase your blood pressure. Your doctor may check your blood pressure during treatment with Sunitinib Synthon and you may need to take medicine to lower your blood pressure.
• If you have or have had bleeding problems or blood clots. Treatment with Sunitinib Synthon may increase the risk of bleeding or changes in certain blood cells, which can cause anaemia or affect the blood's ability to clot. If you are taking warfarin or acenocoumarol, medicines that thin the blood to prevent blood clots, there may be a higher risk of bleeding. Tell your doctor about any bleeding during treatment with Sunitinib Synthon.
• If you have heart problems. Sunitinib Synthon may cause heart problems. Tell your doctor if you feel very tired, have shortness of breath, or swelling of your feet or ankles.
• If you have irregular heartbeats. Sunitinib Synthon may cause irregular heartbeats. Your doctor may perform an electrocardiogram to check for these irregularities during treatment with Sunitinib Synthon. Tell your doctor if you feel dizzy, faint, or have irregular heartbeats during treatment with Sunitinib Synthon.
• If you have recently had problems with blood clots in your veins and/or arteries (types of blood vessels), including stroke, heart attack, blockage, or blood clots. Tell 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 a condition called thrombotic microangiopathy (a condition that affects the smallest blood vessels). Tell your doctor if you experience fever, fatigue, tiredness, bruising, bleeding, swelling, confusion, loss of vision, or seizures.
• If you have thyroid problems. Sunitinib Synthon may cause thyroid problems. Tell your doctor if you feel tired, feel colder than others, or have a hoarse voice during treatment with Sunitinib Synthon. Your doctor should check your thyroid function before starting treatment with Sunitinib Synthon 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 pancreas 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 or have had liver problems. Tell your doctor if you experience any of the following symptoms of liver problems during treatment with Sunitinib Synthon: 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 Synthon, during treatment, and if there are any signs of liver 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 stopped 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 mouth pain, toothache, jaw pain or swelling, mouth sores, numbness or heaviness of the jaw, or tooth loosening, tell your oncologist and dentist immediately.
• If you need to have invasive dental procedures or dental surgery, tell 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 that may be taken for another condition.
• If you have or have had skin and subcutaneous tissue disorders. During treatment with this medicine, pyoderma gangrenosum (painful skin ulcers) or necrotizing fasciitis (a rapidly spreading infection of the skin and/or soft tissues that can be life-threatening) may occur. Tell 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 conditions usually resolve after stopping sunitinib treatment. During sunitinib treatment, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed, which initially appear as red patches with a target-like shape or round patches, often with centrally located blisters. The rash may develop into widespread blisters or peeling of the skin and can be life-threatening. If you experience a rash or the above-mentioned skin symptoms, tell 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 immediately if you experience symptoms of 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 with other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, including those obtained without a prescription and those you plan to take.

Some medicines may affect the levels of Sunitinib Synthon in your body. Tell your doctor if you are taking medicines that contain 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

Do not drink grapefruit juice while taking Sunitinib Synthon.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, 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 Synthon.

Do not breast-feed while taking Sunitinib Synthon.

Driving and using machines

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

Sunitinib Synthon contains sodium

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

3. How to take Sunitinib Synthon

Always take this medicine exactly as your doctor has told you. If you are not sure, check with your doctor.

Your doctor will prescribe the dose that is right for you, depending on the type of cancer you have.

• 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 taking the medicine), in 6-week cycles of treatment.
• For pNET: the usual dose is 37.5 mg taken once a day continuously.

Your doctor will determine the right dose for you and when to stop taking Sunitinib Synthon.

Sunitinib Synthon can be taken with or without food.

To open the blisters, separate one dose from the blister using the perforation, then peel off the foil from the blister and remove the capsule. Do not push the capsule through the foil as this may damage the capsule.

If you take more Sunitinib Synthon than you should

If you have taken too many capsules, contact your doctor immediately.

Medical attention may be necessary.

If you forget to take Sunitinib Synthon

Do not take a double dose to make up for a forgotten dose.

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 side effects (see also section 2, "Before you take Sunitinib Synthon"):

• heart problems. Tell your doctor if you feel very tired, have shortness of breath, or swelling of your feet or ankles. These may be symptoms of heart problems, which can include heart failure and problems with the heart muscle (cardiomyopathy).
• lung or breathing problems. 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 travel to the lungs.
• kidney problems. Tell your doctor if you experience changes in urination or lack of urination, which may be symptoms of kidney failure.
• bleeding. 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, tarry stools; blood in urine; headache or changes in consciousness; coughing up blood or bloody sputum from the lungs or airways.
• tumour lysis syndrome 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 Synthon may include:

Very common(may affect more than 1 in 10 people)

• reduced number of platelets, red blood cells, and/or white blood cells (e.g. neutrophils)
• shortness of breath
• high blood pressure
• extreme tiredness, loss of strength
• swelling caused by fluid accumulation under the skin and around the eyes, allergic rash, deep
• mouth pain, toothache, and/or jaw pain, mouth sores, numbness or heaviness of the jaw, or tooth loosening
• reduced 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 colour changes, palmar-plantar erythrodysesthesia (hand-foot syndrome), rash, dry skin
• coughing
• fever
• difficulty sleeping

Common(may affect up to 1 in 10 people)

• blood clots in blood vessels
• insufficient 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 accumulation, including in the lungs
• infections
• complication after severe infection (sepsis), which can cause tissue damage, organ failure, and death
• low blood sugar levels (see section 2, "Before you take Sunitinib Synthon").
• protein in the 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, anal pain, gum bleeding, difficulty swallowing, or loss of ability to swallow
• tongue pain or burning sensation, inflammation of the mucous membranes, painful mouth sores, and/or inflammation, and/or dry mouth, taste disturbances, stomach upset, nausea, vomiting, diarrhoea, constipation, abdominal pain and/or swelling, loss of and/or decreased appetite
• 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
• disturbances of skin sensation
• disturbances related to increased or decreased sensitivity, especially to touch
• heartburn
• dehydration
• hot flushes
• abnormal urine colour
• depression
• chills

Uncommon(may affect up to 1 in 100 people)

• life-threatening infection of soft tissues, including the perineal area (see section 2, "Before you take Sunitinib Synthon").
• stroke
• heart attack caused by interruption or narrowing of the coronary arteries
• changes in heart rhythm or electrical activity.
• fluid accumulation around the heart (pericardial effusion)
• liver failure
• stomach pain (abdomen) caused by pancreatitis
• tumour lysis syndrome 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, toothache, and/or jaw pain, mouth sores, numbness or heaviness of the jaw, or tooth loosening. These may be symptoms of jawbone damage (osteonecrosis), see section 2, "Before you take Sunitinib Synthon".
• excessive production of thyroid hormones leading to increased resting metabolism
• impaired 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 any part of the body, 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, 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, low urine output, 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 damage 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)
• liver inflammation
• thyroid inflammation
• 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 tear in the wall of a blood vessel (aneurysm and arterial dissection)

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 national reporting system listed below.

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 which is stated on the carton, container, and blister after EXP. The expiry date refers to the last day of that month.

Store in the original package 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 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. These 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 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 is sunitinib. Each hard capsule contains sunitinib malate equivalent to 25 mg of sunitinib.

The 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 is sunitinib. Each hard capsule contains sunitinib malate equivalent to 50 mg of sunitinib.

The 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 orange cap and orange body, with white printing "SNB" and "12.5" on the body.

The capsule is filled with orange powder. Capsule size: 4 (length approximately 14 mm).

[Sunitinib Synthon, 25 mg, hard capsules]

Sunitinib Synthon 25 mg: hard capsule (capsule) with caramel (light brown) cap and orange body, with white printing "SNB" and "25" on the body.

The capsule is filled with orange powder. Capsule size: 3 (length approximately 16 mm).

[Sunitinib Synthon, 50 mg, hard capsules]

Sunitinib Synthon 50 mg: hard capsule (capsule) with caramel cap and caramel (light brown) body, with black printing "SNB" and "50" on the body.

The capsule is filled with orange powder. Capsule size: 1EL (elongated; length approximately 20 mm).

The medicine is available in HDPE plastic containers with 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 Authorisation Holder and Manufacturer

Marketing Authorisation 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

For more information on the names of the medicinal products in other EU member states, please contact the representative of the Marketing Authorisation Holder:

Synthon B.V.

Microweg 22

6545 CM Nijmegen

Netherlands

Date of last revision of the leaflet