Package leaflet: Information for the user

Sutent 12.5 mg hard capsules, 25 mg hard capsules, 37.5 mg hard capsules, 50 mg hard capsules

sunitinib
Please read all of this leaflet carefully before you start taking this medicine as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not pass it on to others. It may be harmful to persons for whom it was not prescribed, even if their symptoms are the same as yours.
If you experience any side effects, including any not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

What Sutent is and what it is used for
What you need to know before you take Sutent
How to take Sutent
Possible side effects
How to store Sutent
Contents of the pack and other information

1. What Sutent is and what it is used for

Sutent contains the active substance sunitinib, which is a protein kinase inhibitor. It treats cancer by blocking the activity of a specific group of proteins known to be involved in the growth and spread of cancer cells.
Sutent is used to treat adults with the following types of cancer:

Gastrointestinal stromal tumour (GIST), a type of tumour of the stomach and intestine, in cases where imatinib (another anticancer medicine) is no longer effective or can no longer 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 of hormone-producing cells of the pancreas) that are progressing or cannot be surgically removed.

If you have any doubts about how Sutent works or why it has been prescribed for you, consult your doctor.

2. What you should know before taking Sutent

Do not take Sutent

If you are allergic to sunitinib or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before taking Sutent:

If you have high blood pressure. Sutent can cause an increase in blood pressure. Your doctor may monitor your blood pressure during treatment with Sutent and, if necessary, you may need to take medicines to lower your blood pressure.
If you have or have had blood disorders, bleeding problems or bruising. Treatment with Sutent may increase the risk of bleeding and may alter the number of certain blood cells, leading to anaemia or affecting the blood’s ability to clot. The risk of bleeding may be higher if you are taking warfarin or acenocoumarol, medicines that thin the blood to prevent blood clots. Inform your doctor if you experience any bleeding while taking Sutent.
If you have heart problems. Sutent can cause heart-related issues. Inform your doctor if you feel very tired, have shortness of breath, or experience swollen feet or ankles.
If you experience abnormal changes in heart rhythm. Sutent can cause changes in heart rhythm. During treatment with Sutent, your doctor may perform an electrocardiogram (ECG) to assess these changes. Inform your doctor if you feel dizzy, faint, or have irregular heartbeats while being treated with Sutent.
If you have recently had problems due to blood clot formation in veins and/or arteries (types of blood vessels), including stroke, heart attack, embolism, or thrombosis. Contact your doctor immediately if, during treatment with Sutent, you experience symptoms such as chest tightness or pain, pain in the arms, back, neck, or jaw, shortness of breath, numbness or weakness on one side of the body, unsteady gait, headache, or dizziness.
If you have or have had an aneurysm (a bulging 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 small blood vessels called thrombotic microangiopathy (TMA). Inform your doctor if you develop fever, fatigue, tiredness, bruising, bleeding, swelling, mental confusion, vision loss, or seizures.
If you have thyroid problems. Sutent can cause thyroid-related issues. Inform your doctor if, while taking Sutent, you become more easily tired, generally feel colder than others, or your voice becomes lower. Thyroid function should be checked before starting Sutent and regularly during treatment. If your thyroid gland does not produce enough thyroid hormone, you may need to take a thyroid hormone replacement.
If you have or have had pancreas or gallbladder problems. Inform your doctor if you experience any of the following signs and symptoms: stomach pain (upper abdomen), nausea, vomiting, or fever. These may be caused by inflammation of the pancreas or gallbladder.
If you have or have had liver problems. Inform your doctor if, during treatment with Sutent, you develop any of the following signs and symptoms of liver problems: itching, yellowing of the skin or eyes, dark urine, or pain or discomfort in the upper right part of the stomach. Your doctor should perform blood tests to check liver function before and during treatment with Sutent, and as clinically appropriate.
If you have or have had kidney problems. Your doctor will monitor your kidney function.
If you are about to undergo surgery or have recently had an operation. Sutent may affect wound healing. Generally, you will need to stop treatment with Sutent before undergoing surgery. Your doctor will decide when to restart treatment with Sutent.
It is advisable to have a dental check-up before starting treatment with Sutent.
If you have or have had mouth, tooth, and/or jaw pain, swelling or sores in the mouth, numbness or a heavy sensation in the jaw, or tooth loss, inform your doctor and dentist immediately.
If you need to undergo invasive dental treatment or oral surgical procedures, inform your doctor that you are being treated with Sutent, especially if you are also taking or have previously taken intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone complications that may have been prescribed for another clinical condition.
If you have or have had skin and subcutaneous tissue disorders. During treatment with this medicine, conditions such as "pyoderma gangrenosum" (painful skin ulceration) or "necrotising fasciitis" (a rapidly spreading infection of the skin/soft tissue that can be fatal) may occur. Contact your doctor immediately if you develop signs of infection around a skin wound, including fever, pain, redness, swelling, or pus or blood discharge. These events are generally reversible after discontinuation of sunitinib treatment. Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been reported with sunitinib use. These reactions typically start on the trunk as red target-like spots or circular patches, often with blisters in the center. The reaction may progress to widespread blistering or skin peeling and can be fatal. If you develop a skin rash or any of these skin symptoms, consult a doctor immediately.
If you have or have had seizures. Inform your doctor as soon as possible if you experience high blood pressure, headache, or vision loss.
If you have diabetes. Blood sugar levels should be monitored regularly in diabetic patients to determine whether the dosage of diabetes medicines needs adjustment, in order to minimize the risk of low blood sugar. Inform your doctor as soon as possible if you notice signs or symptoms of low blood sugar (fatigue, palpitations, sweating, hunger, or loss of consciousness).

Children and adolescents
Sutent is not indicated for patients under 18 years of age.
Other medicines and Sutent
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription and over-the-counter products.
Some medicines can alter the levels of Sutent in your body. You must 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 AIDS
dexamethasone – a corticosteroid used for various conditions (such as allergic/respiratory disorders or skin diseases)
phenytoin, carbamazepine, phenobarbital – used to treat epilepsy and other neurological conditions
herbal preparations containing St. John’s wort (Hypericum perforatum) – used to treat depression and anxiety

Sutent with food and drink
Grapefruit juice should be avoided during treatment with Sutent.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
If you could become pregnant, you must use a reliable method of contraception during treatment with Sutent.
If you are breastfeeding, inform your doctor. You must not breastfeed during treatment with Sutent.
Driving and using machines
If you experience dizziness or unusual tiredness, exercise particular caution when driving or operating machinery.
Sutent contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per hard capsule, i.e., essentially ‘sodium-free’.

3. How to take Sutent

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor.
Your doctor will prescribe the dose appropriate for you, depending on the type of cancer being treated. If you are being treated for:

GIST or MRCC: the usual dose is 50 mg once daily, taken for 28 days (4 weeks), followed by a 14-day (2-week) rest period (without medication), in 6-week cycles.
pNET: the usual dose is 37.5 mg once daily, without a rest period.

Your doctor will determine the dose required for you and when to stop treatment with Sutent.
Sutent may be taken with or without food.
If you take more Sutent than you should
If you have accidentally taken too many capsules, speak to your doctor immediately. Medical intervention may be necessary.
If you forget to take Sutent
Do not take a double dose to make up for the missed dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if you experience any of the following serious side effects (see also What you need to know before taking Sutent):
Heart problems. Inform your doctor if you feel very tired, have shortness of breath, or have swollen feet and ankles. These could be symptoms of heart problems such as heart failure or problems with the heart muscle (cardiomyopathy).
Lung or breathing problems. Inform your doctor if you develop cough, chest pain, sudden onset of shortness of breath, or coughing up blood. These could be symptoms of pulmonary embolism, which occurs when blood clots reach the lungs.
Kidney problems. Inform your doctor if you notice changes in how often you urinate or if you stop passing urine, which could be symptoms of kidney failure.
Bleeding. Inform your doctor if you experience any of the following symptoms or a severe bleeding problem during treatment with Sutent: swollen, painful stomach (abdomen); vomiting blood; dark, sticky stools; blood in the urine; headache or changes in mental state; coughing up blood or blood-stained sputum from the lungs or airways.
Tumour destruction causing perforation of the intestine. Inform your doctor if you have severe intestinal pain, fever, nausea, vomiting, blood in the stools, or changes in bowel habits.

Other side effects that may occur with Sutent are:
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.
Excessive tiredness, loss of strength.
Swelling due to fluid accumulation under the skin and around the eyes, deep allergic erythema.
Pain/irritation in the mouth, soreness/inflammation/dryness of the mouth, taste disturbances, stomach discomfort, nausea, vomiting, diarrhoea, constipation, abdominal pain/distension, loss/reduced appetite.
Reduced activity of the thyroid gland (hypothyroidism).
Dizziness.
Headache.
Nosebleeds.
Back pain, joint pain.
Pain in the arms and legs.
Yellowing of the skin/changes in skin colour, excessive skin pigmentation, changes in hair colour, rash on the palms of the hands and soles of the feet, skin rash, dry skin.
Cough.
Fever.
Difficulty falling asleep.

Common: may affect up to 1 in 10 people

Blood clot formation in blood vessels.
Inadequate blood supply to the heart muscle due to blockage or narrowing of the coronary arteries.
Chest pain.
Reduced amount of blood pumped by the heart.
Fluid retention, including around the lungs.
Infections.
Complications from severe infections (infection present in the bloodstream) that may lead to tissue damage, organ failure, and death.
Low blood sugar levels (see section 2).
Loss of protein in the urine, which may sometimes lead to swelling.
Flu-like syndrome.
Abnormal blood tests, including levels of liver and pancreatic enzymes.
High levels of uric acid in the blood.
Haemorrhoids, rectal pain, bleeding gums, difficulty swallowing or inability to swallow.
Burning or painful sensation of the tongue, inflammation of the lining of the digestive tract, excess gas in the stomach or intestines.
Weight loss.
Musculoskeletal pain (pain in muscles and bones), muscle weakness, muscle fatigue, muscle pain, muscle spasms.
Dry nose, nasal congestion.
Excessive tearing.
Skin sensitivity changes, itching, skin peeling and inflammation, blister formation, acne, nail discolouration, hair loss.
Abnormal sensations in the extremities.
Excessive reduction/increase in sensitivity, particularly to touch.
Indigestion.
Dehydration.
Hot flushes.
Change in urine colour.
Depression.
Chills.

Uncommon: may affect up to 1 in 100 people

Soft tissue infections, including in the anogenital region, potentially life-threatening (see section 2).
Stroke.
Heart attack caused by interrupted or reduced blood supply to the heart.
Changes in the heart's electrical activity or altered heart rhythm.
Fluid around the heart (pericardial effusion).
Liver failure.
Stomach (abdominal) pain caused by inflammation of the pancreas.
Tumour destruction causing perforation of the intestine.
Inflammation (swelling and redness) of the gallbladder, with or without associated gallstones.
Abnormal passage connecting two body cavities or the skin.
Pain in the mouth, teeth and/or jaw, swelling or irritation in the mouth, numbness or a feeling of heaviness in the jaw, or tooth loss. These could be signs and symptoms of jaw bone damage (osteonecrosis), see section 2.
Excessive production of thyroid hormones leading to increased metabolism.
Problems with wound healing after surgery.
Increased levels of a muscle enzyme in the blood (creatine phosphokinase).
Inappropriate and excessive reaction to allergens, including hay fever, skin rash, skin itching, hives, localized swelling, and breathing difficulties.
Inflammation of the colon (colitis, ischemic colitis).

Rare: may affect up to 1 in 1,000 people

Severe skin and/or mucous membrane reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).
Tumour lysis syndrome (TLS) – TLS includes a set of metabolic complications that may occur during tumour treatment. These are caused by the breakdown products of damaged tumour 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 phosphorus, and low calcium levels in the blood), which may lead to changes in kidney function and acute kidney failure.
Abnormal muscle breakdown that may cause kidney problems (rhabdomyolysis).
Changes in brain function that may lead to a variety of symptoms such as headache, confusion, seizures, and vision loss (reversible posterior leukoencephalopathy syndrome).
Painful skin ulceration (pyoderma gangrenosum).
Inflammation of the liver (hepatitis).
Inflammation of the thyroid gland.
Damage to small blood vessels known as thrombotic microangiopathy (TMA).

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

Abnormal dilation and weakening of the wall of a blood vessel, or a tear in the wall of a blood vessel (aneurysms and arterial dissections).
Lack of energy, confusion, drowsiness, loss of consciousness/coma: these symptoms may be signs of brain toxicity caused by high levels of ammonia in the blood (hyperammonaemic encephalopathy).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sutent

Keep this medicine out of the 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 that month.
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.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Sutent contains
Sutent 12.5 mg hard capsules
The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 12.5 mg of
sunitinib. The other components are:

Capsule contents: mannitol (E421), sodium croscarmellose, povidone (K-25) and magnesium stearate.
Capsule shell: gelatin, red iron oxide (E172) and titanium dioxide (E171).
Ink: shellac, propylene glycol, sodium hydroxide, povidone and titanium dioxide (E171).

Sutent 25 mg hard capsules
The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 25 mg of sunitinib.
The other components are:

Capsule contents: mannitol (E421), sodium croscarmellose, povidone (K-25) and magnesium stearate.
Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172).
Ink: shellac, propylene glycol, sodium hydroxide, povidone and titanium dioxide (E171).

Sutent 37.5 mg hard capsules
The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 37.5 mg of
sunitinib. The other components are:

Capsule contents: mannitol (E421), sodium croscarmellose, povidone (K-25) and magnesium stearate.
Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172).
Ink: shellac, propylene glycol, potassium hydroxide, black iron oxide (E172).

Sutent 50 mg hard capsules
The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 50 mg of sunitinib.
The other components are:

Capsule contents: mannitol (E421), sodium croscarmellose, povidone (K-25) and magnesium stearate.
Capsule shell: gelatin, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172) and black iron oxide (E172).
Ink: shellac, propylene glycol, sodium hydroxide, povidone and titanium dioxide (E171).

Description of the appearance of Sutent and contents of the pack
Sutent 12.5 mg is available as hard gelatin capsules with orange cap and body, marked with “Pfizer” in white ink on the cap and “STN 12.5 mg” on the body, containing yellow/orange granules.
Sutent 25 mg is available as hard gelatin capsules with caramel-coloured cap and orange body, marked with “Pfizer” in white ink on the cap and “STN 25 mg” on the body, containing yellow/orange granules.
Sutent 37.5 mg is available as hard gelatin capsules with yellow cap and body, marked with “Pfizer” in black ink on the cap and “STN 37.5 mg” on the body, containing yellow/orange granules.
Sutent 50 mg is available as hard gelatin capsules with caramel-coloured cap and body, marked with “Pfizer” in white ink on the cap and “STN 50 mg” on the body, containing yellow/orange granules.
Available in bottles of 30 capsules and in perforated unit-dose blisters containing 28 x 1 capsules.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer
Pfizer Italia S.r.l.
Via del Commercio – Zona Industriale
63100 Marino del Tronto (Ascoli Piceno)
Italy

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Luxembourg/Luxemburg Pfizer Luxembourg SARL filialas Lietuvoje
Pfizer NV/SA Tel. + 370 52 51 4000
Tél/Tel: +32 (0)2 554 62 11

България Magyarország
Пфайзер Люксембург САРЛ, Клон България Pfizer Kft.
Тел.: +359 2 970 4333 Tel.: +36-1-488-37-00

Česká republika Malta
Pfizer, spol. s r.o. Vivian Corporation Ltd.
Tel.: +420 283 004 111 Tel: +356 21344610

Danmark Nederland
Pfizer ApS Pfizer BV
Tlf: +45 44 20 11 00 Tel: +31 (0)10 406 43 01

Deutschland Norge
PFIZER PHARMA GmbH Pfizer AS
Tel: +49 (0)30 550055-51000 Tlf: +47 67 52 61 00

Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel.: +372 666 7500 Tel: +43 (0)1 521 15-0

Ελλάδα Polska
Pfizer Ελλάς A.E. Pfizer Polska Sp. z o.o.
Τ  λ: +30 210 6785 800 Tel.: +48 22 335 61 00

España Portugal
Pfizer, S.L. Laboratórios Pfizer, Lda.
Tel: +34 91 490 99 00 Tel: +351 21 423 5500

France România
Pfizer Pfizer Romania S.R.L.
Tél: +33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00

Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL
Tel: + 385 1 3908 777 Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel.: + 386 (0)1 52 11 400

Ireland Slovenská republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: 1800 633 363 (toll free) Tel.: + 421 2 3355 5500
+44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Sími: +354 540 8000 Puh./Tel: +358 (0)9 43 00 40

Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: +46 (0)8 550 520 00

Kύπρος United Kingdom (Northern Ireland)
Pfizer Ελλάς A.E. (Cyprus Branch) Pfizer Limited
Tηλ.:+ 357 22 817690 Tel: +44 (0) 1304 616161

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel.: + 371 670 35 775

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND REASONS FOR THE VARIATION OF THE TERMS OF THE
MARKETING AUTHORISATION(S)

SCIENTIFIC CONCLUSIONS
Taking into account the assessment by the Pharmacovigilance Risk Assessment Committee (PRAC) of the Periodic Safety Update Report(s) (PSUR) for sunitinib, the PRAC's scientific conclusions are as follows:
In view of available data on the risk of hyperammonaemic encephalopathy from the literature and spontaneous reports, which in some cases include a close temporal relationship, a de-challenge and/or a positive re-challenge, the PRAC considers that a causal relationship between sunitinib and hyperammonaemic encephalopathy is at least a reasonable possibility. The PRAC concluded that the product information for medicinal products containing sunitinib should therefore be amended accordingly.
Following review of the PRAC recommendation, the Committee for Medicinal Products for Human Use (CHMP) agrees with the overall conclusions and reasoning of the PRAC recommendation.

Reasons for the variation of the terms of the marketing authorisation(s)
Based on the scientific conclusions for sunitinib, the CHMP considers that the benefit-risk balance of the medicinal product(s) containing sunitinib remains unchanged, subject to the proposed amendments to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation(s).