Sunitinib Accord

Patient Information Leaflet: Information for the User

Sunitinib Accord 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 taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

1. What Sunitinib Accord is and what it is used for
2. What you need to know before taking Sunitinib Accord
3. How to take Sunitinib Accord
4. Possible side effects
5. How to store Sunitinib Accord
6. Contents of the pack and other information

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

Sunitinib Accord contains the active substance sunitinib, which is a protein kinase inhibitor. It is
used to treat cancer by inhibiting the activity of a specific group of proteins known to be
involved in the growth and spread of cancer cells. Sunitinib Accord 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 taken.
• Metastatic renal cell carcinoma (MRCC), a type of kidney cancer that has spread to other parts of the body.
• Progressive or non-resectable pancreatic neuroendocrine tumours (pNET) (tumours of the hormone-producing cells of the pancreas).

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

2. What you should know before taking Sunitinib Accord

Do not take Sunitinib Accord

• 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 or pharmacist before taking Sunitinib Accord:

• If you have high blood pressure. Sunitinib Accord may cause an increase in blood pressure. Your doctor may monitor your blood pressure during treatment with Sunitinib Accord and, if necessary, prescribe medication to lower your blood pressure.
• If you have or have had blood disorders, bleeding problems or bruising. Treatment with Sunitinib Accord may increase the risk of bleeding, changes in the number of certain blood cells (whose deficiency may lead to anaemia) or affect 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 Sunitinib Accord.
• If you have heart problems. Sunitinib Accord may 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. Sunitinib Accord may cause changes in heart rhythm. During treatment with Sunitinib Accord, your doctor may perform an electrocardiogram (ECG) to assess these changes. Inform your doctor if you feel dizzy, faint, or experience irregular heartbeats while being treated with Sunitinib Accord.
• 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 Sunitinib Accord, 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 weakened and dilated blood vessel wall) or a tear in the wall of a blood vessel.
• If you have or have had damage to small blood vessels known as thrombotic microangiopathy (TMA). Inform your doctor if you notice symptoms such as fever, fatigue, tiredness, bruising, bleeding, swelling, mental confusion, vision loss, or seizures.
• If you have thyroid problems. Sunitinib Accord may cause thyroid-related issues. Inform your doctor if, while taking Sunitinib Accord, you feel unusually tired, feel colder than others, or your voice becomes deeper. Thyroid function should be checked before starting and regularly during treatment with Sunitinib Accord. If your thyroid 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 or 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 Sunitinib Accord, you experience any of the following signs or 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 Sunitinib Accord, 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 surgery. Sunitinib Accord may affect how wounds heal. Generally, you should stop treatment with Sunitinib Accord before undergoing surgery. Your doctor will decide when to restart treatment.
• It is advisable to have a dental check-up before starting treatment with Sunitinib Accord.
• If you have or have had mouth, tooth, and/or jaw pain, swelling or sores in the mouth, numbness or a feeling of heaviness in the jaw, or tooth loss, inform your doctor and dentist immediately.
• If you need to undergo invasive dental treatment or oral surgery, inform your doctor that you are being treated with Sunitinib Accord, 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 medical 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 "necrotizing fasciitis" (a rapidly spreading and potentially fatal infection of the skin/soft tissue) may occur. Contact your doctor immediately if you experience signs of infection around a skin wound, including fever, pain, redness, swelling, or pus or blood drainage. These events are generally reversible after stopping sunitinib treatment. Serious skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been reported with sunitinib use. These reactions typically begin on the trunk as red, target-shaped 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 doses of diabetes medications need 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
Sunitinib Accord is not indicated for patients under 18 years of age.

Other medicines and Sunitinib Accord
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Some medicines can alter the levels of Sunitinib Accord in your body. You must inform your doctor if you are taking medicines containing 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

Sunitinib Accord with food and drink
Grapefruit juice should be avoided during treatment with Sunitinib Accord.

Pregnancy and breastfeeding
If you are pregnant, suspect 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 Sunitinib Accord.
If you are breastfeeding, inform your doctor. You must not breastfeed during treatment with Sunitinib Accord.

Driving and using machines
If you experience dizziness or unusual tiredness, exercise caution when driving or operating machinery.

Sunitinib Accord contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium (sodium croscarmellose) per capsule, i.e., essentially "sodium-free".

3. How to take Sunitinib Accord

Take this medicine exactly as your doctor has told you. If you are unsure, 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 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 Sunitinib Accord. Sunitinib Accord may be taken with or without food.
If you take more Sunitinib Accord than you should
If you accidentally take too many capsules, speak to your doctor immediately. Medical intervention may be necessary.
If you forget to take Sunitinib Accord
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 (also see section 2 What you need to know before taking Sunitinib Accord):

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 experience 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 serious bleeding problem during treatment with Sunitinib Accord: swollen, painful stomach (abdomen); vomiting blood; dark, sticky stools; blood in the urine; headache or changes in mental state; coughing up blood or bloody phlegm 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 Sunitinib Accord 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 retention under the skin and around the eyes, deep allergic rash.
• Pain/irritation in the mouth, soreness/inflammation/dryness of the mouth, altered taste, stomach discomfort, nausea, vomiting, diarrhoea, constipation, abdominal pain/swelling, 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) which may cause 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 (muscle and bone pain), muscle weakness, muscle fatigue, muscle pain, muscle spasms.
• Dry nose, nasal congestion.
• Excessive tearing.
• Skin sensitivity changes, itching, skin peeling and inflammation, blistering, 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 connecting a cavity to 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.

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 cancer treatment. These are caused by the breakdown products of affected tumour cells and may include: nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine and fatigue, associated with abnormal laboratory test results (elevated levels of potassium, uric acid and phosphoric acid, and low calcium levels in the blood), which may lead to changes in kidney function and acute kidney failure.
• Abnormal breakdown of muscle tissue that may cause kidney problems (rhabdomyolysis).
• Changes in brain function that may lead to a variety of symptoms such as headache, confusion, seizures and loss of vision (reversible posterior leucoencephalopathy 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):

• Enlargement 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 get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
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 Sunitinib Accord

• 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, bottle, and blister after “Exp.” or “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 you no longer use. This will help protect the environment.

6. Package contents and other information

What Sunitinib Accord contains
The active substance is sunitinib. Each hard capsule contains 12.5 mg, 25 mg, 37.5 mg, or 50 mg of sunitinib. The other components are:

• Capsule contents: microcrystalline cellulose, mannitol (E421), sodium croscarmellose, povidone (E1201), magnesium stearate.
• Capsule shell: gelatin, titanium dioxide (E171), black iron oxide (E172) (for 25 mg and 50 mg), red iron oxide (E172) (for 12.5 mg, 25 mg, 50 mg), yellow iron oxide (E172) (for 25 mg, 37.5 mg, 50 mg).
• Printing ink: shellac, titanium dioxide (E171), black iron oxide (E172), propylene glycol, ammonium hydroxide.

Description of the appearance of Sunitinib Accord and package contents
Sunitinib Accord 12.5 mg hard capsules
Gelatin capsules (approximate length 14.3 mm) with orange cap and body, printed with “12.5 mg” in white ink on the body, containing yellow/orange granules.
Sunitinib Accord 25 mg hard capsules
Gelatin capsules (approximate length 15.9 mm) with caramel-colored cap and orange body, printed with “25 mg” in white ink on the body, containing yellow/orange granules.
Sunitinib Accord 37.5 mg hard capsules
Gelatin capsules (approximate length 18.0 mm) with yellow cap and body, printed with “37.5 mg” in black ink on the body, containing yellow/orange granules.
Sunitinib Accord 50 mg hard capsules
Gelatin capsules (approximate length 19.4 mm) with caramel-colored cap and body, printed with “50 mg” in white ink on the body, containing yellow/orange granules.
Sunitinib Accord is available in bottles containing 30 capsules, blisters containing 28 capsules, and unit-dose blisters containing 28 x 1 capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll De Barcelona s/n,
Edifici Est, 6 Planta,
Barcelona, 08039,
Spain

Manufacturer
Remedica Ltd.
Aharnon Street, Limassol Industrial Estate,
Building 10, 3056 Limassol,
Cyprus
Pharmacare Premium Ltd.
HHF003 Hal Far Industrial Estate,
Birzebbugia, BBG3000
Malta

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
AT / BE / BG / CY / CZ / DE / DK / EE / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT / NL / NO / PT / PL / RO / SE / SI / SK / ES
Accord Healthcare S.L.U.
Tel: +34 93 301 00 64
EL
Win Medica A.E.
Tel: +30 210 7488 821

Other sources of information
More detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu.