Sunitinib Accord 12.5 mg hard capsules EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Sunitinib Accord 12.5 mg hard capsules EFG

Sunitinib Accord 25 mg hard capsules EFG

Sunitinib Accord 37.5 mg hard capsules EFG

Sunitinib Accord 50 mg hard capsules EFG

sunitinib

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the 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 and works by blocking the activity of a specific group of proteins involved in the growth and proliferation of cancer cells.

Sunitinib Accord is used to treat adults with the following types of cancer:

• Gastrointestinal stromal tumour (GIST), a type of cancer of the stomach and intestine, when imatinib (another anticancer medicine) has failed 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 of the hormone-secreting cells in the pancreas) that have progressed or cannot be surgically removed.

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

2. What you need to know before starting 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

Consult your doctor or pharmacist before starting Sunitinib Accord:

• If you have high blood pressure. Sunitinib Accord may increase blood pressure. Your doctor may monitor your blood pressure during treatment with Sunitinib Accord, and if necessary, you may be treated with medications that lower blood pressure.

• If you have or have had blood disorders, bleeding problems, or bruising. Treatment with Sunitinib Accord may lead to an increased risk of bleeding or cause changes in the number of certain blood cells, which can result in anemia or affect the blood's ability to clot. If you are taking warfarin or acenocoumarol—medications that thin the blood to prevent clots—there may be an increased risk of bleeding. If you experience any bleeding during treatment with Sunitinib Accord, consult your doctor.

• If you have heart problems. Sunitinib Accord may cause heart-related issues. Consult your doctor if you feel very tired, short of breath, or have swollen feet or ankles.

• If you have abnormal heart rhythms. Sunitinib Accord may cause irregularities in heart rhythm. Your doctor may perform electrocardiograms (ECGs) to assess these issues during treatment. Contact your doctor if, during treatment with Sunitinib Accord, you feel dizzy, weak, or experience abnormal heartbeats.

• If you have recently had blood clots in veins and/or arteries (types of blood vessels), including stroke, myocardial infarction, embolism, or thrombosis.

Contact your doctor immediately if you experience symptoms such as chest pain or pressure, arm, back, neck, or jaw pain, shortness of breath, numbness or weakness on one side of the body, difficulty speaking, headache, or dizziness while being treated with Sunitinib Accord.

• If you have or have had an aneurysm (a bulge and weakening in 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, known as thrombotic microangiopathy (TMA). Contact your doctor if you experience fever, fatigue, tiredness, bruising, bleeding, swelling, confusion, vision loss, or seizures.

• If you have or have had thyroid gland problems. Sunitinib Accord may cause thyroid gland disorders. Contact your doctor if you feel unusually tired, feel colder than usual, or develop a deeper voice while taking Sunitinib Accord. Thyroid function should be checked before starting treatment with Sunitinib Accord and periodically during treatment. If your thyroid gland does not produce enough thyroid hormone, you may be treated with replacement thyroid hormone.

• If you have or have had pancreatic or gallbladder disorders. Contact your doctor if you develop 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. Contact your doctor if you develop any of the following signs or symptoms of liver problems during treatment with Sunitinib Accord: itching, yellowing of the eyes or skin, dark urine, or pain or discomfort in the upper right part of the stomach. Your doctor should perform blood tests to monitor liver function before and during treatment with Sunitinib Accord, as well as whenever clinically indicated.

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

• If you are scheduled for surgery or have recently undergone surgery. Sunitinib Accord may affect wound healing. If you are undergoing surgery, you will usually need to stop taking Sunitinib Accord. Your doctor will decide when you can restart treatment.

• Before starting treatment with Sunitinib Accord, you may be advised to have a dental check-up.

• If you have or have had mouth, teeth, and/or jaw pain, swelling or sores in the mouth, numbness or a heavy sensation in the jaw, or loose teeth, inform your doctor and dentist immediately.

• If you require invasive dental treatment or dental surgery, inform your dentist that you are being treated with Sunitinib Accord, especially if you are also receiving or have received intravenous bisphosphonates. Bisphosphonates are medications used to prevent bone complications that may occur due to other medical conditions.

• If you have or have had skin and subcutaneous tissue disorders. During treatment with this medicine, you may develop "pyoderma gangrenosum" (painful skin ulceration) or "necrotizing fasciitis" (a rapidly spreading skin/soft tissue infection that can be fatal). Contact your doctor immediately if you notice signs of infection around a skin lesion, such as fever, pain, redness, swelling, or pus or blood discharge. This reaction is generally reversible upon discontinuation of sunitinib. Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been reported with sunitinib use. These initially appear as red, target-like spots or circular patches, often with central blisters, typically on the trunk. The rash may progress to widespread blistering or skin peeling and can be life-threatening. Seek immediate medical attention if you develop a skin rash or the described skin symptoms.

• If you have or have had seizures. If you have high blood pressure, headache, or vision loss, inform your doctor as soon as possible.

• If you have diabetes. Blood glucose levels in diabetic patients should be monitored regularly to determine whether adjustment of antidiabetic medication is needed to minimize the risk of hypoglycemia. Inform your doctor promptly if you experience signs or symptoms of low blood sugar (fatigue, palpitations, sweating, hunger, or loss of consciousness).

Children and adolescents

Sunitinib Accord is not recommended for use in individuals under 18 years of age.

Other medicines and Sunitinib Accord

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

Some medicines may affect the levels of Sunitinib Accord 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 remedies containing St. John’s wort or hypericum (Hypericum perforatum) – used to treat depression and anxiety

Taking Sunitinib Accord with food and drink

You should avoid drinking grapefruit juice while being treated with Sunitinib Accord.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

If you are able to 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 particular 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; this means it is essentially “sodium-free”.

3. How to take Sunitinib Accord

Follow exactly the instructions given by your doctor for taking this medicine. If you are unsure, consult your doctor again.

Your doctor will determine the correct dose for you depending on the type of cancer being treated. If you are receiving treatment for:

• GIST or RCC: the usual dose is 50 mg once daily for 28 days (4 weeks), followed by a 14-day (2-week) rest period (no medication) in 6-week cycles.
• pNET: the usual dose is 37.5 mg once daily without a rest period.

Your doctor will advise you of the appropriate dose you should take, as well as whether you need to interrupt treatment with Sunitinib Accord and when.

Sunitinib Accord may be taken with or without food.

If you take more Sunitinib Accord than you should

If you have accidentally taken too many capsules, contact your doctor immediately. You may require medical attention.

If you forget to take Sunitinib Accord

Do not take a double dose to make up for missed doses.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

You should contact your doctor immediately if you experience any of the following serious adverse effects (see also section 2: What you need to know before starting to take Sunitinib Accord):

Heart problems. Consult your doctor if you feel very tired, short of breath, or have swollen feet or ankles. These may be symptoms of heart problems, which may include heart failure and problems with the heart muscle (cardiomyopathy).

Lung or breathing problems. Consult your doctor if you develop cough, chest pain, sudden onset of breathing difficulties, or cough up blood. These may be symptoms of a condition called pulmonary embolism, which occurs when blood clots travel to the lungs.

Kidney problems. Consult your doctor if you experience changes in the frequency or absence of urination, as these may be symptoms of kidney failure.

Bleeding. Consult your doctor if you have any of these symptoms or experience a serious bleeding problem during treatment with Sunitinib Accord: painful or swollen stomach (abdomen); vomiting blood; black, tarry stools; blood in urine; headache or any change in mental status; coughing up blood or bloody sputum from the lungs or airways.

Tumour destruction leading to intestinal perforation. Consult your doctor if you have severe abdominal pain, fever, nausea, vomiting, blood in stools, or changes in bowel habits.

Other adverse effects with Sunitinib Accord 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).
• Difficulty breathing.
• High blood pressure.
• Extreme fatigue, loss of strength.
• Rapid swelling of tissues caused by fluid under the skin and around the eye, severe allergic rash.
• Mouth pain/irritation, mouth sores/inflammation/dryness in the mouth, taste disturbances, stomach discomfort, nausea, vomiting, diarrhoea, constipation, abdominal pain/swelling, loss/reduced appetite.
• Decreased activity of the thyroid gland (hypothyroidism).
• Dizziness.
• Headache.
• Nosebleeds.
• Back pain, joint pain.
• Pain in arms and legs.
• Yellowing of the skin/skin discoloration, excessive skin pigmentation, change in hair colour, skin rash on the palms of the hands and soles of the feet, rash, dry skin.
• Cough.
• Fever.
• Difficulty falling asleep.

Common: may affect up to 1 in 10 people

• Blood clots in blood vessels.
• Reduced blood flow 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.
• Complication of a severe infection (infection present in the bloodstream) that may cause tissue damage, organ failure, and death.
• Low blood sugar level (see section 2).
• Loss of protein in urine which may cause swelling.
• Pseudo-flu syndrome.
• Abnormal blood test results, including pancreatic and liver enzymes.
• High level of uric acid in blood.
• Haemorrhoids, rectal pain, bleeding gums, difficulty swallowing or inability to swallow.
• Burning sensation or pain in 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), weakness, muscle fatigue, muscle pain, muscle spasms.
• Dry nose, nasal congestion.
• Excessive tear production.
• Abnormal sensation in the skin, itching, scaly and inflamed skin, blisters, acne, change in nail colour, hair loss.
• Abnormal sensation in the limbs.
• Abnormally decreased/increased sensitivity, especially to touch.
• Indigestion.
• Dehydration.
• Hot flushes.
• Abnormal urine colour.
• Depression.
• Chills.

Uncommon: may affect up to 1 in 100 people

• Potentially life-threatening soft tissue infection, including in the anogenital region (see section 2).
• Stroke.
• Myocardial infarction caused by interruption or reduction of blood flow to the heart.
• Changes in the electrical activity or abnormal heart rhythm.
• Fluid around the heart (pericardial effusion).
• Liver failure.
• Stomach (abdominal) pain caused by inflammation of the pancreas.
• Tumour destruction leading to a hole in the intestine (perforation).
• Inflammation (swelling and redness) of the gallbladder, with or without gallstones.
• Abnormal tube-like connection from one body cavity to another or to the skin.
• Pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw, or loose teeth. These may be signs and symptoms of bone damage in the jaw (osteonecrosis); see section 2.
• Overproduction of thyroid hormones that increase the amount of energy the body uses at rest.
• Problems with wound healing after surgery.
• Elevated blood levels of an enzyme (creatine phosphokinase) from muscle.
• Excessive reaction to an allergen, including pollen allergy, skin rash, skin itching, hives, swelling of body parts, and difficulty breathing.
• Inflammation of the colon (colitis, ischaemic 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).
• Tumour lysis syndrome (TLS) – TLS includes a range of metabolic complications that may occur during cancer treatment. These complications are caused by substances released from dying cancer cells and may include: nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, darkening of urine, and fatigue, associated with abnormal laboratory results (high levels of potassium, uric acid, and phosphate, and low calcium levels in blood), which may lead to changes in kidney function and acute kidney failure.
• Abnormal breakdown of muscles that may lead to kidney problems (rhabdomyolysis).
• Abnormal changes in the brain that may cause a range of symptoms including headache, confusion, seizures, and loss of vision (reversible posterior leukoencephalopathy syndrome).
• Painful skin ulceration (pyoderma gangrenosum).
• Inflammation of the liver (hepatitis).
• Inflammation of the thyroid gland.
• Damage to the smallest blood vessels known as thrombotic microangiopathy (TMA).

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

• Enlargement and weakening of a blood vessel wall or tearing of a blood vessel wall (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 adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Sunitinib Accord

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the packaging, bottle, and blister after CAD or EXP. The expiry date refers to the last day of the month indicated.
• This medicine does not require any special storage conditions.
• Do not use this medicine if the packaging is damaged or shows signs of prior opening.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Sunitinib Accord

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), Iron oxide black (E172) (for 25 mg and 50 mg), Iron oxide red (E172) (for 12.5 mg, 25 mg, 50 mg), Iron oxide yellow (E172) (for 12.5 mg, 25 mg, 50 mg)

- Printing ink: Shellac, Titanium dioxide (E171), Iron oxide black (E172), Propylene glycol, Ammonium hydroxide

Nature of the product and pack contents

Sunitinib Accord 12.5 mg hard capsules

Orange cap and orange body gelatin capsules (approximately 14.3 mm in length) with "12.5 mg" printed in white ink on the body, containing yellow to orange granules.

Sunitinib Accord 25 mg hard capsules

Caramel-coloured cap and orange body gelatin capsules (approximately 15.9 mm in length) with "25 mg" printed in white ink on the body, containing yellow to orange granules.

Sunitinib Accord 37.5 mg hard capsules

Yellow cap and yellow body gelatin capsules (approximately 18.0 mm in length) with "37.5 mg" printed in black ink on the body, containing yellow to orange granules.

Sunitinib Accord 50 mg hard capsules

Caramel-coloured cap and caramel-coloured body gelatin capsules (approximately 19.4 mm in length) with "50 mg" printed in white ink on the body, containing yellow to orange granules.

Sunitinib Accord is available in bottles of 30 capsules and in blister packs of 28 capsules, as well as in unit-dose blister packs of 28 x 1 capsule.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona s/n,

Edifici Est, 6a Planta,

08039, Barcelona,

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 medicinal product, please contact the local representative of the Marketing Authorization Holder:

AT / BE / BG / CY / CZ / DE / DK / EE / ES / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT / NL / NO / PL / PT / RO / SE / SI / SK

Accord Healthcare S.L.U.

Tel: +34 93 301 00 64

EL

Win Medica A.E.

Tel: +30 210 7488 821

Date of the most recent revision of this leaflet: {MM/YYYY}.

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.