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 this 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, consult your doctor, pharmacist or nurse.

-This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.

-If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

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

2.What you need to know before you start taking Sunitinib Accord

3.How to take Sunitinib Accord

4.Possible side effects

5.Storage of Sunitinib Accord

6.Contents of the pack and additional information

Sunitinib Accord contains the active ingredient sunitinib, which is a protein-tyrosine kinase inhibitor. It is used for the treatment of cancer and acts by preventing 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 tumor (GIST), a type of stomach and intestinal cancer, when imatinib (another anticancer medication) has failed 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 tumors (pNET) (tumors of hormone-secreting cells in the pancreas) that have progressed or cannot be removed with surgery.

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

Do not take Sunitinib Accord

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take 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 reduce blood pressure.

-If you have or have had blood disorders, bleeding problems or bruising. Treatment with Sunitinib Accord may lead to a high risk of bleeding or produce changes in the number of certain blood cells, which may cause anemia or affect blood clotting. If you are taking warfarin or acenocoumarol, medications that thin the blood to prevent clots, there may be a greater 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 problems. Consult your doctor if you feel very tired, short of breath, or have swollen feet and ankles.

-If you have abnormal changes in heart rhythm. Sunitinib Accord may cause abnormalities in heart rhythm. Your doctor may obtain electrocardiograms to evaluate these problems during treatment with Sunitinib Accord. Consult your doctor if you feel dizzy, weak, or have abnormal heartbeats during treatment with Sunitinib Accord.

-If you have had recent blood clots in veins and/or arteries (types of blood vessels), including stroke, heart attack, embolism or thrombosis.

Contact your doctor immediately if you experience 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, speech problems, headache or dizziness while being treated with Sunitinib Accord.

-If you have or have had an aneurysm(enlargement and weakening of the wall of a blood vessel) or rupture of the wall of a blood vessel.

-If you suffer or have suffered damage to smaller blood vessels known as microangiopathic thrombosis (MAT). Contact your doctor if you experience fever, fatigue, tiredness, bruises, bleeding, swelling, confusion, loss of vision, and seizures.

-If you have thyroid problems. Sunitinib Accord may cause thyroid problems. Contact your doctor if you feel tired more easily, are generally colder than others, or your voice becomes deeper while taking Sunitinib Accord. Before starting treatment with Sunitinib Accord, your thyroid function should be checked and monitored periodically while taking it. If your thyroid gland does not produce enough thyroid hormone, you may be treated with thyroid hormone replacement.

-If you have pancreatic disorders or gallbladder disorders. Contact your doctor if you develop any of the following signs and symptoms: abdominal pain (upper part of the abdomen), nausea, vomiting, and 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 and symptoms of liver problems during treatment with Sunitinib Accord: itching, yellow eyes or skin, dark urine, and pain or discomfort in the upper right part of the abdomen. Your doctor should perform blood tests to monitor liver function before and during treatment with Sunitinib Accord, as well as when clinically indicated.

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

-If you are to undergo surgery or have had a recent operation. Sunitinib Accord may affect wound healing. If you are to undergo surgery, you will usually stop taking Sunitinib Accord. Your doctor will decide when to start Sunitinib Accord again.

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

-If you have or have had mouth pain, tooth pain, or swelling in the mouth, numbness or a feeling of heaviness in the jaw, or if a tooth has moved, tell your doctor and dentist immediately.

-If you need to have invasive dental treatment or dental surgery, tell your dentist that you are being treated with Sunitinib Accord, particularly if you are also being treated or have been treated with bisphosphonates intravenously. Bisphosphonates are medications used to prevent bone complications that may occur due to another medical condition.

-If you have or have had skin and subcutaneous tissue disorders.During treatment with this medication, you may develop "pyoderma gangrenosum" (painful skin ulceration) or "necrotizing fasciitis" (infection of the skin/soft tissues that spreads quickly and can be fatal). Contact your doctor immediately if you experience symptoms of infection around a skin lesion, such as fever, pain, redness, swelling, or pus or blood discharge. This reaction is usually reversible after stopping sunitinib. Cases of severe skin rash (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been reported, which initially appeared as red spots resembling targets or circular spots, often accompanied by central blisters on the trunk. This rash may progress to form widespread blisters or cause skin peeling, and may be life-threatening. Consult your doctor immediately if you develop a skin rash or the indicated skin symptoms.

-If you have or have had seizures. If you have high blood pressure, headache, or loss of vision, notify your doctor as soon as possible.

-If you have diabetes. Blood glucose levels in diabetic patients should be regularly checked to evaluate if the dose of antidiabetic medication needs to be adjusted to minimize the risk of hypoglycemia. Inform your doctor as soon as possible if you experience signs and symptoms of low blood sugar (fatigue, palpitations, sweating, hunger, and loss of consciousness).

Children and adolescents

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

Other medicines and Sunitinib Accord

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

Some medicines may affect the levels of Sunitinib Accord in your body. You should inform your doctor if you are taking medicines that contain any of the following active ingredients:

•ketoconazole, itraconazole – used to treat fungal infections

•erythromycin, clarithromycin, rifampicin – used to treat infections

•ritonavir – used to treat HIV/AIDS

•dexamethasone – a corticosteroid used to treat various diseases (such as allergic/respiratory disorders or skin diseases)

•phenytoin, carbamazepine, phenobarbital – used to treat epilepsy and other neurological disorders

•herbal medicines containing St. John's Wort or hypericum (Hypericum perforatum)– used to treat depression and anxiety

Taking Sunitinib Accord with food and drinks

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, consult your doctor or pharmacist before using this medicine.

If you can become pregnant, you should use a reliable contraceptive method during treatment with Sunitinib Accord.

If you are breastfeeding, inform your doctor. You should not breastfeed your child during treatment with Sunitinib Accord.

Driving and operating machinery

If you experience dizziness or unusual fatigue, be extra careful 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".

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.

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

− GIST or CCRM: the usual dose is 50 mg once a day for 28 days (4 weeks), followed by 14 days (2 weeks) of rest (no medication) in 6-week cycles.

− pNET: the usual dose is 37.5 mg once a day without a rest period.

Your doctor will indicate the appropriate dose you need to take, as well as whether you need to suspend treatment with Sunitinib Accord and when.

Sunitinib Accord can be taken with or without food.

If you take more Sunitinib Accord than you should

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

If you forgot to take Sunitinib Accord

Do not take a double dose to compensate for the missed doses.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

You should contact your doctor immediately if you experience any of the following serious side 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 and ankles. These may be symptoms of heart problems that can include heart failure and heart muscle problems (cardiomyopathy).

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

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

Bleeding. Consult your doctor if you have any of the following symptoms or a severe bleeding problem during treatment with Sunitinib Accord: stomach (abdomen) pain or swelling; vomit blood; have black, sticky stools; urinate blood; have a headache or any change in mental status; cough up blood or have bloody sputum from the lungs or respiratory tract.

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

Other side effects with Sunitinib Accord may include:

Very common: may affect more than 1 in 10 people

•Reduced platelet, red blood cell, and/or white blood cell count (e.g., neutrophils).

•Difficulty breathing.

•High blood pressure.

•Extreme tiredness, loss of strength.

•Fast swelling of tissues caused by fluid accumulation under the skin and around the eye, severe allergic reaction.

•Mouth pain/irritation, mouth sores/inflammation/dryness, taste disturbances, stomach discomfort, nausea, vomiting, diarrhea, constipation, abdominal pain/swelling, loss/reduced appetite.

•Decreased thyroid gland activity (hypothyroidism).

•Dizziness.

•Headache.

•Nosebleed.

•Back pain, joint pain.

•Arm and leg pain.

•Yellow skin/skin discoloration, excessive skin pigmentation, hair color change, skin rash on palms of hands and soles of 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 obstruction or constriction of coronary arteries.

•Chest pain.

•Decreased heart pumping ability.

•Fluid retention including around the lungs.

•Infections.

•Complication of a severe infection (the infection is present in the bloodstream) that can cause tissue damage, organ failure, and death.

•Low blood sugar (see section 2).

•Protein loss in urine that can cause swelling.

•Pseudogripal syndrome.

•Abnormal blood test results including pancreatic and liver enzymes.

•High uric acid levels in blood.

•Haemorrhoids, rectal pain, gingival bleeding, difficulty swallowing or inability to swallow.

•Burning sensation or pain in the tongue, inflammation of the digestive tract lining, excessive gas in the stomach or intestine.

•Weight loss.

•Musculoskeletal pain (pain in muscles and bones), weakness, muscle fatigue, muscle pain, muscle spasms.

•Runny nose, nasal congestion.

•Excessive tear production.

•Abnormal skin sensation, itching, scaly and inflamed skin, blisters, acne, nail color change, hair loss.

•Abnormal sensation in the extremities.

•Abnormally decreased/increased sensitivity, especially to touch.

•Heartburn.

•Dehydration.

•Hot flashes.

•Abnormal urine color.

•Depression.

•Chills.

Uncommon: may affect up to 1 in 100 people

•Potentially fatal soft tissue infection, including the anogenital region (see section 2).

•Cerebrovascular accident.

•Myocardial infarction caused by interruption or reduction of blood flow to the heart.

•Abnormal heart rhythm or arrhythmia.

•Fluid around the heart (pericardial effusion).

•Liver failure.

•Pancreatitis caused by inflammation of the pancreas.

•Tumor destruction causing intestinal perforation.

•Bile duct inflammation (cholecystitis), associated or not with gallstones.

•Abnormal tube formation like a conduit from a normal body cavity to another body cavity or to the skin.

•Mouth, tooth, and/or jaw pain, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw, or feeling like a tooth is loose. All of these may be signs and symptoms of jaw bone damage (osteonecrosis), see section 2.

•Overproduction of thyroid hormones that increase the amount of energy the body consumes at rest.

•Problems with wound healing after surgery.

•High levels of a muscle enzyme (creatine phosphokinase) in the blood.

•Excessive reaction to an allergen, including pollen allergy, skin rash, itching, urticaria, swelling of body parts, and difficulty breathing.

•Colitis, ischemic 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).

•Tumor lysis syndrome (TLS) - TLS includes a series of metabolic complications that can occur during cancer treatment. These complications are caused by the products released by dying cancer cells and may include: nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, dark urine, and fatigue, associated with abnormal laboratory test results (high potassium, uric acid, and phosphorus levels, and low calcium levels in the blood) that can lead to kidney function changes and acute kidney failure.

•Abnormal muscle breakdown that can lead to kidney problems (rhabdomyolysis).

•Abnormal changes in the brain that can cause a series of symptoms including headache, confusion, seizures, and vision loss (posterior reversible encephalopathy syndrome).

•Painful skin ulceration (pyoderma gangrenosum).

•Liver inflammation (hepatitis).

•Thyroid gland inflammation.

•Damage to small blood vessels known as microangiopathic thrombosis (MAT).

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

•Increased and weakened blood vessel wall or blood vessel wall tear (aneurysms and arterial dissections).

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

-Keep this medication out of the sight and reach of children.

-Do not use this medication after the expiration date that appears on the packaging, the bottle, and the blister pack after CAD or EXP. The expiration date is the last day of the month indicated.

-This medication does not require special storage conditions.

-Do not use this medication if you observe that the packaging is damaged or shows signs of having been opened.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Sunitinib Accord Composition

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

-Capsule content: Microcrystalline cellulose, Mannitol (E421), Sodium croscarmellose, Povidone (E1201), Magnesium stearate

-Capsule coating: Gelatin, Titanium dioxide (E171), Iron oxide black (E172) (For 25 mg and 50 mg), Iron oxide red (E172) (For 12.5 mg, 25 mg, 50mg), Iron oxide yellow (E172) (For 12.5 mg, 25 mg, 50mg)

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

Appearance of the product and contents of the pack

Sunitinib Accord 12.5 mg hard capsules

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

Sunitinib Accord 25 mg hard capsules

Hard gelatin capsules (approximately 15.9 mm in length) with caramel colored cap and orange body and “25 mg” printed in white ink on the body, containing yellow to orange colored granules.

Sunitinib Accord 37.5 mg hard capsules

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

Sunitinib Accord 50 mg hard capsules

Hard gelatin capsules (approximately 19.4 mm in length) with caramel colored cap and caramel colored body and “50 mg” printed in white ink on the body, containing yellow to orange colored granules.

Sunitinib Accord is available in bottles of 30 capsules and blister packs of 28 capsules, and also in single-dose blister packs of 28 x 1 capsules.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona s/n,

Edifici Est, 6aPlanta,

08039, Barcelona,

Spain

Responsible Person

Remedica Ltd.

Aharnon Street, Limassol Industrial Estate,

Building 10, 3056 Limassol,

Cyprus

Pharmacare Premium Ltd.

HHF003 Hal Far Industrial Estate,

Birzebbugia, BBG3000

Malta

Last revision date of this leaflet:{MM/AAAA}.

Detailed information about this medicine is available on the European Medicines Agency website:http://www.ema.europa.eu.