SUNITINIB ACCORD 25 mg HARD CAPSULES

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 all of this leaflet carefully before you start 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, pharmacist, or nurse.
• 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

Sunitinib Accord contains the active substance sunitinib, which is a protein kinase inhibitor. It is used to treat cancer and works by preventing the activity of a special 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 intestine cancer, when imatinib (another anti-cancer medicine) has failed or when imatinib 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 the hormone-producing cells in the pancreas) that have progressed or cannot be removed by surgery.

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

2. What you need to know before you take Sunitinib Accord

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

Tell your doctor or pharmacist before you start taking Sunitinib Accord:

• If you have high blood pressure. Sunitinib Accord may increase your blood pressure. Your doctor may check your blood pressure during treatment with Sunitinib Accord and, if necessary, treat you with medicines that lower 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 changes in the number of certain blood cells, which can cause anemia or affect the blood's ability to clot. If you are taking warfarin or acenocoumarol, medicines that thin the blood to prevent clots, there may be a higher 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. Tell your doctor if you feel very tired, short of breath, or if your feet and ankles are swollen.
• If you have changes in your heart rhythm. Sunitinib Accord may cause changes in your heart rhythm. Your doctor may perform electrocardiograms to evaluate these problems during treatment with Sunitinib Accord. Tell your doctor if you feel dizzy, weak, or have irregular 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.

Tell your doctor immediately if you experience symptoms such as chest pain or pressure, pain in your arms, back, neck, or jaw, shortness of breath, numbness or weakness on one side of your body, speech problems, headache, or dizziness while taking Sunitinib Accord.

• If you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in the wall of a blood vessel.

• If you have or have had damage to the small blood vessels, known as thrombotic microangiopathy (TMA). Tell your doctor if you experience fever, fatigue, tiredness, bruising, bleeding, swelling, confusion, vision loss, or seizures.

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

• If you have or have had pancreatic or gallbladder disorders. Tell your doctor if you develop any of the following signs and symptoms: stomach pain (upper abdomen), nausea, vomiting, and fever. These may be caused by inflammation of the pancreas or gallbladder.

• If you have or have had liver problems. Tell 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 side of the stomach. Your doctor should perform blood tests to monitor your 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 kidney function.

• If you are going to have surgery or have had a recent operation. Sunitinib Accord may affect wound healing. If you are going to have an operation, 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 pain in your mouth, teeth, and/or jaw, swelling, or ulcers inside your mouth, numbness, or a feeling of heaviness in your jaw, or if you have loose teeth, tell your doctor and dentist immediately.
• If you need to have invasive dental treatment or dental surgery, tell your dentist that you are taking Sunitinib Accord, especially if you are also being treated with intravenous bisphosphonates. Bisphosphonates are medicines 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 medicine, "pyoderma gangrenosum" (painful skin ulceration) or "necrotizing fasciitis" (rapidly spreading skin/soft tissue infection that can be fatal) may occur. Tell your doctor immediately if you experience symptoms of infection around a skin lesion, such as fever, pain, redness, swelling, or discharge of pus or blood. This reaction is usually reversible after stopping sunitinib. There have been reports of severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) associated with sunitinib use, which initially appeared as red patches resembling targets or circular patches, often accompanied by central blisters on the trunk. This rash may progress to widespread blisters or peel, and can be life-threatening. Tell your doctor immediately if you develop a skin rash or the skin symptoms indicated.

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

• If you have diabetes. Your blood sugar levels should be regularly checked to assess whether it is necessary to adjust the dose of your anti-diabetic medicine to minimize the risk of low blood sugar. Tell 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 children and adolescents under 18 years of age.

Other medicines and Sunitinib Accord

Tell 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 may affect the levels of Sunitinib Accord in your body. You should tell your doctor if you are taking medicines that contain 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 diseases (such as allergic/respiratory disorders or skin diseases)
• phenytoin, carbamazepine, phenobarbital - used to treat epilepsy and other neurological diseases
• herbal remedies 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 taking Sunitinib Accord.

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.

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

If you are breast-feeding, tell your doctor. You should not breast-feed while taking Sunitinib Accord.

Driving and using machines

If you experience dizziness or unusual tiredness, be careful when driving or using machines.

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 for administration of this medicine given by your doctor. If you are unsure, ask your doctor again.

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

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

Your doctor will tell you the dose you need to take and when to stop treatment with Sunitinib Accord.

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, talk to your doctor immediately. You may need medical attention.

If you forget to take Sunitinib Accord

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

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

Heart problems. Consult your doctor if you feel very tired, are short of breath, or have swollen feet and ankles. They 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 breathing difficulties, or cough up blood. They 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 the frequency or absence of urination, as they may be symptoms of kidney failure.

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

Tumor destruction causing a hole in the intestine. Consult your doctor if you have severe abdominal pain, fever, nausea, vomiting, blood in your stool, or changes in your bowel movements.

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 fluids under the skin and around the eye, severe allergic rash.
• Mouth pain/irritation, mouth ulcers/inflammation/dryness, taste disorders, stomach upset, nausea, vomiting, diarrhea, constipation, abdominal pain/swelling, loss/decreased appetite.
• Decreased activity of the thyroid gland (hypothyroidism).
• Dizziness.
• Headache.
• Nosebleeds.
• Back pain, joint pain.
• Pain in arms and legs.
• Yellowing/discoloration of the skin, excessive skin pigmentation, hair color change, rash on the palms of the hands and soles of the feet, rash, dry skin.
• Cough.
• Fever.
• Difficulty sleeping.

Common: may affect up to 1 in 10 people

• Blood clots in blood vessels.
• Lack of blood flow to the heart muscle due to obstruction or constriction of the coronary arteries.
• Chest pain.
• Decrease in the 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 can cause tissue damage, organ failure, and death.
• Decreased blood sugar level (see section 2).
• Loss of protein in the urine that can cause swelling.
• Pseudogripal syndrome.
• Abnormal blood test results, including pancreatic and liver enzymes.
• High level of uric acid in the blood.
• Hemorrhoids, rectal pain, gum bleeding, difficulty swallowing, or inability to swallow.
• Burning sensation or pain in the tongue, inflammation of the digestive tract lining, excess gas in the stomach or intestine.
• Weight loss.
• Musculoskeletal pain (pain in muscles and bones), weakness, muscle fatigue, muscle pain, muscle spasms.
• Nasal dryness, nasal congestion.
• Excessive tear production.
• Abnormal sensation in the skin, itching, scaly and inflamed skin, blisters, acne, nail color change, hair loss.
• Abnormal sensation in the limbs.
• 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 life-threatening soft tissue infection, including 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.
• Abdominal pain caused by pancreas inflammation.
• Tumor destruction causing a hole in the intestine (perforation).
• Inflammation (swelling and redness) of the gallbladder, with or without gallstones.
• Abnormal tube-like structure, as if it were a conduit from a normal body cavity to another body cavity or to the skin.
• Pain in the mouth, teeth, and/or jaw, swelling or ulcers inside the mouth, numbness or a feeling of heaviness in the jaw, or a feeling that a tooth is loose. All of these can be signs and symptoms of jawbone 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 level of an enzyme (creatine phosphokinase) in the blood.
• Excessive reaction to an allergen, including allergy to pollen, skin rash, itching, hives, swelling of body parts, and difficulty breathing.
• Inflammation of the colon (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 encompasses a series of metabolic complications that can occur during cancer treatment. These complications are caused by products released by dying cancer cells and can include nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, darkening of the urine, and fatigue, associated with abnormal laboratory test results (high levels of potassium, uric acid, and phosphorus, and low levels of calcium in the blood) that can lead to changes in kidney function and acute kidney failure.
• Abnormal muscle breakdown that can lead to kidney problems (rhabdomyolysis).
• Abnormal changes in the brain that can cause a range of symptoms, including headache, confusion, seizures, and loss of vision (reversible posterior leukoencephalopathy syndrome).
• Painful skin ulceration (pyoderma gangrenosum).
• Liver inflammation (hepatitis).
• Thyroid gland inflammation.
• Damaged small blood vessels known as thrombotic microangiopathy (TMA).

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

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

Reporting of Adverse Effects

If you experience any adverse effect, consult 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 expiration date stated on the packaging, bottle, and blister after CAD or EXP. The expiration date is the last day of the month indicated.
• This medicine does not require special storage conditions.
• Do not use this medicine if you notice that the packaging is damaged or shows signs of having been opened.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Sunitinib Accord

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

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

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

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

Appearance of the Product and Package Contents

Sunitinib Accord 12.5mg hard capsules

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

Sunitinib Accord 25mg hard capsules

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

Sunitinib Accord 37.5mg hard capsules

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

Sunitinib Accord 50mg hard capsules

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

Not all 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

Date of the Last Revision of this Leaflet:{MM/AAAA}.

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