SUNITINIB TEVA 12.5 mg HARD CAPSULES

Introduction

Package Leaflet:information for the user

Sunitinib Teva 12.5 mg hard capsules EFG

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 or pharmacist.

• This medicine has been prescribed for you only, and you should not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Sunitinib Teva is and what it is used for
2. What you need to know before you take Sunitinib Teva
3. How to take Sunitinib Teva
4. Possible side effects

5 Storage of Sunitinib Teva

1. Contents of the pack and other information

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

Sunitinib Teva 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 Teva 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 Teva works or why this medicine has been prescribed for you, ask your doctor.

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

Do not take Sunitinib Teva:

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

Warnings and precautions

Talk to your doctor before taking Sunitinib Teva:

• If you have high blood pressure. Sunitinib Teva may increase your blood pressure. Your doctor may check your blood pressure during treatment with Sunitinib Teva and may treat you with medicines that lower blood pressure if necessary.

• If you have or have had bleeding problems or blood clotting problems. Treatment with Sunitinib Teva 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 blood clots, there may be a higher risk of bleeding. If you experience any bleeding during treatment with Sunitinib Teva, talk to your doctor.

• If you have heart problems. Sunitinib Teva may cause heart problems. Talk to your doctor if you feel very tired, short of breath, or if your feet and ankles are swollen.

• If you have changes in heart rhythm. Sunitinib Teva may cause changes in heart rhythm. Your doctor may perform electrocardiograms to evaluate these problems during treatment with Sunitinib Teva. Talk to your doctor if you feel dizzy, faint, or have irregular heartbeats during treatment with Sunitinib Teva.

• 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 immediatelyif you have 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 Teva.

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

• If you have been diagnosed with an enlarged or "bulging" aorta, known as an aortic aneurysm.

• If you have previously experienced a tear in the wall of the aorta, known as an aortic dissection.

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

• If you have thyroid problems. Sunitinib Teva may cause thyroid problems. Contact your doctor if you feel more tired than usual, feel colder than others, or if your voice becomes hoarse while taking Sunitinib Teva. Before and periodically during treatment with Sunitinib Teva, your thyroid function should be checked. 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 problems. Contact 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. Contact your doctor if you develop any of the following signs and symptoms of liver problems during treatment with Sunitinib Teva: itching, yellow eyes or skin, dark urine, and pain or discomfort in the upper right stomach area. Your doctor should perform blood tests to monitor liver function before and during treatment with Sunitinib Teva, 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 Teva may affect wound healing. If you are going to have an operation, you will usually stop taking Sunitinib Teva. Your doctor will decide when to start Sunitinib Teva again.

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

1. - 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.
2. - if you need to have invasive dental treatment or dental surgery, tell your dentist that you are taking Sunitinib Teva, especially if you are also being treated with intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone complications that may have been given for 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. Contact your doctor immediately if you have 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 rash (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) associated with the use of sunitinib, which initially had the appearance of target-like spots or circular patches, often accompanied by central blisters on the trunk. This rash may progress to widespread blisters or peeling of the skin and may be life-threatening. Contact your doctor immediatelyif you develop a skin rash or the skin symptoms mentioned.

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

• If you have diabetes. Blood glucose levels should be regularly checked in diabetic patients to assess whether the dose of the anti-diabetic medication needs to be adjusted to minimize the risk of low blood sugar. 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 Teva is not recommended for use in children and adolescents under 18 years of age.

Other medicines and Sunitinib Teva

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 Teva 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 HIV
• 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 disorders
• herbal medicines containing St. John's Wort (Hypericum perforatum) - used to treat depression and anxiety

Taking Sunitinib Teva with food and drinks

You should avoid drinking grapefruit juice while taking Sunitinib Teva.

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 Teva.

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

Driving and using machines

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

Sunitinib Teva contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per capsule; this is essentially "sodium-free".

3. How to take Sunitinib Teva

Follow exactly the administration instructions 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) without medication in 6-week cycles.
• pNET: the usual dose is 37.5 mg once a day without a break.

Your doctor will tell you the dose you need to take and when you may need to stop taking Sunitinib Teva.

Sunitinib Teva can be taken with or without food.

If you take more Sunitinib Teva than you should

If you have accidentally taken too many capsules, talk to your doctor immediately. You may need medical attention.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91.562.04.20, indicating the medicine and the amount taken.

If you forget to take Sunitinib Teva

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 immediatelyif you experience any of these serious adverse effects (see also What you need to know before taking Sunitinib Teva):

Heart problems. Consult your doctor if you feel very tired, are short of breath, or have swollen feet and ankles. These may be symptoms of heart problems, including 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. 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 a change 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 a severe bleeding problem during treatment with Sunitinib Teva: painful or swollen stomach (abdomen), vomiting blood, black and tarry stools, blood in the urine, headache, or changes in mental status, 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 the stool, or changes in bowel habits.

Other adverse effects with Sunitinib Teva may include:

Very common: may affect more than 1 in 10 people

• Reduced number of platelets, red blood cells, and/or white blood cells (e.g., neutrophils).
• Difficulty breathing.
• High blood pressure.
• Extreme fatigue, loss of strength.
• 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.
• Yellow skin/color changes, excessive skin pigmentation, hair color changes, 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.
• Decreased 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.
• Low blood sugar levels (see section 2). Loss of protein in the urine, which can cause swelling.
• Pseudogrip syndrome.
• Abnormal blood test results, including pancreatic and liver enzymes.
• High levels 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), muscle 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 changes, 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 anal-genital area (see section 2).
• Stroke
• Myocardial infarction (heart attack) caused by interruption or reduction of blood flow to the heart.
• Changes in heart rhythm 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 from a normal body cavity to another cavity or skin.
• Mouth pain, tooth and/or jaw pain, swelling or ulcers inside the mouth, numbness or a feeling of heaviness in the jaw, or a feeling that a tooth is loose. These may 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 levels of a muscle enzyme (creatine phosphokinase) in the blood.
• Excessive reaction to an allergen, including pollen allergy, 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 may include nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, clouding of 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 brain changes that can cause a range of symptoms, including headache, confusion, seizures, and vision loss (posterior reversible leukoencephalopathy syndrome).
• Painful skin ulcers (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)

• Enlargement and weakening of a blood vessel wall or tear in the 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 (hyperammonemic encephalopathy).

Reporting adverse effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the Spanish Medicines and Health Products Agency's pharmacovigilance system: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Sunitinib Teva

• Keepthis medicineout of sight and reach of children.
• Do not use this medicine after the expiration date stated on the outer packaging and blister pack after CAD or EXP. The expiration date is the last day of the month indicated.
• Do not store above 30°C. Store in the original package to protect from moisture.
• 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. Dispose of packaging and unused medicines at the pharmacy's SIGRE collection point. If in doubt, ask your pharmacist how to dispose of packaging and unused medicines. This will help protect the environment.

6. Package contents and additional information

Composition of Sunitinib Teva

Sunitinib Teva 12.5 mg hard capsules

The active ingredient is sunitinib. Each capsule contains 12.5 mg of sunitinib.

The other ingredients are:

• Capsule content: mannitol, povidone K-25, sodium croscarmellose, magnesium stearate.
• Capsule shell: gelatin, titanium dioxide (E171), red iron oxide (E172), and yellow iron oxide (E172)
• Printing ink: shellac, black iron oxide (E172), propylene glycol, concentrated ammonia solution, and potassium hydroxide.

Appearance and package contents of the product

Sunitinib Teva 12.5 mg hard capsules

Hard gelatin capsules with an opaque orange cap and an opaque orange body, with "12.5" printed in black ink on the cap. Each size 4 capsule (approximately 14.2 mm in length when closed) contains an orange granular powder.

Sunitinib Teva is available in white HDPE bottles of 30 capsules, blister packs of 28 and 30 capsules, and single-dose blisters containing 28x1 and 30x1 capsules.

Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Teva B.V.

Swensweg 5, 2031 GA Haarlem

Netherlands

Manufacturer

Teva Operations Poland Sp. z.o.o

ul. Mogilska 80

31-546 Kraków

Poland

or

Merckle GmbH

Ludwig-Merckle-Strasse 3, Blaubeuren

89143 Baden-Wuerttemberg

Germany

or

PLIVA Hrvatska d.o.o. (PLIVA Croatia Ltd.)

Prilaz baruna Filipovica 25

10000 Zagreb

Croatia

or

Actavis International Ltd.

4 Sqaq tal-Gidi off Valletta Road,

Luqa LQA 6000,

Malta

or

Balkanpharma-Dupnitsa AD

3 Samokovsko Shosse Str.,

Dupnitsa, 2600

Bulgaria

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Teva Pharma, S.L.U.

C/ Anabel Segura 11, Edificio Albatros B, 1ª planta

28108 Alcobendas (Madrid)

Spain

Date of the last revision of this leaflet:November 2019

Detailed information about this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)