Sunitinib Silver 12.5 mg hard capsules EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Sunitinib Silver 12.5 mg hard capsules EFG

Sunitinib Silver 25 mg hard capsules EFG

Sunitinib Silver 50 mg hard capsules EFG

Read the entire leaflet carefully before you start taking this medicine, as 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 or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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

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

Sunitinib Silver contains the active substance sunitinib, which is a protein kinase inhibitor. It is used for the treatment of cancer and works by blocking the activity of a specific group of proteins involved in the growth and proliferation of cancer cells.

Sunitinib Silver 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 already 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 hormone-secreting cells in the pancreas) that have progressed or cannot be surgically removed.

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

2. What you need to know before starting to take Sunitinib Silver

Do not take Sunitinib Silver:

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

Warnings and precautions

Talk to your doctor before starting to take Sunitinib Silver:

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

• If you have or have had blood disorders, bleeding problems, or bruising. Treatment with Sunitinib Silver 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, medicines that thin the blood to prevent clots, there may be an increased risk of bleeding. If you experience any bleeding during treatment with Sunitinib Silver, consult your doctor.

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

• If you have abnormal changes in your heart rhythm. Sunitinib Silver may cause irregular heart rhythms. Your doctor may perform electrocardiograms (ECGs) to assess these issues during treatment with Sunitinib Silver. Contact your doctor if you feel dizzy, faint, or experience abnormal heartbeats while being treated with Sunitinib Silver.

• If you have recently had 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, 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 Silver.

• If you have or have had an aneurysm (a bulging 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 smallest blood vessels, known as Thrombotic Microangiopathy (TMA). Contact your doctor if you experience fever, fatigue, bruising, bleeding, swelling, confusion, vision loss, or seizures.

• If you have thyroid gland problems. Sunitinib Silver may cause thyroid-related issues. Contact your doctor if you feel unusually tired, feel colder than usual, or your voice becomes deeper while taking Sunitinib Silver. Thyroid function should be monitored before starting treatment with Sunitinib Silver and periodically during treatment. If your thyroid gland does not produce enough thyroid hormone, you may be treated with thyroid hormone replacement therapy.

• If you have or have had pancreatic or gallbladder disorders. Contact your doctor if you develop any of the following signs and 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 and symptoms of liver problems during treatment with Sunitinib Silver: 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 Silver, 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 Silver may affect wound healing. If you are scheduled for surgery, you will usually stop taking Sunitinib Silver. Your doctor will decide when to restart treatment.

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

• if you have or have had 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, inform your doctor and dentist immediately.

• if you need invasive dental treatment or dental surgery, inform your dentist that you are being treated with Sunitinib Silver, especially if you are also being treated or have been treated with intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone complications that may have been administered for another medical condition.

• 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 life-threatening). 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 after stopping sunitinib. Serious skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been reported with the use of sunitinib. These rashes initially appear as red, target-like spots or circular lesions, often with central blisters, typically on the trunk. The rash may progress to widespread blistering or skin peeling and can be life-threatening. Contact your doctor immediately if you develop a skin rash or the skin symptoms described.

• 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 the dose of antidiabetic medication needs adjustment, minimizing 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, or loss of consciousness).

Children and adolescents

The use of Sunitinib Silver is not recommended in individuals under 18 years of age.

Other medicines and Sunitinib Silver

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 Silver 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 Silver with food and drink

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

Pregnancy and breastfeeding

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

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

If you are breastfeeding, inform your doctor. You must not breastfeed during treatment with Sunitinib Silver.

Driving and using machines

If you experience dizziness or unusual tiredness, take special care when driving or operating machinery.

Sunitinib Silver contains Sodium

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

3. How to take Sunitinib Silver

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

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

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

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

Sunitinib Silver may be taken with or without food.

If you take more Sunitinib Silver than you should

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

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

If you forget to take Sunitinib Silver

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

4. Possible adverse effects

Like all medicines, this medicine may 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 What you need to know before starting to take Sunitinib Silver):

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

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

Bleeding. Consult your doctor if you experience any of these symptoms or have a serious bleeding problem during treatment with Sunitinib Silver: painful or swollen stomach (abdomen), vomiting blood, black and tarry stools, blood in urine, headache, changes 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 Silver may include:

Very common: may affect more than 1 in 10 people

• Reduction 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.
• Tissue swelling due to fluid accumulation under the skin and around the eye, severe allergic rash.
• Mouth pain/irritation, mouth sores/inflammation/dryness, 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.
• Yellow skin/skin color changes, excessive skin pigmentation, hair color changes, skin rash on palms of hands and soles of feet, rash, dry skin.
• Cough.
• Fever.
• Difficulty sleeping.

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 levels (see section 2).
• Protein loss in urine which may cause swelling.
• Pseudoflu-like syndrome.
• Abnormal blood test results, including pancreatic and liver enzymes.
• High levels of uric acid in blood.
• Haemorrhoids, rectal pain, gum bleeding, 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), muscle weakness, muscle fatigue, muscle pain, muscle spasms.
• Dry nose, nasal congestion.
• Excessive tear production.
• Abnormal skin sensations, itching, scaly and inflamed skin, blisters, acne, nail color changes, hair loss.
• Abnormal sensations in the limbs.
• Abnormally decreased/increased sensitivity, especially to touch.
• Stomach burning (heartburn).
• Dehydration.
• Hot flushes.
• Abnormal urine coloration.
• 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 heart's 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 jaw bone damage (osteonecrosis), see section 2.
• Overproduction of thyroid hormones increasing the body's resting energy expenditure.
• Wound healing problems after surgery.
• Elevated blood levels of a muscle enzyme (creatine phosphokinase).
• Severe allergic reaction, including pollen allergy, skin rash, skin itching, hives, swelling of body parts, and breathing difficulties.
• 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 group 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, cloudy urine, and fatigue, associated with abnormal laboratory test 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 leading to kidney problems (rhabdomyolysis).
• Abnormal changes in the brain that may cause a range of symptoms including headache, confusion, seizures, and vision loss (reversible posterior leukoencephalopathy 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).

Frequency not known (cannot be estimated from available data)

• Enlargement and weakening of a blood vessel wall or tear in 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 or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Sunitinib Silver

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the outer packaging, bottle, and blister after 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 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 empty containers and unused medicines at the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the pack and other information Composition of Sunitinib Silver

Sunitinib Silver 12.5 mg hard capsules

The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 12.5 mg of sunitinib. The other components are:

• Capsule contents: mannitol, povidone (K-25), sodium croscarmellose, and magnesium stearate.
• Capsule coating: gelatin, iron oxide red (E172), and titanium dioxide (E171).

Sunitinib Silver 25 mg hard capsules

The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 25 mg. The other components are:

• Capsule contents: mannitol, povidone (K-25), sodium croscarmellose, and magnesium stearate.
• Capsule coating: gelatin, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172), and iron oxide black (E172).

Sunitinib Silver 50 mg hard capsules

The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 50 mg. The other components are:

• Capsule contents: mannitol, povidone (K-25), sodium croscarmellose, and magnesium stearate.
• Capsule coating: gelatin, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172), and iron oxide black (E172).

Presentation of the product and contents of the pack

Sunitinib 12.5 mg is supplied as hard gelatin capsules with an orange cap and an orange body, containing yellow to orange granules.

Sunitinib 25 mg is supplied as hard gelatin capsules with a caramel-colored cap and an orange body, containing yellow to orange granules.

Sunitinib 50 mg is supplied as hard gelatin capsules with a caramel-colored cap and a caramel-colored body, containing yellow to orange granules.

Sunitinib Silver is available in white bottles containing 30 capsules and in blister packs of 28 or 30 capsules.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

SILVER PHARMA S.L.

Avda. Camino de lo Cortao 16

28703 San Sebastian de los Reyes, Madrid

Spain

Manufacturer

Combino Pharm (Malta) Ltd.

HF 60, Hal Far Industrial Estate

Hal Far, BBG 3000

Malta

Date of the latest revision of this package leaflet: May 2024

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