Prospect: 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 this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed to you alone, 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 adverse effects, consult your doctor, even if they are not listed in this prospect. See section 4.

Sunitinib Silver 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 Silver 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 Silver works or why this medication has been prescribed for you, consult your doctor.

Do not take Sunitinib Silver:

• 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 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 medications that reduce blood pressure.

• If you have or have had blood disorders, bleeding problems or bruising. Treatment with Sunitinib Silver may lead to a high risk of bleeding or produce changes in the number of certain blood cells, which can 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 Silver, consult your doctor.

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

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

• 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 on treatment with Sunitinib Silver.

• 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 suffer or have suffered damage to the smaller blood vessels known as Microangiopathy (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 Silver 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 Silver. Before starting treatment with Sunitinib Silver and periodically while taking it, your thyroid function should be monitored. If your thyroid gland does not secrete enough thyroid hormone, you may be treated with thyroid hormone replacement.

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

• 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, yellow eyes or skin, dark urine, and pain or discomfort in the upper right abdominal area. Your doctor should perform blood tests to monitor liver function before and during treatment with Sunitinib Silver, 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 Silver may affect wound healing. If you are to undergo surgery, you will usually stop taking Sunitinib Silver. Your doctor will decide when to start taking Sunitinib Silver again.

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

• if you have or have had mouth pain, tooth pain, or gum pain, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw, or if you have a loose tooth, inform your doctor and dentist immediately.

• if you need to have invasive dental treatment or dental surgery, inform your dentist that you are taking Sunitinib Silver, particularly if you are also taking or have been treated with bisphosphonates intravenously. Bisphosphonates are medications 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 medication, you may develop "pyoderma gangrenosum" (painful skin ulceration) or "necrotizing fasciitis" (infection of the skin/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 discharge of pus or blood. 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, inform your doctor as soon as possible.

• If you have diabetes.Your blood glucose levels should be checked regularly to assess whether your diabetes 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 Silver is not recommended for use in patients under 18 years of age.

Other medications and Sunitinib Silver

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

Some medications may affect the levels of Sunitinib Silver in your body. You should inform your doctor if you are taking medications 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 remedies containing St. John's Wort or hypericum (Hypericum perforatum) – used to treat depression and anxiety

Taking Sunitinib Silver with food and drinks

You should avoid taking grapefruit juice while on treatment with Sunitinib Silver.

Pregnancy and breastfeeding

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

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

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

Driving and operating machinery

If you experience dizziness or unusual fatigue, be extra careful when driving or operating machinery.

Sunitinib Silver contains Sodium

This medication contains less than 1 mmol of sodium (23 mg) per capsule; 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 suitable dose you need to take, as well as whether you need to suspend treatment with Sunitinib Silver and when.

Sunitinib Silver can 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, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91.562.04.20 indicating the medication and the amount ingested.

If you forgot to take Sunitinib Silver

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 shouldcontactyour doctor immediatelyif you experience any of the following serious side effects (see alsoWhat you need to know before starting to take Sunitinib Silver):

Heart problems. Consult your doctor if you are 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 breathing difficulties, 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 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 Silver: stomach (abdomen) pain or swelling, vomit blood, have black and sticky stools, urinate blood, have a headache or any change in your mental state, cough up blood or have bloody sputum from the lungs or respiratory tract.

Tumor destruction causing a perforation in the intestine. 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 Silver 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 tiredness, loss of strength.
• Swelling of tissues caused by fluid under the skin and around the eye, severe allergic rash.
• Mouth pain/irritation, mouth ulcers/inflammation/dryness, taste disturbances, stomach problems, nausea, vomiting, diarrhea, constipation, abdominal pain/hardness, loss/reduced appetite.
• Decreased activity of the thyroid gland (hypothyroidism).
• Dizziness.
• Headache.
• Nosebleed.
• Back pain, joint pain.
• Pain in arms and legs.
• Yellow skin/color changes in skin, excessive skin pigmentation, hair color change, skin rash on palms of hands and soles of feet, rash, skin dryness.
• 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 constriction of coronary arteries.
• Chest pain.
• Decreased amount of blood pumped by the heart.
• 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.
• Alteration of blood tests including pancreatic and liver enzymes.
• Elevated blood uric acid levels.
• 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), muscle weakness, muscle fatigue, muscle pain, muscle spasms.
• Nasal dryness, nasal congestion.
• Excessive tear production.
• Abnormal skin sensation, itching, scaly and inflamed skin, blisters, acne, nail color change, hair loss.
• Abnormal sensation in extremities.
• Abnormally decreased/increased sensitivity, especially to touch.
• Stomach burning.
• Dehydration.
• Hot flushes.
• 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 insufficiency.
• Abdominal pain caused by pancreatitis inflammation.
• Tumor destruction causing a perforation in the intestine.
• Bile duct inflammation, associated or not with gallstones.
• Abnormal tube formation as if it were a conduit from a normal body cavity to another body cavity or to the skin.
• Mouth pain, tooth pain, and/or jaw pain, swelling or ulcers inside the mouth, numbness or a feeling of heaviness in the jaw, or the feeling that a tooth is loose. All of these may be signs and symptoms of jaw bone damage (osteonecrosis), see section 2.
• Excessive production of thyroid hormones that increase the amount of energy the body consumes at rest.
• Problems with wound healing after surgery.
• Elevated blood levels of a muscle enzyme (creatine phosphokinase).
• 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, cloudy 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 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 range 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 tearing of the blood vessel wall (aneurysms and arterial dissections).
• Low energy, confusion, drowsiness, loss of consciousness/coma: these symptoms may be signs of brain toxicity caused by elevated ammonia levels in the blood (hyperammonemic encephalopathy).

• Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es.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 outer packaging and the bottle and blister pack after CAD. 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 container is damaged or shows signs of having been opened.

Medications should not be disposed of through drains or in the trash. Dispose of the containers and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. By doing so, you will help protect the environment..

Sunitinib Silver12.5 mg hard capsules

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

-Capule content: mannitol, povidone (K-25), sodium croscarmellose, and magnesium stearate.

-Capule coating: gelatin, iron oxide red (E172), and titanium dioxide (E171).

Sunitinib Silver25 mg hard capsules

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

-Capule content: mannitol, povidone (K-25), sodium croscarmellose, and magnesium stearate.

-Capule coating: gelatin, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172), and iron oxide black (E172).

Sunitinib50 mg hard capsules

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

-Capule content: mannitol, povidone (K-25), sodium croscarmellose, and magnesium stearate.

-Capule coating: gelatin, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172), and iron oxide black (E172).

Appearance of the product and contents of the package

Sunitinb 12.5 mg is presented in hard gelatin capsules with an orange-colored cap and a yellow-orange-colored body, containing yellow-orange-colored granules.

Sunitinb 25 mg is presented in hard gelatin capsules with a caramel-colored cap and a yellow-orange-colored body, containing yellow-orange-colored granules.

Sunitinb 50 mg is presented in hard gelatin capsules with a caramel-colored cap and a caramel-colored body, containing yellow-orange-colored granules.

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

Only some package sizes may be commercially available.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

SILVER PHARMA S.L.

Avda. Camino de lo Cortao 16

28703 San Sebastian de los Reyes, Madrid

Spain

Responsible manufacturer

Combino Pharm (Malta) Ltd.

HF 60, Hal Far Industrial Estate

Hal Far, BBG 3000

Malta

Last review date of this leaflet:May 2024

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