Subinit

Package Leaflet: Information for the User

Subinit, 12.5 mg, hard capsules

Subinit, 25 mg, hard capsules

Subinit, 50 mg, hard capsules

Sunitinib

Read all of this leaflet carefully before 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. 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

• 1. What Subinit is and what it is used for
• 2. Before you take Subinit
• 3. How to take Subinit
• 4. Possible side effects
• 5. How to store Subinit
• 6. Contents of the pack and other information

1. What Subinit is and what it is used for

Subinit contains the active substance sunitinib, which is a protein kinase inhibitor. Subinit is used to treat cancer. It works by inhibiting the activity of a specific group of proteins, known to be involved in the growth and spread of cancer cells. Subinit is used to treat the following types of cancer in adults:

• Gastrointestinal stromal tumour (GIST), a type of stomach and intestine cancer, when imatinib (another anti-cancer medicine) has stopped working or the patient cannot take it;
• Metastatic renal cell carcinoma (MRCC), a type of kidney cancer that has spread to other parts of the body;
• Pancreatic neuroendocrine tumours (PNET), tumours that arise from hormone-producing cells in the pancreas, which are in an advanced stage and cannot be surgically removed.

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

2. Before you take Subinit

When not to take Subinit

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

Warnings and precautions

Before taking Subinit, discuss with your doctor:

• If you have high blood pressure.Subinit may increase your blood pressure. Your doctor may check your blood pressure during treatment with Subinit, and you may need to take medicines to lower your blood pressure.
• If you have or have had bleeding or blood clotting problems.Treatment with Subinit may increase the risk of bleeding or changes in the number of certain blood cells, which can cause anaemia or affect the blood's ability to clot. If you are taking warfarin or acenocoumarol, blood-thinning medicines used to prevent blood clots, you may be at increased risk of bleeding. Tell your doctor about any bleeding during treatment with Subinit.
• If you have heart problems.Subinit may cause heart problems. Tell your doctor if you experience extreme tiredness, shortness of breath, or swelling of your feet or ankles.
• If you have irregular heartbeats.Subinit may cause irregular heartbeats. During treatment with Subinit, your doctor may perform an electrocardiogram to check for these irregularities. Tell your doctor if you experience dizziness, fainting, or irregular heartbeat while taking Subinit.
• If you have recently had blood clots in your veins and/or arteries (a type of blood vessel), including stroke, heart attack, blockage, or blood clot.Contact your doctor immediately if you experience symptoms such as chest pain or tightness, arm, back, neck, or jaw pain, shortness of breath, numbness or weakness on one side of the body, difficulty speaking, headache, or dizziness.
• If you have or have had an aneurysm (a bulge or weakening of the wall of a blood vessel) or a tear in the wall of a blood vessel.
• If you have or have had a condition called thrombotic microangiopathy (a condition where small blood vessels become blocked).Tell your doctor if you experience fever, fatigue, weakness, bruising, bleeding, swelling, confusion, loss of vision, or seizures.
• If you have thyroid problems.Subinit may cause thyroid problems. Tell your doctor if you feel extremely tired, feel colder than others, or experience a deepened voice while taking Subinit. Your doctor should check your thyroid function before starting Subinit and regularly during treatment. If your thyroid gland does not produce enough thyroid hormone, you may need to take replacement thyroid hormone.
• If you have or have had pancreas or gallbladder problems.Tell your doctor if you experience any of the following symptoms: stomach pain (upper abdomen), nausea, vomiting, and fever. These may be symptoms of pancreatitis or gallbladder inflammation.
• If you have or have had liver problems.Inform your doctor if you experience any of the following symptoms of liver problems while taking Subinit: itching, yellowing of the eyes or skin, dark urine, and pain or discomfort in the right upper abdomen. Your doctor should perform blood tests to check your liver function before starting Subinit, during treatment, and if there are any signs of liver problems.

and will monitor your kidney function.

• If you have or have had kidney problems.
• If you are going to have surgery or have recently had surgery.Subinit may affect wound healing. The medicine is usually stopped in patients before surgery. Your doctor will decide when to restart Subinit.
• A dental examination is recommended before starting treatment with Subinit.
• if you experience mouth pain, toothache, jaw pain or swelling, mouth ulceration, numbness or a feeling of heaviness in the jaw, or tooth mobility, tell your doctor or dentist immediately.
• if you need invasive dental work or surgery, you should inform your dentist that you are taking Subinit, especially if you are also taking or have taken intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone disease that may be taken for another condition.
• If you have or have had skin and subcutaneous tissue disorders.While taking this medicine, you may experience a condition called pyoderma gangrenosum (painful skin ulceration) or necrotizing fasciitis (a rapidly spreading infection of the skin and/or soft tissues that can be life-threatening). Contact your doctor immediately if you experience symptoms of infection around a skin lesion, including fever, pain, redness, swelling, or discharge of pus or blood. These conditions usually resolve after stopping Subinit. While taking this medicine, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed, which initially appear as reddened targets or circular patches, often with central blisters. The rash may progress to widespread blisters or peeling of the skin and can be life-threatening. If you experience a rash or the above skin symptoms, contact your doctor immediately.
• If you have or have had seizures.Inform your doctor as soon as possible if you experience high blood pressure, headache, loss of vision.
• If you have diabetes.In patients with diabetes, blood sugar levels should be regularly checked to assess whether the dose of anti-diabetic medicine needs to be adjusted to minimize the risk of low blood sugar. Inform your doctor as soon as possible if you experience symptoms of low blood sugar (tiredness, palpitations, sweating, hunger, and loss of consciousness).

Children and adolescents

Subinit is not recommended for patients under 18 years of age.

Subinit and other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, including those obtained without a prescription and those you plan to take. Some medicines may affect the levels of Subinit in your body. Inform your doctor if you are taking medicines containing the following active substances:

• ketokonazole, itraconazole - used to treat fungal infections,
• erythromycin, clarithromycin, rifampicin - used to treat infections,
• ritonavir - used to treat HIV infections,
• dexamethasone - a corticosteroid used in various diseases (such as allergic disorders and/or respiratory disorders or skin diseases),
• phenytoin, carbamazepine, phenobarbital - used to treat epilepsy and other neurological conditions,
• herbal products containing St. John's Wort (Hypericum perforatum) - used to treat depression and anxiety.

Taking Subinit with food and drink

Do not drink grapefruit juice while taking Subinit.

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. Women who may become pregnant should use effective contraception during treatment with Subinit. Breast-feeding should be stopped during treatment with Subinit. Do not breast-feed while taking Subinit.

Driving and using machines

If you experience dizziness or extreme tiredness, be careful when driving or operating machinery.

Subinit contains sodium

Subinit contains less than 1 mmol sodium (23 mg) per capsule, which is essentially 'sodium-free'.

3. How to take Subinit

Always take this medicine exactly as your doctor has told you. If you are not sure, check with your doctor. Your doctor will prescribe the dose that is right for you, depending on the type of cancer you have. For patients being treated for:

• GIST or MRCC, the usual dose is 50 mg taken once daily for 28 days (4 weeks), followed by a 14-day (2-week) break (without Subinit), in 6-week cycles of treatment.
• PNET, the usual dose is 37.5 mg taken once daily continuously.

Your doctor will determine the correct dose for you and when to stop taking Subinit. Subinit can be taken with or without food.

If you take more Subinit than you should

If you have taken too many capsules, contact your doctor immediately. Medical attention may be necessary.

If you forget to take Subinit

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Contact your doctor immediately if you experience any of the following side effects (see also section 2):

Heart problems.Tell your doctor if you feel extremely tired, have shortness of breath, or swelling of your feet and ankles. These may be symptoms of heart problems, including heart failure and heart muscle problems (cardiomyopathy).

Lung or breathing problems.Tell your doctor if you experience coughing, chest pain, sudden shortness of breath, or coughing up blood. These may be symptoms of a condition called pulmonary embolism, which occurs when blood clots move to the lungs.

Kidney problems.Tell your doctor if you experience changes in urination frequency or inability to urinate, which may be a sign of kidney failure.

Bleeding.Tell your doctor if you experience any of the following symptoms or severe bleeding during treatment with Subinit: stomach pain and swelling (abdomen); vomiting blood; black and tarry stools; blood in urine; headache or changes in consciousness; coughing up blood or bloody sputum from the lungs or airways.

Tumour breakdown leading to bowel perforation.Tell your doctor if you experience severe abdominal pain, fever, nausea, vomiting, blood in stool, or changes in bowel movements.

Other side effects of Subinit may include:

Very common (may affect more than 1 in 10 people):

• Decreased number of platelets, red blood cells, and/or white blood cells (e.g., neutrophils).
• Shortness of breath.
• High blood pressure.
• Extreme tiredness, loss of strength.
• Swelling caused by fluid accumulation under the skin and around the eyes, allergic rash, deep.
• Pain and/or irritation in the mouth, painful ulcers and/or inflammation, and/or dryness of the mouth, taste disturbances, stomach upset, nausea, vomiting, diarrhea, constipation, abdominal pain and/or swelling, loss of and/or decreased appetite.
• Decreased thyroid activity (hypothyroidism).
• Dizziness.
• Headache.
• Nosebleeds.
• Back pain, joint pain.
• Pain in arms and legs.
• Yellowing of the skin and/or discoloration, excessive pigmentation of the skin, hair color changes, rash on palms and soles, rash, dry skin.
• Cough.
• Fever.
• Difficulty sleeping.

Common (may affect up to 1 in 10 people):

• Blood clots in blood vessels.
• Inadequate blood supply to the heart due to blockage or narrowing of the coronary arteries.
• Chest pain.
• Decreased amount of blood pumped by the heart.
• Fluid accumulation, including in the lungs.
• Infections.
• A complication after a severe infection (sepsis), which can lead to tissue damage, organ failure, and death.
• Low blood sugar levels (see section 2).
• Protein loss in urine, sometimes causing swelling.
• Pseudo-flu syndrome.
• Abnormal blood test results, including pancreatic and liver enzymes.
• High levels of uric acid in the blood.
• Hemorrhoids, anal pain, gum bleeding, difficulty swallowing or loss of swallowing ability.
• Burning sensation or pain in the tongue, inflammation of the mucous membrane of the digestive tract, excessive gas in the stomach or intestines.
• Weight loss.
• Musculoskeletal pain (muscle and bone pain), muscle weakness, muscle fatigue, muscle pain, muscle cramps.
• Dryness of the nasal mucosa, feeling of nasal congestion.
• Excessive tearing.
• Skin sensitivity disorders, itching, peeling and inflammation of the skin, blisters, acne, nail discoloration, hair loss.
• Skin sensation disorders.
• Sensitivity disorders related to increased or decreased sensitivity, especially to touch.
• Heartburn.
• Dehydration.
• Hot flashes.
• Abnormal urine color.
• Depression.
• Chills.

Uncommon (may affect up to 1 in 100 people):

• A life-threatening infection of the soft tissues, including the perianal and genital area (see section 2).
• Stroke.
• Heart attack caused by interruption or reduction of blood supply to the heart.
• Changes in the electrical or rhythm activity of the heart.
• Fluid accumulation around the heart (pericardial effusion).
• Liver failure.
• Stomach pain (abdomen) caused by pancreatitis.
• Tumour breakdown leading to bowel perforation (perforation).
• Inflammation (swelling or redness) of the gallbladder with or without gallstones.
• Formation of abnormal connections between one body cavity and another or with the skin.
• Mouth pain, toothache, jaw pain or swelling, mouth ulceration, numbness or a feeling of heaviness in the jaw, or tooth mobility. These may be symptoms of jawbone damage (necrosis), see section 2.
• Excessive production of thyroid hormones leading to increased resting metabolism.
• Abnormal wound healing after surgery.
• Increased activity of the muscle enzyme (creatine phosphokinase) in the blood.
• Excessive allergic reaction, including hay fever, skin rash, itching, hives, swelling of any part of the body, and difficulty breathing.
• Inflammation of the large intestine (colitis, ischemic colitis).

Rare (may affect up to 1 in 1000 people)

• Severe skin and/or mucous membrane reaction (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).
• Tumour lysis syndrome, a group of metabolic complications that can occur during cancer treatment. These complications are caused by the breakdown products of dying cancer cells and can include nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, and changes in laboratory test results (high levels of potassium, uric acid, and phosphorus, and low levels of calcium in the blood), which can lead to kidney damage and acute kidney failure.
• Abnormal muscle breakdown, which can cause kidney disease (rhabdomyolysis).
• Abnormal changes in the brain, which can cause a syndrome of symptoms including headache, disorientation, seizures, and loss of vision (reversible posterior leukoencephalopathy syndrome).
• Painful skin ulcers (pyoderma gangrenosum).
• Hepatitis.
• Thyroid inflammation.
• Damaged small blood vessels called thrombotic microangiopathy.

Frequency not known (frequency cannot be estimated from the available data)

• Enlargement and weakening of the wall of a blood vessel or rupture of the wall of a blood vessel (aneurysm and arterial dissection).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the contact details below. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Subinit

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date refers to the last day of that month.
• Store in a temperature below 30°C. Store in the original package to protect from light.
• Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Subinit contains

Subinit 12.5 mg hard capsules

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

• Capsule content: mannitol (E 421), croscarmellose sodium, povidone K-25, hypromellose 4 mPas, and magnesium stearate.
• Capsule shell - cap: erythrosine (E 127), titanium dioxide (E 171), indigo carmine (E 132), gelatin.
• Capsule shell - body: indigo carmine (E 132), erythrosine (E 127), titanium dioxide (E 171), gelatin.

Subinit 25 mg hard capsules

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

• Capsule content: mannitol (E 421), croscarmellose sodium, povidone K-25, hypromellose 4 mPas, and magnesium stearate.
• Capsule shell - cap: titanium dioxide (E 171), iron oxide yellow (E 172), gelatin.
• Capsule shell - body: indigo carmine (E 132), erythrosine (E 127), titanium dioxide (E 171), gelatin.

Subinit 50 mg hard capsules

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

• Capsule content: mannitol (E 421), croscarmellose sodium, povidone K-25, hypromellose 4 mPas, and magnesium stearate.
• Capsule shell - cap: titanium dioxide (E 171), iron oxide yellow (E 172), gelatin.
• Capsule shell - body: titanium dioxide (E 171), iron oxide yellow (E 172), gelatin.

What Subinit looks like and contents of the pack

Subinit 12.5 mg is available as hard, non-transparent, red and red gelatin capsules (size 4) containing yellow to orange granules. Subinit 25 mg is available as hard, non-transparent, yellow and red gelatin capsules (size 2) containing yellow to orange granules. Subinit 50 mg is available as hard, non-transparent, yellow and yellow gelatin capsules (size 1) containing yellow to orange granules. The medicine is available in PVC/Aclar (PCTFE)/PVC/Aluminium blisters. The carton contains 28 capsules.

Marketing Authorisation Holder

MT Pharma - Healthcare Sp. z o. o., ul. Józefa Piłsudskiego 25, 16-500 Sejny, Poland, tel.: +48 603 400 858

Manufacturer

Przedsiębiorstwo Farmaceutyczne LEK-AM sp. z o.o., ul. Ostrzykowizna 14A, 05-170 Zakroczym

Date of last revision of the leaflet: October 2023