Sunitinib bluefish

Package leaflet: Information for the patient

Sunitinib Bluefish, 12.5 mg, hard capsules
Sunitinib Bluefish, 25 mg, hard capsules
Sunitinib Bluefish, 50 mg, hard capsules
Sunitinibum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as 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 personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of the leaflet

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

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

Sunitinib Bluefish contains the active substance sunitinib, which is a protein kinase inhibitor.
Sunitinib Bluefish is used in the treatment of certain cancers. It inhibits the activity of a specific group
of proteins known to be involved in the growth and spread of cancer cells.
Sunitinib Bluefish is used to treat the following types of cancer in adults:

• Gastrointestinal stromal tumours (GIST), a type of stomach and intestinal cancer, when imatinib (another anticancer medicine) is no longer effective 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 arising from hormone-producing cells in the pancreas), which are progressing and cannot be surgically removed.

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

2. Important information before taking Sunitinib Bluefish

When not to take Sunitinib Bluefish

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

Warnings and precautions
Before starting treatment with Sunitinib Bluefish, discuss the following with your doctor:

• If high blood pressure is present. Sunitinib Bluefish may increase blood pressure. Your doctor may monitor your blood pressure during treatment with Sunitinib Bluefish, and you may be treated with antihypertensive medicines if necessary.
• If you have or have had blood disorders, bleeding, or bruising. Treatment with Sunitinib Bluefish may increase the risk of bleeding or cause changes in the number of certain blood cells, which may lead to anaemia or affect the blood’s ability to clot. If you are taking warfarin or acenocoumarol, anticoagulant medicines used to prevent blood clots, there may be an increased risk of bleeding. Inform your doctor about any bleeding episodes during treatment with Sunitinib Bluefish.
• If you have heart conditions. Sunitinib Bluefish may cause heart problems. Inform your doctor if you experience unusual fatigue, shortness of breath, or swelling in your feet or ankles.
• If you have heart rhythm disorders. Sunitinib Bluefish may cause irregular heart rhythms. During treatment with Sunitinib Bluefish, your doctor may perform an electrocardiogram (ECG) to monitor for such disturbances. Inform your doctor if you experience dizziness, fainting, or irregular heartbeat while taking Sunitinib Bluefish.
• If you have recently had blood clots in veins and/or arteries (types of blood vessels), including stroke, heart attack, pulmonary embolism, or thrombosis. Contact your doctor immediately if, during treatment with Sunitinib Bluefish, you experience symptoms such as chest pain or tightness, pain in the arms, back, neck, or jaw, 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 and weakening of the blood vessel wall) or a tear in the blood vessel wall.
• If you have or have had damage to the smallest blood vessels, known as thrombotic microangiopathy. Inform your doctor if you develop fever, fatigue, weakness, bruising, bleeding, swelling, confusion, vision loss, or seizures.
• If you have thyroid disorders. Sunitinib Bluefish may cause thyroid problems. Inform your doctor if you feel unusually tired, feel colder than others, or experience voice changes during treatment with Sunitinib Bluefish. Your doctor should check thyroid function before starting Sunitinib Bluefish and regularly during treatment. If your thyroid does not produce enough thyroid hormone, you may require thyroid hormone replacement therapy.
• If you have or have had pancreatic disorders or gallbladder problems. Inform your doctor if you experience any of the following symptoms: stomach pain (upper abdomen), nausea, vomiting, or fever. These may be signs of pancreatitis or gallbladder inflammation.
• If you have or have had liver disease. Inform your doctor if, during treatment with Sunitinib Bluefish, you develop any of the following signs of liver problems: itching, yellowing of the eyes or skin (jaundice), dark urine, or pain or discomfort in the upper right part of the abdomen. Your doctor should perform blood tests to monitor liver function before starting Sunitinib Bluefish, during treatment, and whenever clinically indicated.
• If you have or have had kidney disease. Your doctor will monitor kidney function.
• If you are scheduled for surgery or have recently undergone surgery. Sunitinib Bluefish may affect wound healing. The medicine is usually discontinued before surgery. Your doctor will decide when to restart Sunitinib Bluefish.
• A dental examination is recommended before starting treatment with Sunitinib Bluefish.
  • If you have or have had mouth pain, tooth or jaw pain, swelling or ulceration in the mouth, numbness or heaviness in the jaw, or loose teeth, inform your oncologist and dentist immediately.
  • If you require invasive dental treatment or oral surgery, inform your dentist that you are taking Sunitinib Bluefish, especially if you are also taking or have previously taken intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone problems and may be used for other conditions.
• If you have or have had skin and subcutaneous tissue disorders. While taking this medicine, pyoderma gangrenosum (painful skin ulceration) or necrotizing fasciitis (rapidly spreading infection of the skin and/or soft tissues, which may be life-threatening) may occur. Contact your doctor immediately if you develop signs of infection around skin lesions, including fever, pain, redness, swelling, or discharge of pus or blood. These conditions usually resolve after discontinuation of sunitinib. Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed during treatment, which initially appear as red, target-like or circular skin patches, often with central blisters. The rash may progress to extensive blistering or skin peeling and may be life-threatening. If you develop a rash or any of the above-mentioned skin symptoms, contact your doctor immediately.
• If you have or have had seizures. Inform your doctor as soon as possible if you develop high blood pressure, headache, or vision loss.
• If you have diabetes. Patients with diabetes should regularly monitor blood glucose levels to determine whether adjustment of antidiabetic medication is needed to minimize the risk of hypoglycaemia. Inform your doctor promptly if you experience symptoms of low blood sugar (fatigue, palpitations, excessive sweating, hunger, or loss of consciousness).

Children and adolescents
Sunitinib Bluefish is not recommended for patients under 18 years of age.

Sunitinib Bluefish and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those without a prescription, and any medicines you plan to take.
Some medicines may affect the concentration of Sunitinib Bluefish in the body. 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 HIV infection;
• dexamethasone – a corticosteroid used in various conditions (such as allergic 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 disorders.

Sunitinib Bluefish with food and drink
Do not drink grapefruit juice during treatment with Sunitinib Bluefish.

Pregnancy and breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before taking this medicine.
Women of childbearing potential should use an effective method of contraception during treatment with Sunitinib Bluefish.
Women who are breastfeeding should inform their doctor. Breastfeeding is not recommended during treatment with Sunitinib Bluefish.

Driving and using machines
Exercise caution when driving or operating machinery if you experience dizziness or significant fatigue.

Sunitinib Bluefish contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. it is considered "sodium-free".

3. How to take Sunitinib Bluefish

This medicine should always be taken as prescribed by your doctor. If in doubt,
consult your doctor.
Your doctor will prescribe the appropriate dose for you, depending on the type of tumour.
For patients being treated for:

• GIST or MRCC, the usual dose is 50 mg once daily for 28 days (4 weeks), followed by a 14-day (2-week) treatment-free break, in 6-week treatment cycles.
• pNET, the usual dose is 37.5 mg once daily continuously.

Your doctor will determine the appropriate dose for you and when treatment with
Sunitinib Bluefish should end.
Sunitinib Bluefish may be taken with or without food.
Taking more Sunitinib Bluefish than prescribed
If too many capsules have been taken, contact your doctor immediately.
Medical intervention may be necessary.
Missing a dose of Sunitinib Bluefish
Do not take a double dose to make up for a missed dose.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
You should contact a doctor immediately if the patient experiences any of the following adverse
reactions (see also Important information before taking Sunitinib Bluefish):
Heart diseases. Inform the doctor if the patient feels very tired, experiences shortness of
breath or swelling of the feet and ankles. These may be symptoms of heart problems, which may
include heart failure and problems with the heart muscle (cardiomyopathy).
Lung diseases or breathing difficulties. Inform the doctor if the patient develops cough, chest
pain, sudden onset of breathlessness or coughing up blood. These may be symptoms of a condition
called pulmonary embolism, which occurs when blood clots travel to the lungs.
Kidney function disorders. Inform the doctor if the patient experiences changes in frequency
or absence of urination, which may be symptoms of kidney failure.
Bleeding. Inform the doctor if the patient experiences any of the following symptoms or severe
bleeding during treatment with Sunitinib Bluefish: abdominal pain and swelling; vomiting blood;
black, tarry stools; blood in the urine; headache or changes in consciousness; coughing up blood or
bloody sputum from the lungs or airways.
Tumour lysis leading to intestinal perforation. Inform the doctor if the patient experiences
severe abdominal pain, fever, nausea, vomiting, blood in the stool or changes in bowel function.
Other adverse reactions of Sunitinib Bluefish may include:
Very common: may affect more than 1 in 10 people

• Decreased platelet, red blood cell and (or) white blood cell counts (e.g. neutrophils).
• Shortness of breath.
• Hypertension.
• Extreme fatigue, loss of strength.
• Swelling due to fluid accumulation under the skin and around the eyes, deep allergic rash.
• Pain and (or) irritation in the mouth, painful ulceration and (or) inflammation and (or) dryness of the mouth, taste disturbances, gastric disturbances, nausea, vomiting, diarrhoea, constipation, abdominal pain and (or) swelling, loss of and (or) reduced appetite.
• Decreased thyroid activity (hypothyroidism).
• Dizziness.
• Headache.
• Nosebleeds.
• Back pain, joint pain.
• Pain in arms and legs.
• Yellowing of the skin and (or) skin discoloration, excessive skin pigmentation, hair colour 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 embolism or narrowing of the coronary arteries.
• Chest pain.
• Reduced volume of blood pumped by the heart.
• Fluid retention, including in the lung area.
• Infections.
• Complication following severe infection (blood infection), which may lead to tissue damage, organ failure and death.
• Low blood sugar levels (see section 2).
• Protein loss in urine, sometimes causing swelling.
• Flu-like syndrome.
• Abnormal blood test results, including pancreatic and liver enzymes.
• High levels of uric acid in the blood.
• Haemorrhoids, rectal pain, bleeding gums, difficulty swallowing or loss of swallowing ability.
• Burning or painful sensation of the tongue, inflammation of the mucous membrane of the gastrointestinal 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 mucous membrane, sensation of nasal congestion.
• Excessive tearing.
• Skin sensory disturbances, itching, skin peeling and inflammation, blisters, acne, nail discolouration, hair loss.
• Sensory disturbances in the limbs.
• Disorders related to increased or decreased sensitivity, especially to touch.
• Heartburn.
• Dehydration.
• Hot flushes.
• Abnormal urine colour.
• Depression.
• Chills.

Uncommon: may affect up to 1 in 100 people

• Life-threatening soft tissue infections, including the anogenital area (see section 2).
• Stroke.
• Myocardial infarction caused by interruption or reduction of blood supply to the heart.
• Changes in electrical function or rhythm disturbances of the heart.
• Presence of fluid around the heart (pericardial effusion).
• Liver failure.
• Abdominal pain caused by inflammation of the pancreas.
• Tumour lysis leading to intestinal perforation.
• Inflammation (swelling or redness) of the gallbladder with or without gallstones.
• Formation of abnormal connections between one body cavity and another or to the skin.
• Mouth pain, tooth and (or) jaw pain, swelling or ulceration of the mouth, numbness or heaviness in the jaw, or tooth mobility. These may be symptoms of jaw bone damage (osteonecrosis), see section 2.
• Excessive production of thyroid hormones leading to increased resting metabolism.
• Impaired wound healing after surgical procedures.
• Increased activity of muscle enzyme (creatine phosphokinase) in blood.
• Excessive reaction to allergens, including hay fever, skin rash, itching, hives, swelling of any body part, and breathing difficulties.
• Inflammation of the large intestine (colitis, ischaemic colitis).

Rare: may affect up to 1 in 1000 people

• Severe reaction affecting the skin and (or) mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).
• Tumour lysis syndrome, a group of metabolic complications that may occur during cancer treatment. These complications are caused by products of degenerating tumour cells and may include: nausea, shortness of breath, irregular heartbeat, muscle spasms, 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 kidney changes and acute kidney failure.
• Abnormal muscle breakdown which may cause kidney disease (rhabdomyolysis).
• Abnormal changes in the brain which may cause a syndrome of symptoms including headache, confusion, seizures and vision loss (reversible posterior leukoencephalopathy syndrome).
• Painful skin ulceration (pyoderma gangrenosum).
• Hepatitis.
• Inflammation of the thyroid gland.
• Damage to the smallest blood vessels called thrombotic microangiopathy.

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

• Enlargement and weakening of the blood vessel wall or rupture of the blood vessel wall (aneurysm and arterial dissection).
• Lack of energy, confusion, drowsiness, loss of consciousness or coma – these symptoms may indicate toxic effects of high blood ammonia levels on the brain (hyperammonaemic encephalopathy).

Reporting of adverse reactions
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or
pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of
Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices
and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Sunitinib Bluefish
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, blister pack and bottle after:
Expiry (EXP). The expiry date refers to the last day of the stated month.
Store in the original packaging to protect from light.
Do not use this medicine if the packaging is damaged or if there are signs of prior opening.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Sunitinib Bluefish contains

• The active substance is sunitinib. Each capsule contains 12.5 mg, 25 mg or 50 mg of sunitinib.
• The other ingredients are:
  • Capsule contents: microcrystalline cellulose (type 200), mannitol (E 421), sodium croscarmellose, povidone K-30, magnesium stearate
  • Capsule shell: 12.5 mg: gelatin, iron oxide red (E 172) and titanium dioxide (E 171). 25 mg and 50 mg: gelatin, iron oxide red (E 172), iron oxide yellow (E 172), iron oxide black (E 172) and titanium dioxide (E 171)
  • Printing ink: shellac, titanium dioxide (E 171) and propylene glycol

What Sunitinib Bluefish looks like and contents of the pack
Sunitinib Bluefish 12.5 mg, hard capsules:
Hard capsules of size "4" with an orange cap and an orange body, printed in white ink with "SB 12.5" and a white line on the body, containing granules

• ranging from yellow to orange, with a nominal length of approximately 14.3 mm.

Sunitinib Bluefish 25 mg, hard capsules:
Hard capsules of size "3" with a caramel cap and an orange body, printed in white ink with "SB 25" and a white line on the body, containing granules

• ranging from yellow to orange, with a nominal length of approximately 15.9 mm.

Sunitinib Bluefish 50 mg, hard capsules:
Hard capsules of size "1" with a caramel cap and a caramel body, printed in white ink with "SB 50" and a white line on the body, containing granules – ranging from yellow to orange, with a nominal length of approximately 19.4 mm.
Sunitinib Bluefish 12.5 mg, 25 mg and 50 mg, hard capsules are available in blister packs and bottles, with a container containing silica gel as a desiccant, in a cardboard box.
Pack size: 28 capsules

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Bluefish Pharmaceuticals AB
P.O. Box 49013
100 28 Stockholm
Sweden
Tel. +46 8 51 91 16 00

Manufacturer
Pharmacare Premium Ltd
HHF003 Hal Far Industrial Estate
Birzebbugia, BBG3000
Malta
Genepharm S.A.
18 km Marathonos Avenue
153 51 Pallini Attiki
Greece

This medicinal product is authorised in the European Economic Area under the following names: