Package leaflet: Information for the user

Sunitinib Pharmascience, 12.5 mg, hard capsules
Sunitinib Pharmascience, 25 mg, hard capsules
Sunitinib Pharmascience, 37.5 mg, hard capsules
Sunitinib Pharmascience, 50 mg, hard capsules
Sunitinibum
Please read the entire leaflet carefully before 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 further questions, please ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents:

What Sunitinib Pharmascience is and what it is used for
Important information before taking Sunitinib Pharmascience
How to take Sunitinib Pharmascience
Possible side effects
How to store Sunitinib Pharmascience
Contents of the pack and other information

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

Sunitinib Pharmascience contains sunitinib as the active substance, which is a protein kinase inhibitor. It is used in the treatment of cancers. It inhibits the activity of a specific group of proteins known to be involved in the growth and spread of cancer cells.

Sunitinib Pharmascience 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;
Progressive, unresectable pancreatic neuroendocrine tumours (pNET) (tumours arising from hormone-secreting cells in the pancreas).

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

2. Important information before taking Sunitinib Pharmascience

When not to take Sunitinib Pharmascience

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

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

If high blood pressure is present. Sunitinib Pharmascience may increase blood pressure. Your doctor may monitor your blood pressure during treatment with Sunitinib Pharmascience, and if necessary, you may be treated with antihypertensive medications.
If there are or have been blood disorders, bleeding or bruising. Treatment with Sunitinib Pharmascience may increase the risk of bleeding or alter the count of certain blood cells, potentially causing anaemia or affecting blood clotting ability. If the patient is taking warfarin or acenocoumarol, anticoagulant medicines used to prevent blood clots, the risk of bleeding may increase. Inform your doctor about any bleeding episodes during treatment with Sunitinib Pharmascience.
If there are heart-related disorders. Sunitinib Pharmascience may cause heart problems. Inform your doctor if the patient experiences severe fatigue, shortness of breath, or swelling in the feet or ankles.
If there are heart rhythm disorders. Sunitinib Pharmascience may cause irregular heart rhythms. During treatment, your doctor may perform an electrocardiogram (ECG) to monitor for such disturbances. Inform your doctor if the patient experiences dizziness, fainting, or irregular heartbeat while taking Sunitinib Pharmascience.
If the patient has recently experienced venous and/or arterial thrombosis (types of blood vessels), including stroke, myocardial infarction, embolism, or thrombosis. Contact your doctor immediately if, during treatment with Sunitinib Pharmascience, the patient develops 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.
If the patient has or has had an aneurysm (a weakened and enlarged blood vessel wall) or arterial dissection.
If there are or have been in the past microvascular damage known as thrombotic microangiopathy. Inform your doctor if the patient develops fever, fatigue, bruising, bleeding, swelling, confusion, vision loss, or seizures.
If there are thyroid disorders. Sunitinib Pharmascience may cause thyroid dysfunction. Inform your doctor if the patient feels unusually tired, feels colder than usual, or experiences voice changes during treatment. Your doctor should check thyroid function before starting Sunitinib Pharmascience and regularly during treatment. If the thyroid gland does not produce enough hormone, the patient may require thyroid hormone replacement therapy.
If there are or have been in the past disorders of the pancreas or gallbladder. Inform your doctor if the patient experiences any of the following symptoms: stomach pain (upper abdomen), nausea, vomiting, or fever. These may be signs of pancreatitis or cholecystitis.
If there are or have been in the past liver function disorders. Inform your doctor if, during treatment with Sunitinib Pharmascience, the patient develops any of the following signs of liver problems: itching, yellowing of the eyes or skin (jaundice), dark urine, or pain or discomfort in the right upper abdomen. Your doctor should order blood tests to monitor liver function before starting treatment, during treatment, and whenever clinically indicated.
If there are or have been in the past kidney function disorders. Your doctor will monitor kidney function.
If the patient is scheduled for surgery or has recently undergone surgery. Sunitinib Pharmascience may impair wound healing. This medicine is usually discontinued before surgical procedures. Your doctor will decide when to restart Sunitinib Pharmascience.
The patient is advised to have a dental examination before starting treatment with Sunitinib Pharmascience:
- If the patient experiences 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 invasive dental treatment or a dental surgical procedure is required, the patient must inform the dentist about taking Sunitinib Pharmascience, especially if also taking or having previously taken intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone problems and may be taken for other conditions.
If there are or have been in the past skin and subcutaneous tissue disorders. During treatment with 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 the patient develops signs of infection around skin lesions, including fever, pain, redness, swelling, or pus or blood discharge. These conditions usually resolve after discontinuation of Sunitinib Pharmascience. Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed during treatment, which initially appear as red, target-shaped or circular spots, often with centrally located blisters. The rash may progress to extensive blistering or skin peeling and may be life-threatening. If the patient develops a rash or any of the above skin symptoms, seek medical attention immediately.
If there are or have been seizures. Inform your doctor as soon as possible if the patient develops high blood pressure, headache, or vision loss.
If the patient has diabetes. Blood glucose levels should be monitored regularly in diabetic patients to assess whether adjustment of antidiabetic medication is needed to minimize the risk of hypoglycaemia. Inform your doctor promptly if the patient experiences symptoms of low blood sugar (fatigue, palpitations, excessive sweating, hunger, or loss of consciousness).

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

Sunitinib Pharmascience and other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including over-the-counter medicines and herbal supplements, as well as any medicines the patient plans to take.
Some medicines may affect the concentration of Sunitinib Pharmascience in the body. Inform your doctor if the patient is taking medicines containing 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.

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

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Women of childbearing potential should use an effective method of contraception during treatment with Sunitinib Pharmascience.
Women who are breastfeeding should inform their doctor. Breastfeeding is not recommended during treatment with Sunitinib Pharmascience.

Driving and operating machinery
If the patient experiences dizziness or significant fatigue, exercise caution when driving or operating machinery.

Sunitinib Pharmascience contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, meaning it is considered "sodium-free".

3. How to take Sunitinib Pharmascience
Always take this medicine exactly as prescribed by your doctor. If in doubt, consult your doctor.
Your doctor will prescribe the dose appropriate for the individual patient, depending on the type of tumour. If the patient is 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 period, in 6-week treatment cycles.
If the patient is being treated for pNET, the usual dose is 37.5 mg once daily continuously.
Your doctor will determine the appropriate dose for the individual patient and the timing for stopping treatment with Sunitinib Pharmascience.
Sunitinib Pharmascience may be taken with or without food.

Taking more Sunitinib Pharmascience than prescribed
If the patient accidentally takes more capsules than prescribed, contact your doctor immediately. Urgent medical attention may be required.

Missing a dose of Sunitinib Pharmascience
Do not take a double dose to make up for a missed dose.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
You should contact a doctor immediately if any of the following adverse reactions occur in the patient (see also Important information before taking
Sunitinib Pharmascience ):
Heart disorders . Tell the doctor if the patient feels very tired, has shortness of breath,
or swelling of the feet and ankles. These may be symptoms of heart problems, including heart failure and
disorders of the heart muscle (cardiomyopathy).
Lung disorders or breathing problems . Tell the doctor if the patient develops
cough, 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 travel to the lungs.
Kidney function disorders . Tell the doctor if the patient experiences changes in
urination frequency or absence of urination, which may be symptoms of kidney failure.
Bleeding . Tell the doctor if the patient experiences any of the following symptoms or has severe bleeding during treatment with Sunitinib Pharmascience: stomach (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 . Tell 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 Pharmascience may include:
Very common: may occur in more than 1 in 10 people

decrease in the number of platelets, red blood cells, and (or) white blood cells (e.g. neutrophils)
shortness of breath
high blood pressure
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, stomach disturbances, nausea, vomiting, diarrhoea, constipation, abdominal pain and (or) swelling, loss of and (or) reduced appetite
reduced 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 color changes, rash on palms and soles of feet, rash, dry skin
cough
fever
difficulty sleeping.

Common: may occur in no more than 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 amount of blood pumped by the heart
fluid retention, including in the lung area
infections
complication following a severe infection (blood infection), which may lead to tissue damage, organ failure, and death
low blood sugar levels (see section 2)
loss of protein in the 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 from gums, difficulty or inability to swallow
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 discoloration, hair loss
sensory disturbances in the limbs
disturbances related to increased or decreased sensitivity, especially to touch
heartburn
dehydration
hot flushes
abnormal urine colour
depression
chills.

Uncommon: may occur in no more than 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 due to 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 loose teeth. 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 the blood
excessive reaction to allergens, including hay fever, skin rash, itching, urticaria, swelling of any body part, and breathing difficulties
inflammation of the large intestine (colitis, ischemic colitis).

Rare: may occur in no more than 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 the products of disintegrating tumour 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 the blood), which may lead to kidney changes and acute kidney failure
abnormal muscle breakdown that may cause kidney disease (rhabdomyolysis)
abnormal changes in the brain that may cause a syndrome 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)

widening or bulging of the aorta or aortic wall tear (aortic aneurysm or aortic dissection)

Reporting of adverse reactions
If any symptoms of adverse reactions occur, including any adverse reactions not listed
in this leaflet, tell your doctor or pharmacist. Adverse reactions can be reported
directly to the Department of Monitoring 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 responsible entity.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Sunitinib Pharmascience

Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, bottle, and blister pack following: Expiry date (EXP). The expiry date refers to the last day of the stated month.
There are no special storage instructions for this medicine.
Do not use this medicine if the patient notices that the packaging is damaged or if there are signs of prior opening.

Medicines must not be disposed of via wastewater or household waste. Ask a pharmacist how to properly dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Sunitinib Pharmascience contains
Sunitinib Pharmascience, 12.5 mg, hard capsules
The active substance is sunitinib. Each capsule contains sunitinib hydrochloride equivalent to
12.5 mg of sunitinib. The other ingredients are:
Capsule contents: mannitol, sodium croscarmellose, povidone (K25) and magnesium stearate.
Capsule shell: gelatin, iron oxide red (E 172) and titanium dioxide (E 171).
Black ink: shellac, propylene glycol, iron oxide black (E 172), concentrated ammonium hydroxide
and potassium hydroxide.

Sunitinib Pharmascience, 25 mg, hard capsules
The active substance is sunitinib. Each capsule contains sunitinib hydrochloride equivalent to
25 mg of sunitinib. The other ingredients are:
Capsule contents: mannitol, sodium croscarmellose, povidone (K25) and magnesium stearate.
Capsule shell: gelatin, iron oxide red (E 172), titanium dioxide (E 171) and iron oxide yellow (E 172).
Black ink: shellac, propylene glycol, iron oxide black (E 172), concentrated ammonium hydroxide
and potassium hydroxide.

Sunitinib Pharmascience, 37.5 mg, hard capsules
The active substance is sunitinib. Each capsule contains sunitinib hydrochloride equivalent to
37.5 mg of sunitinib. The other ingredients are:
Capsule contents: mannitol, sodium croscarmellose, povidone (K25) and magnesium stearate.
Capsule shell: gelatin, titanium dioxide (E 171) and iron oxide yellow (E 172).
Black ink: shellac, propylene glycol (E1520), iron oxide black (E 172), concentrated ammonium hydroxide
and potassium hydroxide.

Sunitinib Pharmascience, 50 mg, hard capsules
The active substance is sunitinib. Each capsule contains sunitinib hydrochloride equivalent to
50 mg of sunitinib. The other ingredients are:
Capsule contents: mannitol, sodium croscarmellose, povidone (K25) and magnesium stearate.
Capsule shell: gelatin, iron oxide red (E 172), titanium dioxide (E 171) and iron oxide yellow (E 172).
Black ink: shellac, propylene glycol, iron oxide black (E 172), concentrated ammonium hydroxide
and potassium hydroxide.

What Sunitinib Pharmascience looks like and contents of the pack
Sunitinib Pharmascience 12.5 mg is available as hard gelatin capsules, size 4, with a Swedish orange cap and body, radially printed in black with "SUN 12.5 mg" on the body, containing orange powder.
Sunitinib Pharmascience 25 mg is available as hard gelatin capsules, size 3, with an orange cap and Swedish orange body, radially printed in black with "SUN 25 mg" on the body, containing orange powder.
Sunitinib Pharmascience 37.5 mg is available as hard gelatin capsules, size 3, with ivory cap and body, radially printed in black with "SUN 37.5 mg" on the body, containing orange powder.
Sunitinib Pharmascience 50 mg is available as hard gelatin capsules, size 2, with an orange cap and body, radially printed in black with "SUN 50 mg" on the body, containing orange powder.

Sunitinib Pharmascience is available in cardboard boxes containing 28 capsules packed in PVC/PVAC (PVC/PCTFE)/Aluminium blisters.
Sunitinib Pharmascience 50 mg is also available in cardboard boxes containing 28 capsules packed in PVC/PVDC/Aluminium blisters.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Pharmascience International Limited.
Lampousas 1
1095 Nicosia
Cyprus

Manufacturer
Bluepharma - Indústria Farmacêutica, S.A.
S. Martinho do Bispo
3045-016 Coimbra
Portugal

This medicinal product is authorised for sale in the EEA Member States under the following names:
Portugal: Sunitinib Bluepharma
Cyprus: Sunitinib Pharmascience 12.5 mg hard capsules
Sunitinib Pharmascience 25 mg hard capsules
Sunitinib Pharmascience 37.5 mg hard capsules
Sunitinib Pharmascience 50 mg hard capsules
Bulgaria: Sunitinib Pharmascience 12.5 mg hard capsules
Sunitinib Pharmascience 25 mg hard capsules
Sunitinib Pharmascience 37.5 mg hard capsules
Sunitinib Pharmascience 50 mg hard capsules
Croatia: Sunitinib Pharmascience 12.5 mg tvrde kapsule
Sunitinib Pharmascience 25 mg tvrde kapsule
Sunitinib Pharmascience 37.5 mg tvrde kapsule
Sunitinib Pharmascience 50 mg tvrde kapsule
Hungary: Sunitinib Pharmascience 12.5 mg kemény kapszula
Sunitinib Pharmascience 25 mg kemény kapszula
Sunitinib Pharmascience 37.5 mg kemény kapszula
Sunitinib Pharmascience 50 mg kemény kapszula
Poland: Sunitinib Pharmascience
Slovenia: Sunitinib Pharmascience 12.5 mg trde kapsule
Sunitinib Pharmascience 25 mg trde kapsule
Sunitinib Pharmascience 37.5 mg trde kapsule
Sunitinib Pharmascience 50 mg trde kapsule