Sunitinib glenmark

Package leaflet: Information for the user

Sunitinib Glenmark, 12.5 mg, hard capsules
Sunitinib Glenmark, 25 mg, hard capsules
Sunitinib Glenmark, 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. 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 symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

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

Sunitinib Glenmark contains the active substance sunitinib, which is a protein kinase inhibitor.
This medicine is used in the treatment of cancers because it inhibits the activity of a specific group of proteins known to be involved in the growth and spread of cancer cells.
Sunitinib Glenmark is used in adult patients for the treatment of the following cancers:

• Gastrointestinal stromal tumours (GIST), a type of stomach and intestinal tumour, when imatinib is ineffective (another anticancer medicine) or when the patient cannot take imatinib.
• 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-producing cells of the pancreas) that are growing or cannot be surgically removed.

If you have any questions about how Sunitinib Glenmark works or why your doctor has prescribed it for you, please consult your doctor.

2. Important information before using Sunitinib Glenmark

When not to use Sunitinib Glenmark

• 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 Glenmark, discuss the following with your doctor or
pharmacist:

• If the patient has high blood pressure. Sunitinib Glenmark may increase blood pressure. Your doctor may monitor your blood pressure during treatment with Sunitinib Glenmark and, if necessary, may prescribe antihypertensive medicines.

• If the patient has or has had blood disorders, bleeding or bruising. Treatment with Sunitinib Glenmark may increase the risk of bleeding or may alter the number of certain blood cells, which could lead to anaemia or affect the blood’s ability to clot. If the patient is taking warfarin or acenocoumarol, anticoagulant medicines used to prevent blood clots, the risk of bleeding may be higher. Inform your doctor about any bleeding episodes occurring during treatment with Sunitinib Glenmark.

• If the patient has heart conditions. Sunitinib Glenmark may cause heart problems. Inform your doctor if the patient experiences significant fatigue, shortness of breath, or swelling of the feet or ankles.

• If the patient has heart rhythm disorders. Sunitinib Glenmark may cause heart rhythm disturbances. During treatment with Sunitinib Glenmark, your doctor may perform an electrocardiogram (ECG) to assess these disturbances. Inform your doctor if the patient experiences dizziness, fainting, or irregular heartbeat during treatment with Sunitinib Glenmark.

• If the patient has 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 Glenmark, the patient experiences 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 the patient has or has previously had an aneurysm (a bulge and weakening of the blood vessel wall) or a tear in the blood vessel wall.

• If the patient has or has previously had damage to the smallest blood vessels known as thrombotic microangiopathy. Inform your doctor if the patient develops fever, fatigue, weakness, bruising, bleeding, swelling, confusion, vision loss or seizures.

• If the patient has thyroid disorders. Sunitinib Glenmark may cause thyroid problems. Inform your doctor if, during treatment with Sunitinib Glenmark, the patient becomes easily fatigued, feels colder than others, or experiences hoarseness. Your doctor should check the patient’s thyroid function before starting treatment with Sunitinib Glenmark and regularly during treatment. If the thyroid gland does not produce enough thyroid hormones, the patient may require hormone replacement therapy.

• If the patient has or has previously had pancreatic disorders or gallbladder disease. Inform your doctor if the patient experiences any of the following symptoms: stomach pain (upper abdomen), nausea, vomiting or fever. These may be symptoms of pancreatitis or gallbladder inflammation.

• If the patient has or has previously had liver disease. Inform your doctor if, during treatment with Sunitinib Glenmark, the patient develops any of the following signs of liver dysfunction: itching, yellowing of the whites of the eyes or skin (jaundice), dark urine, or pain or discomfort in the upper right abdomen. Your doctor should order blood tests to monitor liver function before starting treatment with Sunitinib Glenmark, during treatment, and whenever clinically indicated.

• If the patient has or has previously had kidney disease. Your doctor will monitor the patient’s kidney function.

• If the patient is scheduled for surgery or has recently undergone surgery. Sunitinib Glenmark may affect wound healing. Treatment with Sunitinib Glenmark is usually discontinued before surgery.
  Your doctor will decide when to restart treatment with Sunitinib Glenmark.

• Your doctor may recommend a dental examination before starting treatment with Sunitinib Glenmark.

• If the patient experiences pain in the mouth, tooth or jaw pain and/or swelling, mouth ulcers, numbness or heaviness in the jaw, or loose teeth, inform the treating doctor and dentist immediately.

• If the patient requires invasive dental treatment or oral surgery, inform the dentist about treatment with Sunitinib Glenmark, especially if the patient is also taking or has previously taken intravenous bisphosphonates. Bisphosphonates are medicines used to prevent bone-related complications and may be used for other medical conditions.

• If the patient has or has previously had skin or subcutaneous tissue disorders. During treatment with this medicine, pyoderma gangrenosum (painful skin ulceration) or necrotizing fasciitis (a rapidly spreading and potentially life-threatening infection of the skin and/or soft tissues) may occur. Contact your doctor immediately if signs of infection develop around a skin lesion, including fever, pain, redness, swelling, or pus or blood discharge. These conditions usually resolve after discontinuation of sunitinib. Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed during sunitinib treatment. These initially appear as red, target-like or circular skin rashes, 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 these skin symptoms, seek medical advice immediately.

• If the patient has or has previously had seizures. Inform your doctor immediately 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 immediately if any symptoms of low blood sugar occur (feeling tired, palpitations, sweating, hunger, or loss of consciousness).

Children and adolescents
Sunitinib Glenmark is not recommended for use in patients under 18 years of age.
Sunitinib Glenmark and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including those obtained without a prescription, as well as any medicines the patient plans to take.
Some medicines may affect the concentration of Sunitinib Glenmark in the patient’s 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 in the treatment of HIV infection
• dexamethasone – a corticosteroid used in various conditions (such as allergic reactions and/or respiratory disorders or skin diseases)
• phenytoin, carbamazepine, phenobarbital – used to treat epilepsy and other neurological disorders
• herbal medicines containing St John’s wort (Hypericum perforatum) – used to treat depression and anxiety

Sunitinib Glenmark with food and drink
Do not drink grapefruit juice during treatment with Sunitinib Glenmark.
Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a baby, 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 Glenmark.
Inform your doctor if the patient is breastfeeding. Breastfeeding is not recommended during treatment with Sunitinib Glenmark.
Driving and using machines
If the patient experiences dizziness or significant fatigue, exercise particular caution when driving or operating machinery.
Sunitinib Glenmark contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. the medicine is considered "sodium-free".

3. How to take Sunitinib Glenmark

This medicine should always be taken exactly as prescribed by the doctor. If in doubt, consult
your doctor.
The doctor will prescribe the dose appropriate for the 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 break, in 6-week treatment cycles.
• pNET: the usual dose is 37.5 mg once daily, taken continuously.

The doctor will determine the appropriate dose for the patient and when treatment with Sunitinib
Glenmark should end.
Sunitinib Glenmark may be taken with food or on an empty stomach.
Taking more Sunitinib Glenmark than prescribed
If the patient accidentally takes more capsules than recommended, contact the doctor immediately,
as the patient may require urgent medical care.
Missing a dose of Sunitinib Glenmark
Do not take a double dose to make up for a missed dose.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

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 these
adverse reactions (see also Important information before using Sunitinib Glenmark):
Heart diseases. Tell the doctor if the patient experiences severe fatigue, shortness of breath, or swelling of the feet or ankles. These may be symptoms of heart problems, which may include heart failure and heart muscle problems (cardiomyopathy).
Lung diseases or breathing disorders. 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 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 severe bleeding during treatment with Sunitinib Glenmark: stomach (abdominal) pain or 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 Glenmark may include:
Very common: may occur in more than 1 in 10 patients

• decrease in the 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 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 oral mucosa, taste disturbances, indigestion, nausea, vomiting, diarrhoea, constipation, abdominal pain and/or swelling, loss of appetite or reduced appetite
• reduced thyroid function (hypothyroidism)
• dizziness
• headache
• nosebleeds
• back pain, joint pain
• pain in hands and legs
• yellowing of the skin and/or skin discoloration, excessive skin pigmentation, hair color changes, rash on palms and soles, skin rash, dry skin
• cough
• fever
• difficulty sleeping

Common: may occur in no more than 1 in 10 patients

• blood clots in blood vessels
• inadequate blood supply to the heart due to blockage or narrowing of the coronary arteries
• chest pain
• reduced amount of blood pumped by the heart
• fluid accumulation, including around the lungs
• infections
• complications of severe infections (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
• influenza-like syndrome
• abnormal blood test results, including abnormal pancreatic and liver enzyme activity
• high levels of uric acid in the blood
• haemorrhoids, anal pain, bleeding gums, difficulty swallowing or loss of swallowing ability
• burning or painful sensation of the tongue, inflammation of the gastrointestinal mucosa, 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, nasal congestion
• excessive tearing
• skin sensation disorders, itching, skin peeling and inflammation, blisters, acne, nail discoloration, hair loss
• sensory disturbances in the limbs
• disorders related to increased or decreased sensitivity, especially to touch
• heartburn
• dehydration
• hot flashes
• abnormal urine color
• depression
• chills

Uncommon: may occur in no more than 1 in 100 patients

• life-threatening soft tissue infections, including around the anus and genital organs (see section 2)
• stroke
• myocardial infarction caused by interruption or reduction of blood supply to the heart
• changes in electrical function or irregular heart rhythm
• 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 loose teeth. These may be symptoms of jaw bone damage (osteonecrosis), see section 2
• excessive production of thyroid hormones leading to increased energy consumption by the body at rest
• impaired healing of surgical wounds
• increased activity of muscle enzyme (creatine phosphokinase) in the blood
• excessive reaction to allergens including hay fever, skin rash, skin itching, urticaria, swelling of various body parts, and breathing difficulties
• inflammation of the large intestine (colitis, ischemic colitis)

Rare: (may occur in no more than 1 in 1,000 patients)

• severe skin and/or mucous membrane reaction (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 released from dying 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 phosphorus, and low calcium levels in the blood), which may lead to kidney changes and acute kidney failure

• abnormal muscle breakdown that may lead to kidney disease (rhabdomyolysis)

• abnormal changes in the brain that may cause a syndrome of symptoms including headache, confusion, seizures, and vision loss (reversible posterior leukoencephalopathy syndrome)

• painful skin ulceration (pyoderma gangrenosum)

• hepatitis

• thyroiditis

• damage to the smallest blood vessels called thrombotic microangiopathy

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 symptoms occur, including any adverse symptoms not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at 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 this medicine.

5. How to store Sunitinib Glenmark

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton or
blister after: EXP. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Do not use this medicine if the packaging is damaged or if the tamper-evident seal has
been broken.
Medicines must 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 Sunitinib Glenmark contains

• The active substance is sunitinib.
  Sunitinib Glenmark 12.5 mg hard capsules
  Each capsule contains 12.5 mg of sunitinib.
  Sunitinib Glenmark 25 mg hard capsules
  Each capsule contains 25 mg of sunitinib.
  Sunitinib Glenmark 50 mg hard capsules
  Each capsule contains 50 mg of sunitinib.

• Other ingredients are:
  Capsule contents: microcrystalline cellulose, mannitol, sodium croscarmellose, povidone K30, magnesium stearate.
  Sunitinib Glenmark 12.5 mg hard capsules

• Capsule shell: iron oxide red (E 172), titanium dioxide (E 171), gelatin.

• White ink: shellac, titanium dioxide (E 171), propylene glycol.

Sunitinib Glenmark 25 mg hard capsules

• Capsule shell: iron oxide black (E 172), iron oxide red (E 172), iron oxide yellow (E 172), titanium dioxide (E 171), gelatin.
• White ink: shellac, titanium dioxide (E 171), propylene glycol.

Sunitinib Glenmark 50 mg hard capsules

• Capsule shell: iron oxide black (E 172), iron oxide red (E 172), iron oxide yellow (E 172), titanium dioxide (E 171), gelatin.
• White ink: shellac, titanium dioxide (E 171), propylene glycol.

What Sunitinib Glenmark looks like and contents of the pack
Sunitinib Glenmark 12.5 mg hard capsules (capsules)
Size 4 (approximately 14.3 mm in length) gelatin capsules with an orange cap and an orange body, marked with "12.5 mg" in white ink on the body, containing yellow to orange granules.
Sunitinib Glenmark 25 mg hard capsules (capsules)
Size 3 (approximately 15.9 mm in length) gelatin capsules with a caramel cap and an orange body, marked with "25 mg" in white ink on the body, containing yellow to orange granules.
Sunitinib Glenmark 50 mg hard capsules (capsules)
Size 1 (approximately 19.4 mm in length) gelatin capsules with a caramel cap and a caramel body, marked with "50 mg" in white ink on the body, containing yellow to orange granules.
Sunitinib Glenmark hard capsules are available in perforated single-dose blisters containing 28 hard capsules.

Marketing Authorisation Holder
Glenmark Pharmaceuticals s.r.o.
Hvězdova 1716/2B
140 78 Prague 4
Czech Republic

Manufacturer
Remedica Ltd
Aharnon Street, Limassol Industrial Estate
3056 Limassol
Cyprus
Glenmark Pharmaceuticals s.r.o.
Fibichova 143
566 17 Vysoké Mýto
Czech Republic

For further information, contact the local representative of the Marketing Authorisation Holder:
Glenmark Pharmaceuticals Sp. z o.o.
ul. Dziekonskiego 3
00-728 Warsaw
Email: [email protected]