Sunitinib IPI 12.5, 25, and 50 mg

1. Dosage:

- 12.5 mg

- 25 mg

- 50 mg

2. What Sunitinib IPI is and what is it used for:

Sunitinib IPI contains the active substance sunitinib, which is a protein inhibitor. It is used to treat cancer by preventing the activity of a special group of proteins which are known to be involved in the growth and spread of cancer cells.

Sunitinib IPI is used to treat adults with the following types of cancer:

- Gastrointestinal stromal tumour (GIST), a type of cancer of the stomach and bowel, where imatinib (another anticancer medicine) no longer works or you 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 the hormoneproducing cells in the pancreas) that have progressed or cannot be removed with surgery. If you have any questions about how Sunitinib IPI works or why this medicine has been prescribed to you, ask your doctor.

3. What you need to know before you take Sunitinib IPI:

Do not take Sunitinib IPI if you are allergic to Sunitinib or any of the other ingredients of Sunitinib IPI.

Sunitinib IPI is not recommended for people aged under 18.

Other Medicines and Sunitinib IPI: Tell your doctor or if you are taking, have recently taken, or might take any other medicines.

Sunitinib IPI With Food and Drink: You should avoid drinking grapefruit juice while on treatment with Sunitinib IPI.

Pregnancy and Breastfeeding:

- If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

- If you might get pregnant, you should use a reliable method of contraception during treatment with Sunitinib IPI.

- If you are breastfeeding, tell your doctor. You should not breastfeed during treatment with Sunitinib IPI.

Driving and Using Machines: If you experience dizziness or you feel unusually tired, take special care when driving or using machines.

Sunitinib IPI Contains Sodium.

4. Warnings and Precautions:

Talk to your doctor before taking Sunitinib IPI:

- If you have high blood pressure. Sunitinib IPI can raise blood pressure.

- If you have or have had a blood disease, bleeding problems, or bruising. Treatment with Sunitinib IPI may lead to a higher risk of bleeding or changes in the number of certain cells in the blood which may lead to anaemia or affect the ability of your blood to clot. If you are taking warfarin or acenocoumarol, medicines which thin the blood to prevent blood clots, there may be a greater risk of bleeding. Tell your doctor if you have any bleeding while on treatment with Sunitinib IPI.

- If you have heart problems. Sunitinib IPI can cause heart problems. Tell your doctor if you feel very tired, are short of breath, or have swollen feet and ankles.

- If you have abnormal heart rhythm changes. Sunitinib IPI can cause abnormality in your heart rhythm. Your doctor may obtain electrocardiograms to evaluate for these problems during your treatment with Sunitinib IPI. Tell your doctor if you feel dizzy, faint, or have abnormal heartbeats while taking Sunitinib IPI.

- If you have had a recent problem with blood clots in your veins and/or arteries, including stroke, heart attack, embolism, or thrombosis. Call your doctor immediately if you get symptoms such as chest pain or pressure, pain in your arms, back, neck or jaw, shortness of breath, numbness, or weakness on one side of your body, trouble talking, headache, or dizziness while on treatment with Sunitinib IPI.

- If you have or have had an aneurysm or a tear in a blood vessel wall.

- If you have or have had damage to the smallest blood vessels known as thrombotic microangiopathy (TMA). Tell your doctor if you develop fever, fatigue, tiredness, bruising, bleeding, swelling, confusion, vision loss, and seizures.

- If you have thyroid gland problems. Sunitinib IPI can cause thyroid gland problems. Tell your doctor if you get tired more easily, generally feel colder than other people, or your voice deepens whilst taking Sunitinib IPI. Your thyroid function should be checked before you take Sunitinib IPI and regularly while you are taking it. If your thyroid gland is not producing enough thyroid hormone, you may be treated with thyroid hormone replacement.

- If you have or have had pancreatic or gallbladder disorders. Tell your doctor if you develop any of the following signs and symptoms: pain in the stomach (upper abdomen), nausea, vomiting, and fever. These may be caused by inflammation of the pancreas or gallbladder.

- If you have or have had liver problems. Tell your doctor if you develop any of the following signs and symptoms of liver problems during Sunitinib IPI treatment: itching, yellow eyes or skin, dark urine, and pain or discomfort in the right upper stomach area. Your doctor should do blood tests to check your liver function before and during treatment with Sunitinib IPI, and as clinically indicated.

- If you have or have had kidney problems.

- If you are going to have surgery or if you had an operation recently. Sunitinib IPI may affect the way your wounds heal. You will usually be taken off sunitinib IPI if you are having an operation. Your doctor will decide when to start taking Sunitinib IPI again.

- You may be advised to have a dental check-up before you start treatment with Sunitinib IPI.

- If you have or have had pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness, or a feeling of heaviness in the jaw, or loosening of a tooth, tell your doctor and dentist immediately.

- If you need to undergo an invasive dental treatment or dental surgery, tell your doctor that you are being treated with Sunitinib IPI in particular when you are receiving or have received intravenous bisphosphonates.

- If you have or have had skin and subcutaneous tissue disorders. While you are on this medicine “pyoderma gangrenosum” (painful skin ulceration) or “necrotising fasciitis” (rapidly spreading infection of the skin/soft tissue that may be life-threatening) may occur. Contact your doctor immediately if symptoms of infection occur around a skin injury, including fever, pain, redness, swelling, or drainage of pus or blood. This event is generally reversible after Sunitinib IPI discontinuation. Severe skin rashes (StevensJohnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been reported with the use of Sunitinib, appearing initially as reddish targetlike spots or circular patches often with central blisters in the trunk. The rash may progress to widespread blistering or peeling of the skin and may be lifethreatening. If you develop a rash or these skin symptoms, seek immediate advice from a doctor.

- If you have or have had seizures. Notify your doctor as soon as possible if you have high blood pressure, headache, or loss of sight.

- If you have diabetes. Blood sugar levels in diabetic patients should be checked regularly to assess if antidiabetic medicine’s dosage needs to be adjusted to minimise the risk of low blood sugar. Notify your doctor as soon as possible if you experience any signs and symptoms of low blood sugar (fatigue, palpitations, sweating, hunger, and loss of consciousness).

5. How and When to Take Sunitinib IPI:

Always take this medicine exactly as your doctor has told you.

Your doctor will prescribe a dose that is right for you, depending on the type of cancer to be treated. If you are being treated for:

- GIST or MRCC: The usual dose is 50mg once daily for 28 days (4 weeks, followed by 14 days (2 weeks) of rest (no medicine), in 6-week cycles.

- pNET: The usual dose is 37.5mg once daily without a rest period.

Sunitinib IPI can be taken with or without food.

If you have accidentally taken too many capsules, talk to your doctor straight away. You may require medical attention.

If you forget to take Sunitinib IPI. Do not take a double dose to make up for a forgotten dose.

6. Possible Side Effects:

You must immediately contact your doctor if you experience any of those serious side effects:

- Heart problems. Tell your doctor if you feel very tired, are short of breath, or have swollen feet and ankles.

- Lung or breathing problems. Tell your doctor if you develop a cough, chest pain, sudden onset of shortness of breath, or coughing up blood. These may be symptoms of a condition called pulmonary embolism that occurs when blood clots travel to your lungs.

- Kidney disorders. Tell your doctor if you experience altered frequency or absence of urination which may be symptoms of kidney failure.

- Bleeding. Tell your doctor if you have any of these symptoms or a serious bleeding problem during treatment with Sunitinib IPI: painful swollen stomach (abdomen), vomiting blood, black sticky stools, bloody urine, headache or change in your mental status, coughing up of blood, or bloody sputum from the lungs or airway.

- Tumour destruction leading to a hole in the intestine. Tell your doctor if you have severe abdominal pain, fever, nausea, vomiting, blood in your stool, or changes in bowel habits.

Other Side Effects of Sunitinib IPI May Include: Very common (may affect more than 1 in 10 people):

- Reduction in the number of platelets, red blood cells, and/or white blood cells.

- Shortness of breath.

- High blood pressure.

- Extreme tiredness, and loss of strength.

- Swelling caused by fluid under the skin and around the eye, deep allergic rash.

- Mouth pain and irritation, mouth sores/inflammation/dryness, taste disturbances, upset stomach, nausea, vomiting, diarrhoea, constipation, abdominal pain and swelling, and loss and decrease of appetite.

- Decreased activity of the thyroid gland (hypothyroidism).

- Dizziness.

- Headache.

- Nose bleeding.

- Back pain and joint pain.

- Pain in arms and legs.

- Yellow skin, skin discolouration, excess pigmentation of the skin, hair colour change, rash on the palms of the hands and soles of the feet, rash, and dryness of the skin.

- Cough.

- Fever.

- Difficulty in falling asleep.

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

- Blood clots in the blood vessels.

- Deficiency of blood supply to the heart muscle, due to obstruction or constriction of the coronary arteries.

- Chest pain.

- Decrease in the amount of blood pumped by the heart.

- Fluid retention including around the lungs.

- Infections.

- Complication of severe infection that can lead to tissue damage, organ failure, and death.

- Decreased blood sugar level.

- Loss of protein in the urine sometimes resulting in swelling.

- Influenza-like syndrome.

- Abnormal blood tests including pancreatic and liver enzymes.

- High level of uric acid in the blood.

- Haemorrhoids, pain in the rectum, gingival bleeding, difficulty in swallowing, or inability to swallow.

- Burning or painful sensation in the tongue, inflammation of the digestive tract lining, excessive gas in the stomach or intestine.

- Weight loss.

- Musculoskeletal pain, muscular weakness, muscular fatigue, muscle pain, or muscle spasms.

- Nasal dryness or congested nose.

- Excessive tear flow.

- Abnormal sensation of the skin, itching, flaking, and inflammation of the skin, blisters, acne, nail discolouration, or hair loss.

- Abnormal sensations in extremities.

- Abnormally decreased/increased sensitivity, particularly to touch.

- Acid heartburn.

- Dehydration.

- Hot flushes.

- Abnormally coloured urine.

- Depression.

- Chills.

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

- Life-threatening infection of the soft tissue including the anogenital region.

- Stroke.

- Heart attack caused by an interrupted or decreased blood supply to the heart.

- Changes in the electrical activity or abnormal rhythm of the heart.

- Fluid around the heart.

- Liver failure.

- Pain in the stomach (abdomen) caused by inflammation of the pancreas.

- Tumour destruction leading to a hole in the intestine.

- Inflammation of the gallbladder with or without associated gallstones.

- Abnormal tube-like passage from one normal body cavity to another body cavity of the skin.

- Pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness, or a feeling of heaviness in the jaw, or loosening of a tooth.

- Overproduction of thyroid hormones which increases the amount of energy the body uses at rest.

- Problems with wound healing after surgery.

- Increased blood level of an enzyme (creatine phosphokinase) from muscle.

- Excessive reaction to an allergen including hay fever, skin rash, itchy skin, hives, swelling of body parts, and trouble breathing.

- Inflammation of the colon (colitis, colitis ischaemic).

Rare (may affect up to 1 in 1000 people):

- Severe reaction of the skin and/or mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

- Tumour lysis syndrome (TLS) – TLS consists of a group of metabolic complications that can occur during the treatment of cancer. These complications are caused by the break-down products of dying cancer cells and may include the following: nausea, shortness of breath, irregular heartbeat, muscular cramps, seizure, clouding or urine and tiredness associated with abnormal laboratory test results (high potassium, uric acid and phosphorous levels and low calcium levels in the blood) that can lead to changes in kidney function and acute renal failure.

- Abnormal muscle breakdown which can lead to kidney problems (rhabdomyolysis).

- Abnormal changes in the brain that can cause a collection of symptoms including headache, confusion, seizures, and vision loss (reversible posterior leukoencephalopathy syndrome).

- Painful skin ulceration (pyoderma gangrenosum).

- Inflammation of the liver.

- Inflammation of the thyroid gland.

- Damage to the smallest blood vessels known as thrombotic microangiopathy (TMA).

Not known (frequency cannot be estimated from the available data).

- An enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall.