KLERTIS 25 mg Capsules

Contents of the leaflet

1. Package Leaflet: Information for the Patient
   1. Klertis, 25 mg, hard capsules
   2. Klertis, 50 mg, hard capsules
   3. It is very important that you read the contents of this leaflet carefully before taking this medicine, as it contains important information for you.
   4. Contents of the pack:
2. What Klertis is and what it is used for
3. Important information before taking Klertis
   1. When not to take Klertis
   2. Warnings and precautions
   3. Children and adolescents
   4. Klertis and other medicines
   5. Klertis with food and drink
   6. Pregnancy and breastfeeding
   7. Driving and using machines
   8. Klertis contains sodium
4. How to take Klertis
   1. If you take more Klertis than you should
   2. If you forget to take Klertis
5. Possible side effects
   1. Reporting of side effects
6. How to store Klertis
7. Contents of the pack and other information
   1. What Klertis contains
   2. What Klertis looks like and contents of the pack
   3. Marketing authorisation holder
   4. Manufacturer
   5. This medicinal product is authorised in the Member States of the European Economic Area under the following names:
   6. Date of last revision of the leaflet: 14.05.2024

Package Leaflet: Information for the Patient

Klertis, 12.5 mg, hard capsules

Klertis, 25 mg, hard capsules

Klertis, 50 mg, hard capsules

Sunitinib

It is very important that you read the contents of this leaflet carefully before taking this medicine, as it contains important information for you.

• You should 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. 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, please inform your doctor or pharmacist. See section 4.

Contents of the pack:

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

1. What Klertis is and what it is used for

Klertis hard capsules contain the active substance sunitinib, a protein kinase inhibitor. Klertis is used to treat cancer, as it inhibits the activity of a specific group of proteins involved in the growth and spread of cancer cells.

Klertis is used in adults to treat the following types of cancer:

• gastrointestinal stromal tumour (GIST), a type of stomach and intestine cancer, when imatinib (another anti-cancer medicine) is not 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), cancers of the hormone-producing cells in the pancreas that are advanced or cannot be surgically removed.

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

2. Important information before taking Klertis

When not to take Klertis

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

Warnings and precautions

Before taking Klertis, tell your doctor if:

• you have high blood pressure. Klertis may increase your blood pressure. Your doctor may monitor your blood pressure and treat it if necessary.
• you have or have had bleeding problems or blood clotting disorders. Taking Klertis may increase the risk of bleeding or change the number of certain blood cells, leading to anaemia or blood clotting disorders. If you are taking warfarin or acenocoumarol (blood thinners), the risk of bleeding is higher. If you experience any bleeding while taking Klertis, tell your doctor.
• you have heart problems. Klertis may cause heart problems. If you experience severe fatigue, shortness of breath, or swelling of your feet and ankles, tell your doctor.
• you have irregular heartbeats. Klertis may cause irregular heartbeats. Your doctor may perform an electrocardiogram (ECG) to monitor these irregularities. If you experience dizziness, fainting, or abnormal heart rhythms, tell your doctor.
• you have recently had problems with blood clots in your veins and/or arteries (types of blood vessels), including stroke, heart attack, pulmonary embolism, or deep vein thrombosis. 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, tell your doctor immediately.
• you have or have had an aneurysm (enlargement and weakening of the wall of a blood vessel) or a tear in the wall of a blood vessel.
• you currently have or have had microangiopathic haemolytic anaemia (TMA), a condition where small blood vessels are damaged. If you experience fever, fatigue, bruising, bleeding, swelling, confusion, loss of vision, or seizures, tell your doctor.
• you have thyroid problems. Klertis may cause thyroid problems. If you experience fatigue, cold intolerance, or changes in your voice, tell your doctor. Your thyroid function should be checked before starting Klertis and regularly during treatment. Patients with underactive thyroid may need to take replacement hormones.
• you have or have had pancreas or gallbladder problems. Tell your doctor if you experience symptoms such as stomach pain, nausea, vomiting, or fever, which may be signs of pancreatitis or gallbladder inflammation.
• you have or have had liver problems. Tell your doctor if you experience symptoms such as itching, yellowing of the eyes or skin, dark urine, or pain or discomfort in the upper right side of the abdomen, which may be signs of liver problems. Your doctor may perform blood tests to check your liver function before and during treatment with Klertis.
• you have or have had kidney problems. Your doctor will monitor your kidney function.
• you are going to have surgery or have recently had surgery. Klertis may affect wound healing. If you are going to have surgery, your doctor may advise you to stop taking Klertis and will tell you when to restart it.
• before starting Klertis, your doctor may recommend a dental check-up.
• If you experience toothache, jaw pain, or swelling, tell your doctor and dentist immediately.
• If you need to undergo invasive dental treatment or surgery, tell your dentist that you are taking Klertis, especially if you are also taking or have taken bisphosphonates (medicines used to prevent bone complications and treat other conditions) intravenously.
• you have or have had skin and subcutaneous tissue disorders. During treatment with Klertis, you may experience "pyoderma gangrenosum" (painful skin ulcers) or "necrotizing fasciitis" (a life-threatening infection of the tissue under the skin). If you experience symptoms of wound infection, such as fever, pain, redness, swelling, or discharge, tell your doctor immediately. This condition usually resolves after stopping sunitinib. During treatment with sunitinib, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been reported, initially appearing as red patches resembling target lesions or circular patches on the trunk, often with central blisters. The rash may progress to widespread blisters or skin peeling, which can be life-threatening. If you experience a rash or these skin symptoms, tell your doctor immediately.
• you have or have had seizures. If you experience high blood pressure, headache, or vision loss, tell your doctor as soon as possible.
• you have diabetes. If you experience symptoms of low blood sugar, such as fatigue, palpitations, sweating, hunger, or loss of consciousness, tell your doctor immediately.

Children and adolescents

Klertis is not recommended for children and adolescents under 18 years of age.

Klertis and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take.

• ketokonazol, itrakonazol (medicines used to treat fungal infections)
• erytromycyna, klarytromycyna, ryfampicyna (medicines used to treat infections)
• rytonawir (medicine used to treat HIV infection)
• deksametazon (corticosteroid used to treat various conditions, such as allergies, respiratory disorders, or skin diseases)
• fenytoina, karbamazepina, fenobarbital (medicines used to treat epilepsy and other neurological disorders)
• herbal medicines containing St. John's Wort (Hypericum perforatum), used to treat depression and anxiety

Klertis with food and drink

Do not drink grapefruit juice while taking Klertis.

Pregnancy and breastfeeding

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

Women of childbearing age should use effective contraception during treatment with Klertis.

If you are breastfeeding, tell your doctor. You should not breastfeed while taking Klertis.

Driving and using machines

Patients who experience dizziness or unusual fatigue should be cautious when driving or operating machinery.

Klertis contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per capsule, which is essentially "sodium-free".

3. How to take Klertis

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

Your doctor will prescribe the dose that is right for you, depending on the type of cancer you have.

• gastrointestinal stromal tumour (GIST) or metastatic renal cell carcinoma (MRCC): the recommended dose is 50 mg taken once daily for 28 days (4 weeks), followed by a 14-day (2-week) break (without taking the medicine), which makes up a 6-week cycle;
• pancreatic neuroendocrine tumours (pNET): the recommended dose is 37.5 mg taken once daily without a break.

Your doctor will determine the dose that is right for you and will tell you if and when you should stop taking Klertis.

You can take Klertis with or without food.

If you take more Klertis than you should

If you accidentally take too many Klertis capsules, tell your doctor immediately. Medical attention may be necessary.

If you forget to take Klertis

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.

If you experience any of the following serious side effects, tell your doctor immediately (see also section 2).

Heart problems. Tell your doctor if you experience severe fatigue, shortness of breath, or swelling of your feet and ankles. These may be signs of heart problems, including heart failure and cardiomyopathy.

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

Kidney problems. Tell your doctor if you experience changes in urination frequency or if you do not urinate, as these may be signs of kidney failure.

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

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

Other side effects that may occur during treatment with Klertis include:

• reduced number of platelets, red blood cells, and/or white blood cells (e.g., neutrophils)
• shortness of breath
• high blood pressure
• extreme fatigue, weakness
• swelling due to fluid accumulation under the skin and around the eyes, allergic rash
• mouth pain and/or irritation, mouth ulcers, inflammation, dryness of the mouth mucosa, taste disturbances, nausea, vomiting, diarrhoea, constipation, stomach pain and/or swelling, loss of appetite
• reduced thyroid function (hypothyroidism)
• dizziness
• headache
• nosebleeds
• back pain, joint pain
• hand and foot pain
• yellowing and/or darkening of the skin, excessive skin pigmentation, hair colour changes, palmar-plantar erythrodysesthesia, rash, dry skin
• cough
• fever
• sleep disturbances

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

• blood clots in blood vessels
• insufficient blood flow to the heart muscle due to blockage or narrowing of the coronary arteries
• chest pain
• reduced amount of blood pumped by the heart
• fluid accumulation, e.g., around the lungs
• infections
• severe infection complication (sepsis), which can lead to tissue damage, organ failure, and death
• low blood sugar (see section 2)
• protein loss in urine, which can sometimes lead to swelling
• flu-like symptoms
• abnormal blood test results, including abnormal liver and pancreatic enzyme activity
• high levels of uric acid in the blood
• haemorrhoids, anal pain, gum bleeding, difficulty swallowing or inability to swallow
• mouth pain, toothache, and/or jaw pain, mouth swelling or ulcers, numbness or heaviness in the jaw, tooth mobility. These may be signs of jawbone damage (osteonecrosis) (see section 2)
• excessive production of thyroid hormones, leading to increased energy expenditure at rest
• wound healing problems after surgery
• increased activity of the muscle enzyme creatine kinase
• allergic reactions, including hay fever, skin rash, itching, hives, swelling of certain parts of the body, and breathing difficulties
• inflammation of the colon (colitis, ischaemic colitis)

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

• life-threatening infection of the soft tissues, including the genital and anal areas
• stroke
• heart attack due to interrupted or reduced blood flow to the heart
• changes in the electrical activity of the heart or abnormal heart rhythm
• fluid accumulation around the heart (pericardial effusion)
• liver failure
• stomach pain due to pancreatitis
• tumour lysis syndrome leading to bowel perforation
• inflammation of the gallbladder (cholecystitis) with or without gallstones
• formation of abnormal connections between one body cavity and another or with the skin (fistula)
• mouth pain, toothache, and/or jaw pain, mouth swelling or ulcers, numbness or heaviness in the jaw, tooth mobility. These may be signs of jawbone damage (osteonecrosis) (see section 2)
• excessive production of thyroid hormones, leading to increased energy expenditure at rest
• wound healing problems after surgery
• increased activity of the muscle enzyme creatine kinase
• allergic reactions, including hay fever, skin rash, itching, hives, swelling of certain parts of the body, and breathing difficulties
• inflammation of the colon (colitis, ischaemic colitis)

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

• severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme)
• tumour lysis syndrome - a group of metabolic complications that can occur during anti-cancer treatment. These complications are caused by the breakdown products of cancer cells and can include nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, clouding of urine, and fatigue, along with abnormal laboratory test results (high levels of potassium, uric acid, and phosphorus, and low levels of calcium in the blood), which can indicate kidney problems and acute kidney failure
• abnormal muscle breakdown, which can cause kidney problems (rhabdomyolysis)
• abnormal changes in the brain, which can cause a range of symptoms, including headache, confusion, seizures, and vision loss (reversible posterior leukoencephalopathy syndrome)
• painful skin ulcers (pyoderma gangrenosum)
• hepatitis
• thyroiditis
• microangiopathic haemolytic anaemia (TMA)

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

• enlargement and weakening of the aorta (aortic aneurysm or aortic dissection)
• lack of energy, confusion, drowsiness, loss of consciousness, or coma - these symptoms may be signs of a toxic effect of high blood ammonia levels on the brain (hyperammonaemic encephalopathy)

Reporting of side effects

If you experience any side effects, including any not listed in this leaflet, please inform your doctor, pharmacist, or nurse. You can also report side effects directly to the national reporting system: Department of Medicines Monitoring, 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. You can also report side effects to the marketing authorisation holder.

5. How to store Klertis

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the blister, bottle, and carton after "EXP" and "Expiry Date (EXP)". The expiry date refers to the last day of the month.

There are no special storage precautions for this medicine.

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

6. Contents of the pack and other information

What Klertis contains

The active substance is sunitinib. Each capsule contains sunitinib malate equivalent to 12.5 mg, 25 mg, or 50 mg of sunitinib.

The other ingredients are mannitol, croscarmellose sodium, povidone K30, and magnesium stearate.

The capsule shell contains:

• Klertis, 12.5 mg, hard capsules: gelatin, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172)
• Klertis, 25 mg, hard capsules: gelatin, titanium dioxide (E171), yellow iron oxide (E172), black iron oxide (E172), red iron oxide (E172)
• Klertis, 50 mg, hard capsules: gelatin, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172). See section 2.

What Klertis looks like and contents of the pack

Klertis, 12.5 mg: hard, gelatin capsule, size "3", with an opaque, medium orange cap and an opaque, intense yellow body, filled with orange granules.

Klertis, 25 mg: hard, gelatin capsule, size "2", with an opaque, medium orange cap and an olive green body, filled with orange granules.

Klertis, 50 mg: hard, gelatin capsule, size "0", with an opaque, medium orange cap and an opaque, medium orange body, filled with orange granules.

28 capsules in PVC/Aclar/Aluminium blisters in a carton or 30 capsules in an HDPE bottle with a PP cap, child-resistant, in a carton.

Marketing authorisation holder

Egis Pharmaceuticals PLC, Keresztúri út 30-38, 1106 Budapest, Hungary

Manufacturer

Egis Pharmaceuticals PLC, Bökényföldi út 118-120, 1165 Budapest, Hungary

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

Netherlands: Klertis 12.5 mg, 25 mg, 50 mg, hard capsules

Bulgaria: Klertis 12.5 mg, 25 mg, 50 mg твърдa капсулa

Czech Republic: Klertis

Hungary: Klertis 12.5 mg, 25 mg, 50 mg kemény kapszula

Lithuania: Klertis 12.5 mg, 25 mg, 50 mg kietosios kapsulės

Latvia: Klertis 12.5 mg, 25 mg, 50 mg cietās kapsulas

Poland: Klertis

Romania: Klertis 12.5 mg, 25 mg, 50 mg, capsule

Slovakia: Klertis 12.5 mg, 25 mg, 50 mg tvrdé kapsuly

Date of last revision of the leaflet: 14.05.2024