Klertis

Package leaflet: Information for the patient

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

• 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:

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 sunitinib as the active substance, a protein kinase inhibitor. This medicine is used in cancer treatment, as it inhibits the activity of a specific group of proteins involved in the growth and spread of cancer cells.

Klertis is used in adult patients for the treatment of the following tumours:

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

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

2. Important information before using Klertis

When not to use Klertis

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

Warnings and precautions
Before taking Klertis, discuss with your doctor if:

• the patient has high blood pressure. Klertis may increase blood pressure. Your doctor may monitor your blood pressure during treatment with Klertis and, if necessary, prescribe antihypertensive medications.
• the patient has or has had blood disorders, bleeding problems or bruising. Treatment with Klertis may increase the risk of bleeding or alter the number of certain blood cells, leading to anaemia or clotting disorders. If the patient is taking warfarin or acenocoumarol (medicines that thin the blood to prevent clots), the risk of bleeding is higher. If any bleeding occurs during treatment with Klertis, inform your doctor immediately.
• the patient has heart disease. Klertis may cause heart-related conditions. If the patient experiences severe fatigue, shortness of breath, or swelling in the feet and ankles, inform the doctor.
• the patient has heart rhythm disorders. Klertis may cause heart rhythm disturbances. Your doctor may recommend an electrocardiogram (ECG) during treatment to monitor these conditions. Seek medical advice promptly if you experience dizziness, fainting, or irregular heartbeat.
• the patient has recently had problems with blood clots in veins and/or arteries (types of blood vessels), including stroke, heart attack, embolism, or thrombosis. If such symptoms occur during treatment with Klertis—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—seek immediate medical attention.
• the patient has or has had an aneurysm (a weakened and enlarged blood vessel wall) or a tear in the blood vessel wall.
• the patient currently has or has previously had damage to the smallest blood vessels, known as thrombotic microangiopathy (TMA). If fever, fatigue, exhaustion, bruising, bleeding, swelling, confusion, vision loss, or seizures occur, consult a doctor immediately.
• the patient has thyroid function disorders. Klertis may affect thyroid function. If, during treatment with Klertis, the patient becomes easily fatigued, feels unusually cold, or develops a deeper voice, inform the doctor. Thyroid function should be checked before starting Klertis and monitored regularly during treatment. Patients whose thyroid does not produce sufficient hormones may require hormone replacement therapy.
• the patient has or has had pancreatic or gallbladder disorders. Consult a doctor if the patient experiences any of the following symptoms: stomach pain (epigastric pain), nausea, vomiting, or fever. These may indicate pancreatitis or cholecystitis.
• the patient has or has had liver function disorders. Inform the doctor if any of the following signs of liver problems occur during treatment with Klertis: itching, yellowing of the eyes or skin, dark urine, or pain/discomfort in the upper right abdomen. Your doctor will order blood tests to monitor liver function before and during treatment, and whenever clinically indicated.
• the patient has or has had kidney function disorders. Your doctor will monitor kidney function.
• the patient is scheduled for surgery or has recently undergone surgery. Klertis may affect wound healing. If surgery is planned, your doctor will usually advise stopping this medicine and will specify when to resume treatment.
• before starting Klertis, your doctor may recommend a dental check-up.
• If the patient experiences or has experienced mouth pain, tooth, jaw, and/or mandible pain, swelling or ulceration in the mouth, numbness or heaviness in the jaw and/or mandible, or loose teeth, inform the treating doctor and dentist immediately.
• If the patient requires invasive dental treatment or procedure, inform the dentist about taking Klertis, especially if the patient is currently or has previously received intravenous bisphosphonates (medicines used to prevent bone complications and treat other conditions).
• the patient has or has had skin and subcutaneous tissue disorders. During treatment with Klertis, conditions such as "pyoderma gangrenosum" (painful skin ulceration) or "necrotizing fasciitis" (rapidly spreading infection of subcutaneous tissue that may be life-threatening) may occur. Seek immediate medical attention if signs of wound infection appear, including fever, pain, redness, swelling, or discharge of pus or blood. These effects usually resolve after discontinuation of sunitinib. Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been reported during sunitinib treatment, initially presenting as red, target-like or circular rashes on the trunk, often with central blisters. The rash may progress to widespread blistering or skin peeling, which may be life-threatening. If a rash or any of these skin symptoms occur, seek immediate medical advice.
• the patient has or has had seizures. If high blood pressure, headache, or vision loss occurs, inform the doctor as soon as possible.
• the patient has diabetes. Blood glucose levels should be monitored regularly in diabetic patients to determine whether an adjustment in antidiabetic medication dosage is needed to reduce the risk of hypoglycaemia. If any symptoms of low blood sugar occur (fatigue, palpitations, sweating, hunger, loss of consciousness), seek medical advice immediately.

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

Klertis with other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines planned for future use.
Some medicines may affect the concentration of Klertis in the body. If the patient is taking medicines containing any of the following active substances, inform the doctor:

• ketoconazole, itraconazole (medicines used to treat fungal infections)
• erythromycin, clarithromycin, rifampicin (medicines used to treat infections)
• ritonavir (a medicine used to treat HIV infection)
• dexamethasone (a corticosteroid used to treat various conditions such as allergies, respiratory disorders, or skin diseases)
• phenytoin, carbamazepine, phenobarbital (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 the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor or pharmacist before using this medicine.
Women of childbearing potential should use effective contraception during treatment with Klertis.
If the patient is breastfeeding, inform the doctor. Breastfeeding must not be continued during treatment with Klertis.

Driving and operating machinery
Patients who experience dizziness or unusual fatigue should exercise particular caution when driving or operating machinery.

Klertis contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, meaning the medicine is considered "sodium-free".

3. How to use Klertis
Always use this medicine exactly as prescribed by your doctor. If in doubt, consult your doctor.
Your doctor will prescribe the appropriate dose of the medicine depending on the type of tumour.

• 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) treatment-free interval. This forms a 6-week cycle;
• pancreatic neuroendocrine tumour (pNET): the recommended dose is 37.5 mg once daily without a treatment break.

Your doctor will determine the appropriate dose for the patient and will advise whether and when to interrupt treatment with Klertis.
Klertis may be taken with or without food.

Accidental overdose of Klertis
If the patient accidentally takes more capsules than recommended, seek immediate medical advice. Medical assistance may be required.

Missed dose of Klertis
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.
If the patient experiences any of the following serious adverse reactions, contact a doctor immediately (see also section "Important information before using Klertis").

Heart problems. Tell the doctor if the patient experiences significant fatigue, shortness of breath, or swelling of the feet and ankles. These may be symptoms of heart-related disorders, including heart failure and heart muscle disease (cardiomyopathy).

Lung problems or breathing difficulties. Tell the doctor if the patient develops cough, chest pain, sudden shortness of breath, or coughs 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 of urination or stops urinating altogether, as these may be symptoms of kidney failure.

Bleeding. Tell the doctor if any of the following symptoms occur during treatment with Klertis, or if severe bleeding occurs: 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 rupture 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 habits.

Other adverse reactions during treatment with Klertis may include:

Very common (may affect more than 1 in 10 people):

• Decreased 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, allergic rash
• Pain and/or irritation of the mouth, mouth ulcers, inflammation, dryness of the oral mucosa, taste disturbances, indigestion, nausea, vomiting, diarrhoea, constipation, abdominal pain and/or swelling, loss of appetite or reduced appetite
• Decreased thyroid function (hypothyroidism)
• Dizziness
• Headache
• Nosebleeds
• Back pain, joint pain
• Pain in hands and feet
• Yellowing and/or discolouration of the skin, 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 clot formation in blood vessels
• Reduced 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 (blood infection), which may lead to tissue damage, organ failure, and death
• Low blood sugar levels (see section 2)
• Protein loss in urine, sometimes leading to oedema
• Flu-like symptoms
• 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 inability to swallow
• Burning sensation or pain in the tongue, inflammation of the gastrointestinal mucosa, excessive gas in the stomach or intestines
• Weight loss
• Muscle and bone pain, muscle weakness, muscle fatigue, muscle pain, muscle cramps
• Dry nose, nasal mucosa congestion
• Excessive tearing
• Abnormal skin sensations, itching, skin peeling and inflammation, blister formation, acne, nail discolouration, hair loss
• Unusual sensations in the limbs
• Abnormal decreased or increased 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 in the genital and anal areas (see section 2)
• Stroke
• Myocardial infarction due to interrupted or reduced blood supply to the heart
• Changes in the heart's electrical function or irregular heartbeat
• Fluid around the heart (pericardial effusion)
• Liver failure
• Abdominal pain due to pancreatitis
• Tumour rupture leading to intestinal perforation
• Inflammation (swelling and redness) of the gallbladder with or without gallstones
• Formation of an abnormal connection between one body cavity and another or with the skin (fistula)
• Mouth pain, tooth and/or jaw pain, swelling or ulceration in the mouth, numbness or heaviness in the jaw, loose teeth. These may be symptoms of damage (necrosis) of the jawbone and/or mandible (see section 2)
• Excessive production of thyroid hormones, leading to increased energy consumption by the body (increased metabolism) at rest
• Impaired postoperative wound healing
• Increased activity of creatine kinase enzyme of muscle origin
• Excessive allergic reaction, including hay fever, skin rash, skin itching, urticaria, swelling of certain body parts, and breathing difficulties
• Colitis (inflammation of the colon, ischemic 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 anticancer treatment. These complications are caused by the breakdown products of cancer cells and may include: nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, and fatigue combined with abnormal laboratory results (high levels of potassium, uric acid, and phosphate, and low calcium levels in the blood), which may indicate kidney dysfunction and acute kidney failure
• Abnormal muscle breakdown, which may cause kidney problems (rhabdomyolysis)
• Abnormal changes in the brain that may cause various symptoms, including headache, confusion, seizures, and vision loss (reversible posterior leukoencephalopathy syndrome)
• Painful skin ulcers (pyoderma gangrenosum)
• Hepatitis (liver inflammation)
• Thyroiditis (thyroid inflammation)
• Damage to the smallest blood vessels (thrombotic microangiopathy)

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

• Enlargement or weakening of the aortic wall (aortic aneurysm or 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 reactions occur, including any not listed in this leaflet, tell a doctor, pharmacist, or nurse. Adverse reactions can also be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 Klertis
Keep the 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 stated month.
No special storage conditions apply.
Medicines must not be disposed of via wastewater or household waste. Ask a 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 succinate equivalent to
12.5 mg, 25 mg or 50 mg of sunitinib.
The other ingredients are mannitol, sodium croscarmellose, 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, self-sealing Coni-Snap type capsule, unmarked, size “3”, with an opaque, medium orange cap and an opaque, bright yellow body, filled with orange granules.
Klertis 25 mg: hard, gelatin, self-sealing Coni-Snap type capsule, unmarked, size “2”, with an opaque, medium orange cap and an olive-green body, filled with orange granules.
Klertis 50 mg: hard, gelatin, self-sealing Coni-Snap type capsule, unmarked, 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 cardboard box or 30 capsules in an HDPE bottle with a PP child-resistant cap, in a cardboard box.

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 capsule, hard
Bulgaria: Klertis 12.5 mg, 25 mg, 50 mg твърда капсула
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