Asikreba

Leaflet accompanying the packaging: patient information

Asikreba, 12.5 mg, hard capsules

Asikreba, 25 mg, hard capsules Asikreba, 37.5 mg, hard capsules

Asikreba, 50 mg, hard capsules

Sunitinib

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for this person. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor. See section 4.

Table of contents of the leaflet

• 1. What is Asikreba and what is it used for
• 2. Important information before taking Asikreba
• 3. How to take Asikreba
• 4. Possible side effects
• 5. How to store Asikreba
• 6. Package contents and other information

1. What is Asikreba and what is it used for

Asikreba contains the active substance sunitinib, which is a protein kinase inhibitor. Asikreba is used to treat cancer. It inhibits the activity of a special group of proteins that are known to participate in the growth and spread of cancer cells.

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

• Gastrointestinal stromal tumors (GIST), a type of stomach and intestine cancer, when imatinib (another anticancer drug) has stopped working or the patient cannot take it;
• Metastatic renal cell carcinoma (MRCC), a type of kidney cancer that has spread to other parts of the body;
• Pancreatic neuroendocrine tumors (pNET), tumors that arise from hormone-producing cells in the pancreas, which are progressing and cannot be surgically removed.

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

2. Important information before taking Asikreba

When not to take Asikreba

• 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 Asikreba, discuss with your doctor:

• If the patient has high blood pressure. Asikreba may increase blood pressure. The doctor may check blood pressure during treatment with Asikreba, and the patient may need to be treated with blood pressure-lowering medications.
• If the patient has or has had blood disorders, bleeding, or thrombocytopenia. Treatment with Asikreba may increase the risk of bleeding or changes in the number of certain blood cells, which can cause anemia or affect the blood's ability to clot. If the patient is taking warfarin or acenocoumarol, blood-thinning medications used to prevent blood clots, there may be a higher risk of bleeding. Tell your doctor about any bleeding during treatment with Asikreba.
• If the patient has heart problems. Asikreba may cause heart problems. Tell your doctor if you experience fatigue, shortness of breath, or swelling of the feet or ankles.
• If the patient has arrhythmias. Asikreba may cause abnormal heart rhythms. During treatment with Asikreba, the doctor may perform an electrocardiogram to assess these disorders. Tell your doctor if you experience dizziness, fainting, or abnormal heart rhythms while taking Asikreba.
• If the patient has recently had blood clots in the veins and/or arteries (including stroke, heart attack, embolism, or thrombosis). Contact your doctor immediately 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.
• If the patient has or has had an aneurysm (enlargement and weakening of the wall of a blood vessel) or a rupture of the blood vessel wall.
• If the patient has or has had damage to the smallest blood vessels (thrombotic microangiopathy). Tell your doctor if you experience fever, fatigue, weakness, bruising, bleeding, swelling, confusion, loss of vision, or seizures.
• If the patient has thyroid problems. Asikreba may cause thyroid problems. Tell your doctor if you experience fatigue, feel colder than others, or have a hoarse voice while taking Asikreba. The doctor should check thyroid function before starting treatment with Asikreba and regularly during treatment. If the thyroid does not produce enough thyroid hormone, the patient may need to be treated with replacement thyroid hormone.
• If the patient has or has had pancreatic or gallbladder problems. Tell your doctor if you experience any of the following symptoms: stomach pain (upper abdomen), nausea, vomiting, and fever. These may be symptoms of pancreatitis or gallbladder inflammation.
• If the patient has liver problems. Inform your doctor if you experience any of the following symptoms of liver disorders: itching, yellowing of the eyes or skin, dark urine, and pain or discomfort in the right upper abdomen. The doctor should order blood tests to check liver function before starting treatment with Asikreba, during treatment, and if there are clinical signs.

and order blood tests to check liver function before starting treatment with Asikreba, during treatment, and if there are clinical signs.

• If the patient has kidney problems. The doctor will monitor kidney function.
• If the patient is to undergo surgery or has recently undergone surgery. Asikreba may affect wound healing. The medicine is usually discontinued in patients before surgery. The doctor will decide when to restart Asikreba.
• A dental examination is recommended before starting treatment with Asikreba:
• if you experience pain in the mouth, toothache, and/or jaw pain, swelling, or ulceration of the mouth, numbness, or a feeling of heaviness in the jaw, or tooth mobility, inform your oncologist and dentist immediately.
• if you need invasive dental treatment or oral surgery, inform your dentist about taking Asikreba, especially if you are also taking or have taken intravenous bisphosphonates. Bisphosphonates are medications used to prevent bone problems that may have been taken for another condition.
• If the patient has or has had skin and subcutaneous tissue disorders. During treatment with this medicine, pyoderma gangrenosum (painful skin ulcers) or necrotizing fasciitis (a rapidly spreading infection of the skin and/or soft tissues that can be life-threatening) may occur. Contact your doctor immediately if you experience symptoms of infection around skin damage, including fever, pain, redness, swelling, or discharge of pus or blood. These disorders usually resolve after discontinuation of Asikreba. During treatment with this medicine, severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been observed, which initially appear as reddened patches with a target-like shape or round patches, often with centrally located blisters. The rash can transform into extensive blisters or skin peeling and can be life-threatening. If you experience a rash or the above-mentioned skin symptoms, contact your doctor immediately.
• If the patient has or has had seizures. Inform your doctor as soon as possible if you experience high blood pressure, headache, or vision loss.
• If the patient has diabetes. In patients with diabetes, blood sugar levels should be regularly checked to assess whether it is necessary to adjust the dose of the antidiabetic medication to minimize the risk of hypoglycemia. Inform your doctor immediately if you experience symptoms of hypoglycemia (fatigue, palpitations, excessive sweating, hunger, and loss of consciousness).

Children and adolescents

Asikreba should not be used in children and adolescents under 18 years of age.

Asikreba and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take, including those obtained without a prescription.

Some medicines may affect the level of Asikreba in your body. Inform your doctor if you are taking medicines containing the following active substances:

• ketokonazole, itraconazole - used to treat fungal infections,
• erythromycin, clarithromycin, rifampicin - used to treat infections,
• ritonavir - used to treat HIV infections,
• dexamethasone - a corticosteroid used in various diseases (such as allergic disorders and/or respiratory disorders or skin diseases),
• phenytoin, carbamazepine, phenobarbital - used to treat epilepsy and other neurological conditions,
• products containing St. John's wort (Hypericum perforatum) - used to treat depression and anxiety disorders.

Taking Asikreba with food and drink

Do not drink grapefruit juice while taking Asikreba.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor or pharmacist before taking this medicine.

Women who may become pregnant should use effective contraception during treatment with Asikreba.

Breastfeeding women should inform their doctor. Do not breastfeed while taking Asikreba.

Driving and using machines

If you experience dizziness or significant fatigue, be careful when driving or operating machinery.

Asikreba contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per capsule, which means it is considered "sodium-free".

Asikreba 37.5 mg contains orange yellow FCF (E110) and tartrazine

Asikreba 37.5 mg hard capsules contain orange yellow FCF (E110) and tartrazine (E102), which may cause an allergic reaction.

3. How to take Asikreba

Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor.

The doctor will prescribe the dose suitable for you, depending on the type of cancer.

For patients treated for GIST or MRCC, the usual dose is 50 mg taken once a day for 28 days (4 weeks), followed by a 14-day (2-week) break (without the medicine), in 6-week treatment cycles.

For patients treated for pNET, the usual dose is 37.5 mg taken once a day continuously.

The doctor will determine the appropriate dose for you and decide when to stop treatment with Asikreba.

Asikreba can be taken with or without food.

Taking a higher dose of Asikreba than recommended

If you have taken a higher dose than recommended, contact your doctor immediately. Treatment may be necessary.

Missing a dose of Asikreba

Do not take a double dose to make up for a missed dose.

4. Possible side effects

Like all medicines, Asikreba can cause side effects, although not everybody gets them.

Contact your doctor immediately if you experience any of the following serious side effects (see also Important information before taking Asikreba):

Heart problems. Tell your doctor if you feel very tired, have shortness of breath, or swelling of the feet and ankles. These may be symptoms of heart problems, including heart failure and heart muscle disorders (cardiomyopathy).

Lung problems or breathing difficulties. Tell your doctor if you experience coughing, 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 move to the lungs.

Kidney problems. Tell your doctor if you experience changes in urination frequency or inability to urinate, which may be a sign of kidney failure.

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

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

Other side effects of Asikreba may include:

Very common: may affect more than 1 in 10 people

• Decreased platelet count, red blood cells, and/or white blood cells (e.g., neutrophils).
• Shortness of breath.
• High blood pressure.
• Extreme fatigue, weakness.
• Swelling caused by fluid accumulation under the skin and around the eyes, allergic rash, deep.
• Pain and/or irritation in the mouth, painful ulcers, and/or inflammation, and/or dryness of the mouth, taste disorders, stomach disorders, nausea, vomiting, diarrhea, constipation, abdominal pain and/or swelling, loss of appetite.
• Decreased thyroid activity (hypothyroidism).
• Dizziness.
• Headache.
• Nosebleeds.
• Back pain, joint pain.
• Arm and leg pain.
• Yellowing of the skin and/or discoloration, excessive pigmentation of the skin, hair color changes, palmar-plantar erythrodysesthesia, rash, dry skin.
• Cough.
• Fever.
• Sleep disorders .

Common: may affect up to 1 in 10 people

• Blood clots in blood vessels.
• Insufficient blood supply to the heart due to a blockage or narrowing of the coronary arteries.
• Chest pain.
• Decreased amount of blood pumped by the heart.
• Fluid accumulation, including in the lungs.
• Infections.
• A severe infection complication (sepsis) that can lead to tissue damage, organ failure, and death.
• Low blood sugar levels (see section 2).
• Protein loss in urine, sometimes causing swelling.
• Flu-like symptoms.
• Abnormal blood test results, including pancreatic and liver enzymes.
• High uric acid levels in the blood.
• Hemorrhoids, anal pain, gum bleeding, difficulty swallowing, or loss of swallowing ability.
• Burning or pain in the tongue, inflammation of the mucous membrane of the digestive tract, excessive gas in the stomach or intestines.
• Weight loss.
• Musculoskeletal pain (muscle and bone pain), muscle weakness, muscle fatigue, muscle cramps.
• Dryness of the nasal mucosa, nasal congestion, excessive tearing.
• Skin sensitivity disorders, itching, peeling, and inflammation, blisters, acne, nail discoloration, hair loss.
• Skin sensation disorders.
• Sensitivity disorders, especially to touch.
• Heartburn.
• Dehydration.
• Hot flashes.
• Abnormal urine color.
• Depression.
• Chills.

Uncommon: may affect up to 1 in 100 people

• Life-threatening infection of soft tissues, including the perianal area (see section 2).
• Stroke.
• Heart attack caused by interruption or reduction of blood supply to the heart.
• Changes in heart electrical activity or rhythm disorders.
• Fluid accumulation around the heart (pericardial effusion).
• Liver failure.
• Stomach pain (abdominal pain) caused by pancreatitis.
• Tumor lysis syndrome leading to intestinal perforation (perforation).
• Inflammation (swelling or redness) of the gallbladder with or without gallstones.
• Formation of abnormal connections between one body cavity and another or with the skin.
• Mouth pain, toothache, and/or jaw pain, swelling, or ulceration of the mouth, numbness, or a feeling of heaviness in the jaw, or tooth mobility. These may be symptoms of jawbone damage (osteonecrosis), see section 2.
• Excessive production of thyroid hormones leading to increased resting metabolism.
• Impaired wound healing after surgery.
• Increased activity of the muscle enzyme (creatine phosphokinase) in the blood.
• Excessive allergic reaction, including fever, skin rash, itching, hives, swelling of body parts, and breathing difficulties.
• Inflammation of the large intestine, ischemic inflammation of the large intestine.

Rare: may affect up to 1 in 1000 people

• Severe skin and/or mucous membrane reaction (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).
• Tumor lysis syndrome, which is a group of metabolic complications that can occur during cancer treatment. These complications are caused by the breakdown products of dying cancer cells and can include nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, lack of urine clarity, and fatigue associated with abnormal laboratory test results (high potassium, uric acid, and phosphorus levels and low calcium levels in the blood), which can lead to kidney changes and acute kidney failure.
• Abnormal muscle breakdown, which can cause kidney disease (rhabdomyolysis).
• Abnormal brain changes, which can cause a syndrome of symptoms including headache, disorientation, seizures, and vision loss (reversible posterior leukoencephalopathy syndrome).
• Painful skin ulcers (pyoderma gangrenosum).
• Hepatitis.
• Thyroid inflammation.
• Damaged smallest blood vessels (thrombotic microangiopathy).

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

• Enlargement and weakening of the blood vessel wall or rupture of the blood vessel wall (aneurysm and arterial dissection).

Reporting side effects

If you experience any side effects, including any side effects not listed in the leaflet, tell your doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring 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.

Side effects can also be reported to the marketing authorization holder.

Reporting side effects will help gather more information on the safety of this medicine.

5. How to store Asikreba

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

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

There are no special precautions for storing the medicine.

Do not use this medicine if the packaging is damaged or shows signs of tampering.

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. Package contents and other information

What Asikreba contains

• The active substance of Asikreba is sunitinib. Asikreba, 12.5 mg, hard capsules: one capsule contains sunitinib malate, equivalent to 12.5 mg of sunitinib. Asikreba 25 mg, hard capsules: one capsule contains sunitinib malate, equivalent to 25 mg of sunitinib. Asikreba 37.5 mg, hard capsules: one capsule contains sunitinib malate, equivalent to 37.5 mg of sunitinib. Asikreba 50 mg, hard capsules: one capsule contains sunitinib malate, equivalent to 50 mg of sunitinib.
• Other ingredients are: Asikreba, 12.5 mg, hard capsules The capsule contents are: povidone K25, mannitol, sodium croscarmellose, magnesium stearate The capsule shell is: gelatin, iron oxide red (E172), titanium dioxide (E171), iron oxide black (E172) The printing ink is: shellac, propylene glycol, sodium hydroxide, povidone, titanium dioxide (E171).

Asikreba, 25 mg, hard capsules The capsule contents are: povidone K25, mannitol, sodium croscarmellose, magnesium stearate The capsule shell is: gelatin, titanium dioxide (E171), iron oxide red (E172), iron oxide black (E172), iron oxide yellow (E172) The printing ink is: shellac, propylene glycol, sodium hydroxide, povidone, titanium dioxide (E171).

Asikreba, 37.5 mg, hard capsules The capsule contents are: povidone K25, mannitol, sodium croscarmellose, magnesium stearate The capsule shell is: gelatin, orange yellow FCF (E110), tartrazine (E102), titanium dioxide (E171) The printing ink is: shellac, propylene glycol, ammonium hydroxide, iron oxide black (E172), potassium hydroxide.

Asikreba, 50 mg, hard capsules The capsule contents are: povidone K25, mannitol (E421), sodium croscarmellose, magnesium stearate The capsule shell is: gelatin, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172), iron oxide black (E172) The printing ink is: shellac, propylene glycol, sodium hydroxide, povidone, titanium dioxide (E171).

What Asikreba looks like and contents of the pack

Asikreba, 12.5 mg, hard capsules Hard capsules with dark brown, opaque cap and dark brown, opaque body, 13.8-14.8 mm, with white ink printing "LP" on the cap and "650" on the body, containing yellow to orange granular powder.

Asikreba, 25 mg, hard capsules Hard capsules with light brown, opaque cap and dark brown, opaque body, 15.4-16.4 mm, with white ink printing "LP" on the cap and "651" on the body, containing yellow to orange granular powder.

Asikreba, 37.5 mg, hard capsules Hard capsules with yellow, opaque cap and yellow, opaque body, 17.5-18.5 mm, with black ink printing "LP" on the cap and "652" on the body, containing yellow to orange granular powder.

• Asikreba, 50 mg, hard capsules Hard capsules with light brown, opaque cap and light brown, opaque body, 17.5-18.5 mm, with white ink printing "LP" on the cap and "653" on the body, containing yellow to orange granular powder.

Asikreba hard capsules are packaged in a bottle containing 30 hard capsules and a cardboard box with blisters of 28 or 30 hard capsules.

Marketing authorization holder

Zentiva k.s. U Kabelovny 130 Dolni Měcholupy 102 37 Prague 10 Czech Republic

Manufacturer/Importer

Pharmadox Healthcare Ltd. KW20A Kordin Industrial Park Paola PLA 3000 Malta Alvogen Malta (Out-Licensing) Ltd. Malta Life Sciences Park, Building 1, Level 4 Sir Temi Zammit Buildings San Ġwann SĠN 3000 Malta

For more information about this medicine, contact:

Zentiva Polska Sp. z o.o. ul. Bonifraterska 17 00-203 Warsaw tel: +48 22 375 92 00 (logo of the marketing authorization holder)

Date of last revision of the leaflet: