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

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. 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. Contents of the packaging 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 works by blocking the activity of a special group of proteins that are involved in the growth and spread of cancer cells.

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

• Gastrointestinal stromal tumor (GIST), a type of stomach and intestine cancer, when imatinib (another anticancer medicine) 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 removed by surgery.

If you have any questions about how Asikreba works or why it has been prescribed, you should 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, you should 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 medicines if necessary.
• If the patient has or has had blood disorders, bleeding, or bruising. 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 medicines used to prevent blood clots, there may be a higher risk of bleeding. The patient should tell their doctor about any bleeding during treatment with Asikreba.
• If the patient has heart problems. Asikreba may cause heart problems. The patient should tell their doctor if they experience extreme 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 arrhythmias. The patient should tell their doctor if they 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). The patient should contact their doctor immediately if they 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 tear in the wall of a blood vessel.
• If the patient has or has had damage to the smallest blood vessels (called microangiopathic hemolytic anemia). The patient should tell their doctor if they experience fever, fatigue, weakness, bruising, bleeding, swelling, confusion, loss of vision, or seizures.
• If the patient has thyroid problems. Asikreba may cause thyroid problems. The patient should tell their doctor if they experience extreme fatigue, feel colder than others, or have a deepened 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 pancreas or gallbladder problems. The patient should tell their doctor if they 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 or has had liver problems. The patient should inform their doctor if they experience any of the following symptoms of liver problems while taking Asikreba: itching, yellowing of the eyes or skin, dark urine, and pain or discomfort in the right upper abdomen. The doctor should perform blood tests to check liver function before starting treatment with Asikreba, during treatment, and if there are any clinical signs.

The doctor will monitor kidney function if the patient has or has had kidney problems.

• If the patient is going to have surgery or has recently had surgery. Asikreba may affect wound healing. The medicine is usually stopped in patients before surgery. The doctor will decide when to restart Asikreba.
• The patient is advised to have a dental check-up before starting treatment with Asikreba:
• If the patient experiences 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, they should immediately inform their oncologist and dentist.
• If the patient needs invasive dental treatment or oral surgery, they should inform their dentist about taking Asikreba, especially if they are also taking or have taken intravenous bisphosphonates. Bisphosphonates are medicines 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 Asikreba, 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. The patient should contact their doctor immediately if they experience symptoms of infection around a skin lesion, including fever, pain, redness, swelling, or discharge of pus or blood. These disorders usually resolve after stopping treatment with 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 may progress to widespread blisters or peeling of the skin and can be life-threatening. If the patient experiences a rash or the above-mentioned skin symptoms, they should contact their doctor immediately.
• If the patient has or has had seizures. The patient should inform their doctor as soon as possible if they experience high blood pressure, headache, or loss of vision.
• If the patient has diabetes. In patients with diabetes, blood sugar levels should be regularly checked to assess whether the dose of the anti-diabetic medicine needs to be adjusted to minimize the risk of low blood sugar. The patient should inform their doctor as soon as possible if they experience symptoms of low blood sugar (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

The patient should tell their doctor or pharmacist about all medicines they are taking, have recently taken, or might take, including those obtained without a prescription.

Some medicines may affect the levels of Asikreba in the body. The patient should inform their doctor if they are taking medicines containing the following active substances:

• Ketoconazole, 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

The patient should not drink grapefruit juice while taking Asikreba.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a baby, they should consult their doctor or pharmacist before taking this medicine.

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

Women who are breastfeeding should inform their doctor. They should not breastfeed while taking Asikreba.

Driving and using machines

If the patient experiences dizziness or extreme fatigue, they should 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 essentially '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 allergic reactions.

3. How to take Asikreba

This medicine should always be taken exactly as prescribed by the doctor. If the patient is unsure, they should ask their doctor.

The doctor will prescribe a dose suitable for the individual patient, depending on the type of cancer.

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

The doctor will determine the appropriate dose for the individual patient 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 the patient has taken a dose higher than recommended, they should contact their doctor immediately. Treatment may be necessary.

Missing a dose of Asikreba

The patient should 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.

The patient should contact their doctor immediately if they experience any of the following serious side effects (see also Important information before taking Asikreba):

Heart problems. The patient should tell their doctor if they feel extremely tired, have shortness of breath, or swelling of the feet or ankles. These may be symptoms of heart problems, which can include heart failure and heart muscle problems (cardiomyopathy).

Lung problems or breathing difficulties. The patient should tell their doctor if they 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. The patient should tell their doctor if they experience changes in urination frequency or inability to urinate, which may be a sign of kidney failure.

Bleeding. The patient should tell their doctor if they experience any of the following symptoms or severe bleeding during treatment with Asikreba: stomach pain and swelling (abdomen), vomiting blood, black and tarry stools, blood in the urine, headache, or changes in consciousness, coughing up blood or bloody sputum from the lungs or airways.

Tumor lysis syndrome leading to intestinal perforation. The patient should tell their doctor if they experience severe stomach pain, fever, nausea, vomiting, blood in the stool, or changes in bowel habits.

Other side effects of Asikreba 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, 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 disturbances, stomach upset, nausea, vomiting, diarrhea, constipation, abdominal pain and/or swelling.
• 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.
• Coughing.
• Fever.
• Sleep disturbances.

Common: may affect up to 1 in 10 people

• Blood clots in blood vessels.
• Insufficient blood supply to the heart due to 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 serious complication of infection (sepsis) that can lead to tissue damage, organ failure, and death.
• Low blood sugar levels (see section 2).
• Protein loss in the urine, sometimes causing swelling.
• Flu-like symptoms.
• Abnormal blood test results, including pancreatic and liver enzymes.
• High levels of uric acid in the blood.
• Hemorrhoids, anal pain, gum bleeding, difficulty swallowing, or loss of swallowing ability.
• Burning or painful 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, feeling of nasal congestion.
• Excessive tearing.
• Skin sensation disturbances, itching, skin peeling, and/or inflammation, blisters, acne, nail discoloration, hair loss.
• Sensation disturbances in the limbs.
• Disturbances related to increased or decreased sensitivity, 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 rhythm or electrical activity.
• Fluid accumulation around the heart (pericardial effusion).
• Liver failure.
• Stomach pain (abdomen) caused by pancreatitis.
• Tumor lysis syndrome leading to intestinal perforation (see above).
• Inflammation of the gallbladder (with or without gallstones).
• Formation of abnormal connections between one body cavity and another or with the skin.
• 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. These may be symptoms of jawbone damage (osteonecrosis), see section 2.
• Overproduction 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 colitis.

Rare: may affect up to 1 in 1000 people

• Severe skin and/or mucous membrane reactions (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 levels of potassium, uric acid, and phosphorus, and low levels of calcium 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 loss of vision (reversible posterior leukoencephalopathy syndrome).
• Painful skin ulcers (pyoderma gangrenosum).
• Hepatitis.
• Thyroid inflammation.
• Damaged smallest blood vessels (microangiopathic hemolytic anemia).

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

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

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, 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.

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

By reporting side effects, more information can be gathered on the safety of the medicine.

5. How to store Asikreba

The medicine should be stored out of 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 storage precautions for this 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. The patient should ask their pharmacist how to dispose of medicines they no longer use. This will help protect the environment.

6. Contents of the packaging 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 Capsule contents: povidone K25, mannitol, sodium croscarmellose, magnesium stearate Capsule shell: gelatin, iron oxide red (E172), titanium dioxide (E171), iron oxide black (E172) Printing ink: shellac, propylene glycol, sodium hydroxide, povidone, titanium dioxide (E171).

Asikreba, 25 mg, hard capsules

Capsule contents: povidone K25, mannitol, sodium croscarmellose, magnesium stearate

Capsule shell: gelatin, titanium dioxide (E171), iron oxide red (E172), iron oxide black (E172), iron oxide yellow (E172)

Printing ink: shellac, propylene glycol, sodium hydroxide, povidone, titanium dioxide (E171)

Asikreba, 37.5 mg, hard capsules

Capsule contents: povidone K25, mannitol, sodium croscarmellose, magnesium stearate

Capsule shell: gelatin, orange yellow FCF (E110), tartrazine (E102), titanium dioxide (E171)

Printing ink: shellac, propylene glycol, ammonium hydroxide, iron oxide black (E172), potassium hydroxide

Asikreba, 50 mg, hard capsules

Capsule contents: povidone K25, mannitol (E421), sodium croscarmellose, magnesium stearate

Capsule shell: gelatin, titanium dioxide (E171), iron oxide yellow (E172), iron oxide red (E172), iron oxide black (E172)

Printing ink: 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 printing 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 printing 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 printing 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 printing 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 further information about this medicine, please 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: