Leuzek

Package leaflet: Information for the patient

Leuzek, 400 mg, hard capsules
Imatinibum
Please read the entire leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

1. What Leuzek is and what it is used for

Leuzek is available as hard gelatin capsules containing the active substance imatinib. The medicine works by inhibiting the growth of abnormal cells in the diseases listed below, including certain types of cancer.
Leuzek is used in adults, children, and adolescents for the treatment of the following conditions:

• Chronic myeloid leukaemia (CML) in blast crisis. Leukaemia is a cancer of white blood cells. White blood cells help the body fight infections. Chronic myeloid leukaemia is a type of leukaemia in which certain abnormal white blood cells (called myeloid cells) begin to multiply uncontrollably. Blast crisis is the most advanced stage of this disease.
• Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph-positive ALL). Leukaemia is a cancer arising from white blood cells. Normally, white blood cells help the body fight infections. Acute lymphoblastic leukaemia is a type of leukaemia in which certain abnormal white blood cells (called lymphoblasts) begin to multiply uncontrollably. Leuzek inhibits the growth of these cells.

Leuzek is also used in children and adolescents for the treatment of:

• Newly diagnosed CML, when bone marrow transplantation is not considered as first-line therapy;
• Chronic phase CML after failure of interferon-alpha therapy, or in accelerated phase. The accelerated phase is a transitional stage between the chronic phase and blast crisis. This phase is considered the first sign of developing resistance to treatment.

Leuzek is also indicated for the treatment of adult patients with:

• Myelodysplastic/myeloproliferative disorders (MDS/MPD). These are blood disorders in which certain white blood cells begin to multiply uncontrollably. Leuzek inhibits the growth of these cells in certain subtypes of these diseases.
• Hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukaemia (CEL). These are blood disorders in which certain blood cells (called eosinophils) begin to multiply uncontrollably. Leuzek inhibits the growth of these cells in certain subtypes of these diseases.
• Dermatofibrosarcoma protuberans (DFSP). DFSP is a cancer of the skin and subcutaneous tissues in which certain cells begin to multiply uncontrollably. Leuzek inhibits the growth of these cells.

In the remainder of this leaflet, abbreviated names of these diseases will be used.
If you have any questions about how Leuzek works or why this medicine has been prescribed, please consult your doctor.

2. Important information before using Leuzek

Leuzek may only be prescribed by a physician experienced in the use of drugs used to treat blood cancers.
You must strictly follow the doctor's instructions, even if they differ from the general information provided in this leaflet.
When not to use Leuzek:

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

If this applies to the patient, the patient should inform the doctor before taking Leuzek.
If the patient suspects they may be allergic but is not certain, they should consult the doctor for advice.
Warnings and precautions
Before starting Leuzek, discuss the following with your doctor:

• if the patient has or has ever had liver, kidney, or heart disease.
• if the patient is taking levothyroxine after thyroid removal.
• if the patient has ever had or may currently have hepatitis B virus infection; this is because Leuzek may cause reactivation of hepatitis B virus, which in some cases can be fatal; patients will be closely monitored by the doctor for signs of this infection before starting treatment.
• if the patient develops bruising, bleeding, fever, fatigue, or confusion while taking Leuzek, contact the doctor immediately. These may be symptoms of a blood vessel disorder called thrombotic microangiopathy (TMA).

If any of the above points apply to the patient, the patient should inform the doctor before taking Leuzek.
While taking Leuzek, the patient may become more sensitive to sunlight. It is important to cover sun-exposed skin areas and use sunscreen products with a high sun protection factor (SPF). These precautions should also be applied to children.
While taking Leuzek, the patient should immediately inform the doctor about rapid weight gain. Leuzek may cause fluid retention (severe fluid retention).
During treatment with Leuzek, the doctor will perform regular check-ups to monitor whether treatment with Leuzek is effective. Additionally, blood tests and body weight measurements will be performed regularly during treatment.
Children and adolescents
Leuzek is also used to treat children and adolescents with CML. There is no data available on the use of Leuzek in children under 2 years of age with CML. Experience with use in children with Ph+ ALL is limited, and experience with use in children with MDS/MPD, DFSP, and HES/CEL is very limited.
In some children and adolescents taking Leuzek, growth may be slower than normal. The doctor will monitor growth during regular visits.
Leuzek with other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including any medicines the patient plans to use, even those available without a prescription (e.g., paracetamol) and herbal medicines (e.g., St. John's wort). Some medicines may affect how Leuzek works when used at the same time. They may increase or decrease the effect of Leuzek, potentially leading to increased side effects or making Leuzek less effective. Leuzek may similarly affect certain other medicines.
Inform the doctor if the patient is taking medicines to prevent blood clots.
Pregnancy, breastfeeding, and fertility

• If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult the doctor before using this medicine.
• Use of Leuzek during pregnancy is not recommended unless absolutely necessary, as it may be harmful to the unborn child. The doctor will inform the patient about the potential risks associated with using Leuzek during pregnancy.
• Women who could become pregnant are advised to use effective contraception during treatment with Leuzek and for 15 days after stopping treatment.
• Breastfeeding must not be used during treatment with Leuzek and for 15 days after treatment ends, as it may harm the infant.
• Patients concerned about fertility during treatment with Leuzek should consult their doctor.

Driving and operating machinery
The patient may experience dizziness, drowsiness, or blurred vision while taking this medicine. In such cases, the patient should refrain from driving and operating machinery until feeling well again.
Leuzek contains a colouring agent called sunset yellow (E110)
The colouring agent in this medicine may cause allergic reactions.

3. How to use Leuzek

Your doctor has prescribed Leuzek because of the patient's serious condition. Leuzek may help improve this condition.
This medicine should always be taken exactly as directed by the doctor or pharmacist. The medicine should be taken for as long as your doctor recommends. If you have any doubts, consult your doctor or pharmacist.
Leuzek should be continued until your doctor decides to stop treatment. If the patient cannot take the medicine as directed, or if the patient thinks they no longer need to take the medicine, contact the doctor immediately.

Recommended dose

Use in adults
Your doctor will determine exactly how many Leuzek capsules should be taken.

• For treatment of blast phase CML: The initial dose is usually 600 mg, depending on the patient's condition:
  600 mg taken as one 400 mg capsule plus two 100 mg capsules once daily.

In the treatment of blast phase CML, your doctor may prescribe a higher or lower dose depending on the response to treatment. If the daily dose is 800 mg (2 capsules), take one capsule in the morning and one in the evening.

• For treatment of Ph-positive ALL: The initial dose is 600 mg, taken as one 400 mg capsule plus two 100 mg capsules once daily.
• For treatment of MDS/MPD: The initial dose is 400 mg, taken as one capsule once daily.
• For treatment of HES/CEL: The initial dose is 100 mg, taken as one 100 mg capsule once daily. Your doctor may decide to increase the dose to 400 mg, taken as one 400 mg capsule once daily, depending on the patient's response to treatment.
• For treatment of DFSP: The daily dose is 800 mg (2 capsules), taken as one capsule in the morning and one in the evening.

Use in children and adolescents
Your doctor will determine how many Leuzek capsules should be given to the child. The amount of Leuzek depends on the child's condition, body weight, and height. The total daily dose for children and adolescents must not exceed 800 mg in the treatment of CML and 600 mg in the treatment of Ph-positive ALL. The dose may be taken once daily or divided into two doses (half in the morning and half in the evening).

When and how to take Leuzek

• Leuzek should be taken with food, which may help protect the patient from stomach problems while taking Leuzek.

• Swallow the capsules whole with a large glass of water. Do not open or crush the capsules unless the patient has difficulty swallowing (e.g., in children).

• If the patient cannot swallow the capsules, the capsule contents may be dispersed in approximately 50 ml (for a 400 mg capsule) or 200 ml (for a 400 mg capsule) of non-carbonated water or apple juice (mix thoroughly with a spoon until the contents are completely dissolved, then drink the entire contents of the glass immediately).

• Women who are pregnant or may become pregnant and who open capsules should handle the contents with care: avoid contact of the powder with skin and eyes, and do not inhale it. Hands should be washed immediately after opening capsules.

How long to take Leuzek
Leuzek should be taken every day for as long as your doctor recommends.

Accidental overdose of Leuzek
If too many capsules are taken by accident, immediately inform your doctor. The patient may require medical attention. Bring the medicine packaging with you.

Missed dose of Leuzek

• If a dose is missed, take it as soon as possible. However, if it is almost time for the next dose, skip the missed dose.
• Then continue with the regular dosing schedule.
• Do not take a double dose to make up for a missed dose.

If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
They are usually mild to moderate.
Some side effects may be serious. You must inform your doctor immediately if any of the following symptoms occur:
Very common (occurring in more than 1 in 10 patients) or common (occurring in fewer than 1 in 10 patients)
side effects:

• Rapid weight gain. Leuzek may cause fluid retention (severe fluid retention).
• Signs of infection such as fever, severe chills, sore throat, and mouth ulcers. Leuzek may reduce the number of white blood cells in the blood, making the patient more susceptible to infections.
• Unexpected bleeding or bruising (without injury).

Uncommon (occurring in fewer than 1 in 100 patients) or rare (occurring in fewer than 1 in 1000 patients)
side effects:

• Chest pain, irregular heartbeat (symptoms of heart problems).
• Cough, difficulty breathing, or pain when breathing (symptoms of lung problems).
• Feeling faint, dizziness, or fainting (symptoms of low blood pressure).
• Nausea with loss of appetite, dark urine, yellowing of the skin or eyes (symptoms of liver disease).
• Rash, redness of the skin with blisters on the lips, around the eyes, on the skin, or in the mouth, skin peeling, fever, raised red or purple spots on the skin, itching, burning sensation, pustular rash (symptoms of skin problems).
• Severe abdominal pain, presence of blood in vomit, stool, or urine, black stools (symptoms of gastrointestinal disorders).
• Markedly reduced urine output, feeling thirsty (symptoms of kidney problems).
• Nausea with diarrhoea and vomiting, abdominal pain, or fever (symptoms of intestinal problems).
• Severe headache, weakness or paralysis of limbs or face, difficulty speaking, sudden loss of consciousness (symptoms of nervous system problems such as bleeding or swelling within the skull/brain).
• Pale skin, feeling tired and breathless, and dark-coloured urine (symptoms of red blood cell deficiency).
• Eye pain or blurred vision, bleeding in the eye.
• Hip pain or difficulty walking.
• Numbness or cold sensation in fingers (symptoms of Raynaud's syndrome).
• Sudden swelling and redness of the skin (symptoms of skin infection known as connective tissue inflammation).
• Hearing difficulties.
• Muscle weakness and cramps with irregular heartbeat (symptoms of changes in potassium levels in the patient's blood).
• Bruising.
• Stomach pain with nausea.
• Muscle cramps associated with fever, red-brown discoloration of urine, muscle pain and weakness (symptoms of muscle problems).
• Pelvic pain, sometimes with nausea and vomiting, sudden vaginal bleeding, dizziness or fainting due to low blood pressure (symptoms of ovarian or uterine problems).
• Nausea, shortness of breath, irregular pulse, cloudy urine, fatigue and (or) joint complaints accompanied by abnormal laboratory test results (e.g. high levels of potassium, uric acid and calcium, and low levels of phosphorus in the blood).
• Blood clots in small blood vessels (thrombotic microangiopathy).
• Painful red nodules on the skin, skin pain, redness of the skin (inflammation of subcutaneous fat tissue).

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

• Co-occurrence of widespread, severe rash, nausea, fever, high count of certain white blood cells, or yellowing of the skin or eyes (jaundice) with shortness of breath, chest pain/discomfort, markedly reduced urine output, and thirst, etc. (symptoms of an allergic reaction related to treatment).
• Chronic kidney failure.
• Reactivation of hepatitis B virus infection in patients who have previously had this disease.

If any of the above side effects occur, you must immediately inform your doctor.
Other possible side effects may include:
Very common side effects (occurring in more than 1 in 10 patients):

• Headache or fatigue.
• Nausea, vomiting, diarrhoea, or indigestion.
• Rash.
• Muscle cramps, muscle or bone pain during or after discontinuation of Leuzek.
• Swelling, e.g. of ankles or around the eyes.
• Weight gain. If any of these symptoms become severe, you must inform your doctor.

Common side effects (occurring in fewer than 1 in 10 patients):

• Loss of appetite, weight loss, or taste disturbances.
• Dizziness or weakness.
• Sleep disturbances (insomnia).
• Eye discharge with itching, redness, and swelling (conjunctivitis), excessive tearing, or blurred vision.
• Nosebleeds.
• Abdominal pain or swelling, bloating with passing wind, heartburn, or constipation.
• Itching.
• Excessive hair loss or thinning.
• Numbness of hands or feet.
• Mouth ulcers.
• Joint pain with swelling.
• Dry mouth, dry skin, or dry eyes.
• Decreased or increased skin sensitivity.
• Hot flushes, chills, or night sweats. If any of these symptoms become severe, you must inform your doctor.

Not known (frequency cannot be estimated from available data):

• Redness and (or) swelling of the palms and soles, which may be accompanied by tingling and burning pain.
• Skin changes with pain and/or blister formation.
• Slowed growth in children and adolescents.

If any of the symptoms listed above worsen, you must inform your doctor.
Reporting of side effects
If any side effects occur, including any side effects not listed in this leaflet, you should inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the 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 on the safety of this medicine can be collected.

5. How to store Leuzek

Keep this medicine out of sight and reach of children.
Store below 30°C.
Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the month indicated.
Do not use the packaging if it is damaged or shows signs of tampering.
Medicines must 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 package and other information

What Leuzek contains

• The active substance is imatinib. Each Leuzek capsule contains 400 mg of imatinib in the form of imatinib mesylate.
• Other components: capsule shell ingredients: gelatin, titanium dioxide; printing ink ingredients: shellac, concentrated ammonium hydroxide, propylene glycol, orange yellow.

What Leuzek looks like and contents of the pack
400 mg: hard gelatin capsules, white or almost white, printed with "400".
Pack size: 30 capsules.
Marketing Authorisation Holder
Nobilus Ent Tomasz Koźluk
ul. Swarzewska 45
01-821 Warsaw
Poland
Manufacturer
NOBILUS ENT
ul. Swarzewska 45
01-821 Warsaw
Poland