Nibix

Package leaflet: Information for the patient

Nibix, 400 mg, hard capsules
Imatinibum
Read the entire leaflet carefully before taking the medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• 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. The 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, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

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

1. What Nibix is and what it is used for

Nibix is a medicine containing an active substance called imatinib. This medicine works by
inhibiting the growth of abnormal cells in the diseases listed below.
These include certain types of cancer.
Nibix is indicated for the treatment of adult patients and children with:

• Chronic myeloid leukaemia (CML). Leukaemia is a cancer originating from white blood cells. Normally, 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.
• Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph-positive ALL). Leukaemia is a cancer originating 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. Nibix inhibits the growth of these cells.

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

• Myelodysplastic/myeloproliferative diseases (MDS/MPD). These are blood disorders in which certain white blood cells begin to multiply uncontrollably. Nibix 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. Nibix inhibits the growth of these cells in certain subtypes of these diseases.
• Gastrointestinal stromal tumours (GIST). GIST is a tumour of the stomach and intestines. It arises due to uncontrolled growth of connective tissue cells in these organs.
• Dermatofibrosarcoma protuberans (DFSP). DFSP is a tumour of the skin and subcutaneous tissues in which certain cells begin to multiply uncontrollably. Nibix inhibits the growth of these cells.

In the remainder of this leaflet, the abbreviations of the diseases listed above will be used.
If you have any questions regarding how Nibix works or why it has been prescribed,
please consult your doctor.

2. Important information before using Nibix

Nibix is prescribed to patients only by physicians experienced in the use of drugs administered in the treatment of hematological malignancies or solid tumors.
It is essential to strictly follow the doctor's instructions, even if they differ from the general information provided in this leaflet.

When not to use Nibix

• if the patient is allergic to imatinib or to 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 Nibix.
In case of suspected allergy but uncertainty, medical advice should be sought.

Warnings and precautions
Before starting treatment with Nibix, the following should be discussed with the doctor:

• if the patient currently 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 Nibix may cause reactivation of hepatitis B virus, which in some cases may be fatal; patients will be closely monitored by the doctor for signs of this infection before starting treatment.
• if the patient experiences bruising, bleeding, fever, fatigue, or confusion while taking Nibix, the patient should contact the doctor immediately. These may be symptoms of damage to blood vessels called thrombotic microangiopathy (TMA). If any of the above points apply to the patient, the patient should inform the doctor before taking Nibix.

While taking Nibix, the patient may become more sensitive to sunlight. It is important to cover sun-exposed skin areas and to use sunscreen products with a high sun protection factor (SPF). These precautions should also be applied to children.
The patient should immediately inform the doctor if there is a rapid weight gain during treatment with Nibix. Nibix may cause fluid retention (severe fluid retention).

While taking Nibix, the patient's health status will be regularly assessed by the doctor to monitor the effectiveness of treatment. Blood tests and body weight measurements will be performed regularly during treatment with this medicine.

Children and adolescents
Nibix is also used in the treatment of children with CML. There is no experience with use in children with CML under 2 years of age.
Experience with use in children with Ph-positive ALL is limited, and experience with use in children with MDS/MPD, DFSP, GIST, and HES/CEL is very limited.
In some children and adolescents taking Nibix, growth may be slower than normal. The doctor will monitor growth during regular visits.

Nibix and other medicines
The patient should inform the doctor or pharmacist about all medicines currently used or recently used, as well as any medicines planned for use, including those available without a prescription (such as paracetamol) and herbal medicines (such as St. John's wort). Some medicines may affect the action of Nibix when taken concurrently. They may increase or decrease the effect of Nibix, potentially leading to increased adverse reactions or causing Nibix to be less effective. Nibix may also affect the action of certain other medicines in a similar way.
The patient should inform the doctor if they are taking medicines to prevent blood clots.

Pregnancy, breastfeeding, and fertility

• If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult the doctor before using this medicine.
• Nibix is not recommended for pregnant women unless absolutely necessary, as it may harm the unborn child. The doctor will explain the potential risks associated with taking Nibix during pregnancy.
• Women who could become pregnant should use an effective method of contraception during treatment with Nibix and for 15 days after stopping treatment.
• Breastfeeding should not be performed during treatment with Nibix and for 15 days after treatment ends, as it may harm the infant.
• Patients concerned about fertility during treatment with Nibix should consult their doctor.

Driving and operating machinery
While taking Nibix, dizziness, somnolence, or visual disturbances may occur. In such cases, the patient should not drive or operate tools or machinery until feeling well again.

Nibix contains monohydrate lactose
If the patient has been diagnosed with an intolerance to certain sugars, the patient should inform the doctor before using Nibix.

3. How to use Nibix

Your doctor has prescribed Nibix because of your serious medical condition. Nibix may help improve this condition.
However, this medicine should always be used exactly as recommended by your doctor or pharmacist. It is important to continue taking the medicine for as long as your doctor or pharmacist has advised. If you have any doubts, consult your doctor or pharmacist.
Do not stop taking Nibix unless your doctor tells you to do so. If you are unable to take the prescribed medicine or think you no longer need it, you should contact your doctor immediately.

What is the dose of Nibix?
Use in adult patients
Your doctor will determine the exact number of Nibix capsules to take.

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

For both CML and GIST treatment, your doctor may prescribe a higher or lower dose depending on your response to treatment. If the total daily dose is 800 mg (2 capsules), one capsule should be taken 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 your response to treatment.
• For treatment of DFSP: The daily dose is 800 mg (2 capsules), taken as one capsule in the morning and one capsule in the evening.

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

When and how to take Nibix

• Nibix should be taken with food to protect the stomach during treatment.
• Capsules should be swallowed whole with a large glass of water. Do not open or crush the capsules unless you have difficulty swallowing them (e.g., children).
• If you are unable to swallow the capsules, you may open them and dissolve the powder in a glass of still water or apple juice.
• Women who are pregnant or planning pregnancy should exercise particular caution when opening capsules. Avoid contact of the capsule contents with the eyes and inhalation of the powder. Wash hands immediately after opening the capsule.

How long to take Nibix
You should take Nibix every day for as long as your doctor advises.

Taking more Nibix than prescribed
Patients who have accidentally taken too many capsules should inform their doctor immediately, as they may require medical attention. Take the medicine packaging with you.

Missed dose of Nibix

• If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose.
• Then continue with your 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 adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
They are usually mild to moderate.
Some adverse reactions may be serious. You should tell your doctor immediately
if you experience any of the adverse reactions listed below.
Very common (may affect more than 1 in 10 people) or common (may affect less than 1 in 10 people):

• Rapid weight gain. Nibix may cause fluid retention in the body (severe fluid retention).
• Signs of infection, such as fever, severe chills, sore throat, and mouth ulcers. Nibix may reduce the number of white blood cells in the blood, which may increase the risk of infection.
• Unexpected bleeding or bruising (despite no injury).

Uncommon (may affect less than 1 in 100 people) or rare (may affect less than 1 in 1,000 people):

• 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, pale-coloured urine, yellowing of the skin or eyes (symptoms of liver problems).
• 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, blister-like rash (symptoms of skin problems).
• Severe abdominal pain, blood in vomit, stool, or urine, black stools (symptoms of stomach or intestinal 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 worsening vision, bleeding in the eyes.
• Bone or joint pain (symptoms of bone necrosis).
• Blisters on the skin or mucous membranes (symptoms of pemphigus).
• Numbness or cold sensation in fingers and toes (symptoms of Raynaud's syndrome).
• Sudden swelling and redness of the skin (symptoms of skin infection called cellulitis).
• 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 with fever, red-brown urine colour, 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 heartbeat, cloudy urine, fatigue and (or) joint discomfort with accompanying laboratory abnormalities (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).

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

• Co-occurrence of widespread, severe rash, nausea, fever, high number 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 feeling thirsty, etc. (symptoms of an allergic reaction related to treatment).
• Chronic kidney failure.
• Recurrence (reactivation) of hepatitis B virus infection (liver infection) in patients who previously had this disease.

If any of the above adverse reactions occur, you should immediately inform your doctor.
Other adverse reactions may include:
Very common (may affect more than 1 in 10 people):

• Headache or fatigue.
• Nausea, vomiting, diarrhoea, indigestion.
• Rash.
• Muscle or joint cramps, muscle or bone pain, during or after discontinuation of Nibix treatment.
• Swelling, such as swelling of the ankles or around the eyes.
• Weight gain. If any of the above symptoms worsen, you should inform your doctor.

Common (may affect less than 1 in 10 people):

• Loss of appetite, weight loss, or taste disturbances.
• Dizziness or weakness.
• Sleep difficulties (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.
• Dryness of the mouth, dry skin, or dry eyes.
• Decreased or increased skin sensitivity.
• Hot flushes, chills, or night sweats. If any of the above symptoms worsen, you should inform your doctor.

Uncommon (may affect no more than 1 in 100 people):

• Painful red nodules on the skin, skin pain, skin redness (inflammation of the fatty tissue beneath the skin).
• Cough, watery nasal discharge or blocked nose, feeling of heaviness or pain when pressing the area above the eyes or on both sides of the nose, nasal mucosa congestion, sneezing, sore throat, with or without headache (symptoms of upper respiratory tract infection).
• Severe headache felt as a pulsating pain or pulsation sensation, usually on one side of the head, often accompanied by nausea, vomiting, and sensitivity to light or sound (symptoms of migraine).
• Flu-like symptoms (influenza-like illness).
• Pain or burning sensation when passing urine, elevated body temperature, pain in the groin or pelvic area, red or brown urine colour, or cloudy urine (symptoms of urinary tract infection).
• Joint pain and swelling (symptoms of joint pain).
• Persistent feeling of sadness and loss of interest, preventing the patient from performing daily activities (symptoms of depression).
• Feeling nervous or anxious with somatic symptoms such as rapid heartbeat, sweating, trembling, dry mouth (symptoms of anxiety).
• Drowsiness/excessive sleepiness.
• Tremor or muscle twitching.
• Memory disturbances.
• Irresistible urge to move the legs (restless legs syndrome).
• Hearing noises (e.g. ringing, buzzing) in the ears not originating from outside (tinnitus).
• High blood pressure (hypertension).
• Belching.
• Inflammation of the lips.
• Difficulty swallowing.
• Increased sweating.
• Skin discolouration.
• Brittle nails.
• Red nodules or whiteheads forming around hair roots, which may cause pain, itching, or burning sensation (symptoms of folliculitis).
• Skin rash with skin peeling (exfoliative dermatitis).
• Breast enlargement (may occur in men or women).
• Dull pain and (or) heaviness in the testicles or lower abdomen, pain when passing urine, during sexual intercourse, or ejaculation, blood in urine (symptoms of testicular swelling).
• Inability to achieve or maintain an erection (erectile dysfunction).
• Heavy or irregular menstrual bleeding.
• Difficulty achieving/maintaining sexual arousal.
• Decreased libido.
• Nipple pain.
• General malaise.
• Viral infection, such as a cold.
• Lower back pain due to kidney disorders.
• Increased frequency of urination.
• Increased appetite.
• Pain or burning sensation in the upper abdomen and (or) chest (heartburn), nausea, vomiting, gastric acid reflux, feeling of fullness and bloating, black stools (symptoms of stomach ulcer).
• Joint and muscle stiffness.
• Abnormal laboratory test results. If any of the above symptoms worsen, you should inform your doctor.

Rare (may affect no more than 1 in 1,000 people):

• Confusion.
• Episode of seizure(s) and reduced consciousness (convulsions).
• Nail discolouration.

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

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

If any of the above symptoms worsen, you should inform your doctor.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, you should inform your doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring of 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.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Nibix medicine

• Keep this medicine out of sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and blister pack following the term "Expiry date (EXP):". The expiry date refers to the last day of the specified month.
• Do not store above 30°C.
• Do not use the medicine if the packaging 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 practice helps protect the environment.

6. Contents of the pack and other information

What Nibix contains

• The active substance is imatinib (as mesilate). Each Nibix capsule contains 400 mg of imatinib (as mesilate).
• The other ingredients are: crospovidone type A, lactose monohydrate, and magnesium stearate.
• The capsule shell contains gelatin, yellow iron oxide (E 172), titanium dioxide (E 171), and red iron oxide (E 172).

What Nibix looks like and contents of the pack
Nibix 400 mg hard capsules are caramel-coloured, gelatin capsules of size "00". It is available in packs containing 10, 30, 90 or 100 capsules. Not all pack sizes may be available in the country.

Marketing Authorisation Holder
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Poland

Manufacturer/Importer
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Poland
UAB Norameda
Meistrų 8a, Vilnius LT-02189
Lithuania
Gedeon Richter Plc.
Gyömrői út 19-21., 1103, Budapest
Hungary

For further information about this medicinal product, please contact the Marketing Authorisation Holder.

This medicinal product is authorised for sale in the European Economic Area countries under the following names:
Poland Nibix
Estonia Glipox
Hungary Nibix 400 mg kemény kapszula