Nilotinib Zentiva

Leaflet accompanying the packaging: information for the user

Nilotinib Zentiva, 150 mg, hard capsules

Nilotinib Zentiva, 200 mg, hard capsules

Nilotinib

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 this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Nilotinib Zentiva and what is it used for

What is Nilotinib Zentiva

Nilotinib Zentiva is a medicine that contains the active substance nilotinib.

What is Nilotinib Zentiva used for

Nilotinib Zentiva is used to treat a type of leukemia called chronic myeloid leukemia (CML) with a positive Philadelphia chromosome. CML is a blood cancer that causes the body to produce too many abnormal white blood cells.

How does Nilotinib Zentiva work

In patients with CML, a change in DNA (genetic material) leads to the production of a signal that causes the body to produce abnormal white blood cells. Nilotinib Zentiva blocks this signal and thereby prevents the production of these abnormal cells.

Monitoring treatment with Nilotinib Zentiva

During treatment, regular tests will be performed, including blood tests. These tests determine:

• the number of blood cells (white blood cells, red blood cells, and platelets) in the body to assess how Nilotinib Zentiva is tolerated.
• pancreatic and liver function in the body to assess how Nilotinib Zentiva is tolerated.
• electrolyte levels in the body (potassium, magnesium), which are important for heart function.
• blood sugar and fat levels.

The heart rate will also be monitored using a device that measures the electrical activity of the heart (a test called an EKG).

The doctor will regularly evaluate the treatment results and decide whether the patient should continue taking Nilotinib Zentiva. If the patient finds out that they need to stop treatment with this medicine, the doctor will continue to monitor the CML condition and may recommend that the patient resume treatment with Nilotinib Zentiva if their condition requires it.

2. Important information before taking Nilotinib Zentiva

Follow the doctor's instructions carefully. They may differ from the general information contained in this leaflet.

When not to take Nilotinib Zentiva

• if the patient is allergic to nilotinib or any of the other ingredients of this medicine (listed in section 6). If the patient suspects that they may be allergic, they should tell their doctor before starting treatment with Nilotinib Zentiva.

Warnings and precautions

Before starting treatment with Nilotinib Zentiva, the patient should discuss the following with their doctor or pharmacist:

• if the patient has previously experienced cardiovascular events such as heart attack, chest pain (angina), stroke, or poor circulation to the legs (claudication) or if the patient has risk factors for cardiovascular disease, such as high blood pressure (hypertension), diabetes, or lipid disorders;
• if the patient has heart problems, such as abnormal electrical activity called "QT interval prolongation";
• if the patient is taking medicines that lower cholesterol levels in the blood (statins) or affect heart function (anti-arrhythmic drugs) or liver function (see "Other medicines and Nilotinib Zentiva");
• if the patient has low potassium or magnesium levels;
• if the patient has liver or pancreas problems;
• if the patient experiences symptoms such as easy bruising, fatigue, or shortness of breath or if they experience recurring infections;
• if the patient has had surgery to remove the entire stomach (total gastrectomy);
• if the patient has had or may have a hepatitis B virus infection; this is because Nilotinib Zentiva may cause the hepatitis B virus to become active again, which can be fatal in some cases; patients will be closely monitored by their doctor for signs of this infection before starting treatment.

During treatment with Nilotinib Zentiva

• if the patient experiences loss of consciousness (fainting) or irregular heartbeat, they should tell their doctor immediately, as this may be a sign of a serious heart condition. QT interval prolongation or irregular heartbeat can lead to sudden death. Sudden death has been reported in patients taking nilotinib.
• if the patient experiences: rapid heartbeat, severe weakness or paralysis, seizures, or sudden changes in thinking or concentration, they should tell their doctor immediately, as these may be symptoms of a condition called tumor lysis syndrome; tumor lysis syndrome has been rarely reported in patients treated with nilotinib.
• if the patient experiences chest pain or discomfort, numbness or weakness, difficulty walking or speaking, pain, discoloration, or feeling of coldness in a limb, they should tell their doctor immediately, as these may be symptoms of cardiovascular events. Cardiovascular events have been reported in patients taking nilotinib, including peripheral arterial disease, ischemic heart disease, and stroke.
• if the patient experiences swelling of the feet or hands, generalized edema, or rapid weight gain, they should tell their doctor, as these may be symptoms of severe fluid retention. Severe fluid retention has been reported in patients treated with Nilotinib Zentiva. Parents of children treated with Nilotinib Zentiva should inform their doctor if any of the above situations apply to their child.

Children and adolescents

Nilotinib Zentiva is used to treat children and adolescents with CML. There is limited experience with the use of this medicine in children under 2 years of age. There is limited experience with the use of Nilotinib Zentiva in children under 10 years of age with newly diagnosed disease, and there is limited experience in patients under 6 years of age who have stopped responding to previous CML treatment.

Some children and adolescents taking Nilotinib Zentiva may grow more slowly than normal.

The doctor will monitor growth during regular visits.

Nilotinib Zentiva and other medicines

Nilotinib Zentiva may affect the way other medicines work.

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. This is especially important for medicines such as:

• anti-arrhythmic drugs used to treat irregular heart rhythms;
• chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin - these are medicines that may have a negative effect on the heart's electrical activity;
• ketokonazole, itraconazole, voriconazole, clarithromycin, telithromycin - used to treat infections;
• ritonavir - a protease inhibitor used to treat HIV infections;
• carbamazepine, phenobarbital, and phenytoin - used to treat epilepsy;
• rifampicin - used to treat tuberculosis;
• St. John's Wort (also known as Hypericum perforatum) - a herbal product used to treat depression and other conditions;
• midazolam - used as a sedative before surgery;
• alfentanil and fentanyl - used to treat pain and as sedatives before and during surgery or medical procedures;
• cyclosporine, sirolimus, and tacrolimus - medicines used to suppress the body's immune system and prevent infection, often used to prevent organ rejection after transplantation;

The patient should also tell their doctor if they are already taking Nilotinib Zentiva and have been prescribed a new medicine that has not been taken with Nilotinib Zentiva before.

Taking Nilotinib Zentiva with food and drink

Do not take Nilotinib Zentiva with food.Food can increase the absorption of Nilotinib Zentiva and increase the level of Nilotinib Zentiva in the blood, even to a harmful level.

Do not drink grapefruit juice or eat grapefruit.They can increase the level of Nilotinib Zentiva in the blood, even to a harmful level.

Pregnancy and breastfeeding

• Women who may become pregnant should use highly effective contraception during treatment and for up to two weeks after treatment is stopped.
• Nilotinib Zentiva should not be used during breastfeeding and for two weeks after the last dose.If the patient is breastfeeding, they should inform their doctor. If the patient is pregnant, breastfeeding, or thinks they may be pregnant, or is planning to have a baby, they should consult their doctor or pharmacist before taking this medicine.

Driving and using machines

If the patient experiences side effects such as dizziness or vision disturbances that may affect their ability to drive or operate machinery, they should stop driving or operating machinery until these side effects have resolved.

Nilotinib Zentiva contains lactose

This medicine contains lactose (also known as milk sugar). If the patient has been diagnosed with intolerance to some sugars, they should contact their doctor before taking this medicine.

3. How to take Nilotinib Zentiva

This medicine should always be taken exactly as prescribed by the doctor or pharmacist. If the patient has any doubts, they should consult their doctor or pharmacist.

What dose of Nilotinib Zentiva to take

Adult patients

• Patients with newly diagnosed CML:The recommended dose is 600 mg per day. This dose is achieved by taking two 150 mg hard capsules twice a day.
• Patients who have stopped responding to previous CML treatment:The recommended dose is 800 mg per day. This dose is achieved by taking two 200 mg hard capsules twice a day.

Children and adolescents

• The dose given to the child depends on the child's weight and growth. The doctor will calculate the correct dose to be taken and tell the patient which capsules and how many capsules of Nilotinib Zentiva to give to the child. The total daily dose given to the child should not exceed 800 mg.

The doctor may prescribe a lower dose depending on how the patient responds to treatment.

Elderly patients (65 years and older)

Nilotinib Zentiva can be given to patients 65 years and older at the same doses as other adults.

When to take Nilotinib Zentiva

The hard capsules should be taken:

• twice a day (approximately 12 hours apart);
• at least 2 hours after eating any food;
• the patient should wait 1 hour after taking the medicine before eating. If the patient has any doubts about when to take this medicine, they should consult their doctor or pharmacist. Nilotinib Zentiva should be taken at the same time every day to help the patient remember to take the capsules.

How to take Nilotinib Zentiva

• The hard capsules should be swallowed whole with water.
• The capsules should not be taken with food.
• The capsules should not be opened. If an adult or child is unable to swallow a whole capsule, they should use a different nilotinib medicine instead.

How long to take Nilotinib Zentiva

Nilotinib Zentiva should be taken every day for as long as the doctor recommends. Treatment is long-term. The doctor will regularly monitor the patient's condition to assess whether treatment is having the desired effect.

The doctor may consider stopping treatment with Nilotinib Zentiva based on specific criteria.

If the patient has any doubts about the duration of treatment with Nilotinib Zentiva, they should consult their doctor or pharmacist.

Taking a higher dose of Nilotinib Zentiva than recommended

If the patient takes more Nilotinib Zentiva than recommended or takes it by mistake, they should contact their doctor or go to the hospital immediately. The patient should show the doctor or hospital staff the packaging and leaflet. Medical attention may be necessary.

Missing a dose of Nilotinib Zentiva

If the patient misses a dose, they should take the next dose according to the scheduled plan. The patient should not take a double dose to make up for the missed capsules.

Stopping treatment with Nilotinib Zentiva

This medicine should be taken for as long as the doctor recommends. Stopping treatment with Nilotinib Zentiva without consulting a doctor may put the patient's life at risk. If the patient is considering stopping treatment with Nilotinib Zentiva, they should discuss this with their doctor, nurse, and/or pharmacist.

Doctor's recommendation to stop treatment with Nilotinib Zentiva

The doctor will regularly evaluate the treatment results using specific diagnostic tests and decide whether the patient should continue taking this medicine. If the patient is told to stop treatment with Nilotinib Zentiva, the doctor will continue to closely monitor the CML condition and may recommend that the patient resume treatment with Nilotinib Zentiva if their condition requires it.

If the patient has any further doubts about taking this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

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

Most side effects are mild to moderate and go away after a few days or weeks of treatment.

Some side effects can be serious.

• musculoskeletal pain: joint pain and muscle pain
• heart problems: chest pain or discomfort, high or low blood pressure, irregular heartbeat (fast or slow), palpitations, fainting, blue discoloration of the lips, tongue, or skin
• arterial occlusion: pain, discomfort, weakness, or cramping of the legs, which may be caused by reduced blood flow, ulcers on the legs or arms that heal slowly or not at all, and noticeable changes in skin color (blue or pale) or temperature (cooling) of the legs or arms, fingers, or toes
• hypothyroidism: weight gain, fatigue, hair loss, muscle weakness, feeling cold
• hyperthyroidism: rapid heartbeat, bulging eyes, weight loss, swelling of the front of the neck
• kidney or urinary tract problems: feeling thirsty, dry skin, irritability, dark urine, decreased urine output, difficult or painful urination, frequent urination, blood in the urine, abnormal urine color
• high blood sugar: excessive thirst, excessive urination, increased appetite with weight loss, feeling tired
• dizziness: dizziness or feeling of spinning
• pancreatitis: severe abdominal pain (in the middle or left side)
• skin problems: painful, red lumps, skin pain, redness of the skin, peeling of the skin, or blistering
• fluid retention: rapid weight gain, swelling of the hands, ankles, feet, or face
• migraine: severe headache, often accompanied by nausea, vomiting, and sensitivity to light
• blood problems: fever, easy bruising or bleeding for no apparent reason, severe or frequent infections, weakness for no apparent reason
• blood clots in the veins: swelling and pain in one part of the body
• nervous system problems: weakness or paralysis of limbs or face, difficulty speaking, severe headaches, vision, hearing, or feeling things that do not exist, changes in vision, loss of consciousness, confusion, disorientation, trembling, feeling of tingling, pain, or numbness
• lung problems: difficulty breathing or pain while breathing, cough, wheezing breath with or without fever, swelling of the feet or legs
• gastrointestinal problems: abdominal pain, nausea, vomiting, diarrhea, constipation, heartburn, acid reflux, abdominal swelling
• liver problems: yellowing of the skin and eyes, nausea, loss of appetite, dark urine
• hepatitis: recurrence (reactivation) of hepatitis B virus infection
• eye problems: vision disturbances, including blurred vision, double vision, or seeing flashes of light, decreased visual acuity, or loss of vision, blood in the eyes, increased sensitivity of the eyes to light, eye pain, redness, itching, or irritation

Some side effects are very common(may affect more than 1 in 10 people)

• diarrhea
• headache
• lack of energy
• muscle pain
• itching, rash
• nausea
• constipation
• vomiting
• hair loss
• limb pain, bone pain, and back pain after stopping treatment with Nilotinib Zentiva
• slowed growth in children and adolescents
• upper respiratory tract infection, including sore throat, runny nose, or stuffy nose, coughing
• low blood cell count (red blood cells, platelets) or low hemoglobin level
• high lipase levels in the blood (pancreatic function)
• high bilirubin levels in the blood (liver function)
• high alanine aminotransferase levels in the blood (liver enzymes)

Some side effects are common(may affect up to 1 in 10 people)

• pneumonia
• abdominal pain, discomfort in the stomach after eating, bloating, abdominal swelling
• bone pain, muscle cramps
• pain (including neck pain)
• dry skin, acne, decreased skin sensitivity
• weight gain or loss
• insomnia, depression, anxiety
• night sweats, excessive sweating
• general feeling of being unwell
• nosebleeds
• gout: joint pain and swelling
• erectile dysfunction
• flu-like symptoms
• bronchitis
• ear pain, ringing in the ears (also known as tinnitus), hearing loss
• hives
• menstrual irregularities
• itching of hair follicles
• vaginal or oral thrush
• conjunctivitis: eye discharge with itching, redness, and swelling
• eye irritation, redness of the eyes
• high blood pressure: high blood pressure, headache, dizziness
• flushing of the face
• peripheral arterial disease: pain, discomfort, weakness, or cramping of the legs, which may be caused by reduced blood flow, ulcers on the legs or arms that heal slowly or not at all, and noticeable changes in skin color (blue or pale) or temperature (cooling) of the legs or arms (these symptoms may indicate arterial occlusion in the affected limb)
• difficulty breathing, ulcers in the mouth with inflammation of the gums (also known as stomatitis)
• high amylase levels in the blood (pancreatic function)
• high creatinine levels in the blood (kidney function)
• high alkaline phosphatase or creatine phosphokinase levels in the blood
• high aspartate aminotransferase levels in the blood (liver enzymes)
• high gamma-glutamyltransferase levels in the blood (liver enzymes)
• leukopenia or neutropenia: low white blood cell count
• high platelet or white blood cell count in the blood
• low magnesium, potassium, sodium, calcium, or phosphorus levels in the blood
• high lipid levels in the blood (including cholesterol)
• high uric acid levels in the blood

Some side effects are uncommon(may affect up to 1 in 100 people)

• allergic reaction (hypersensitivity to Nilotinib Zentiva)
• dry mouth
• chest pain
• pain or discomfort in the side
• increased appetite
• breast enlargement in men
• herpes virus infection
• stiffness of the muscles and joints, joint swelling
• feeling of temperature changes (including feeling hot or cold)
• taste disturbances
• frequent urination
• gastritis: abdominal pain, nausea, vomiting, diarrhea, abdominal swelling
• memory loss
• skin cyst, skin thinning or thickening, skin discoloration
• psoriasis: thickened, red, silvery patches of skin
• increased sensitivity of the skin to light
• hearing loss
• gingivitis: bleeding gums, tenderness, or swelling of the gums
• high urea levels in the blood (kidney function)
• changes in blood protein levels (low globulin or presence of paraprotein)
• high unconjugated bilirubin levels in the blood
• high troponin levels in the blood

Some side effects are rare(may affect up to 1 in 1,000 people)

• redness and swelling of the hands and feet (also known as palmar-plantar erythrodysesthesia syndrome)
• oral thrush
• feeling of hardening or thickening of the breasts
• thyroid inflammation
• mood disturbances or depression
• secondary hyperparathyroidism: bone and joint pain, frequent urination, abdominal pain, weakness, fatigue
• arterial stenosis in the brain: loss of vision affecting part or all of the field of vision in both eyes, double vision, dizziness (feeling of spinning), numbness or tingling, loss of coordination, dizziness, or confusion
• brain edema (possible headache and/or changes in mental status)
• optic neuritis: blurred vision, loss of vision
• heart problems (reduced ejection fraction): fatigue, discomfort in the chest, feeling of dizziness, pain, palpitations
• low insulin levels in the blood (hormone that regulates blood sugar levels)
• low C-peptide levels in the blood (pancreatic function)
• sudden death

The following side effects have been reported with an unknown frequency (cannot be estimated from the available data):

• heart problems (heart failure): shortness of breath, fatigue at rest, irregular heartbeat, discomfort in the chest, feeling of dizziness, pain, palpitations, excessive urination, swelling of the feet, ankles, and abdomen.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring 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.

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

5. How to store Nilotinib Zentiva

• 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 and blister after EXP. The expiry date refers to the last day of the month stated.
• This medicine does not require any special storage conditions.
• 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 that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Nilotinib Zentiva contains

• The active substance of Nilotinib Zentiva is nilotinib.

Each hard capsule contains 150 mg of nilotinib (as dihydrochloride monohydrate).

The other ingredients are:

Capsule contents: lactose monohydrate, crospovidone type A (E1202), colloidal silicon dioxide (E551), magnesium stearate (E470b)

Capsule shell: hypromellose (E464), carrageenan (E407), potassium chloride (E508), erythrosine (E127), yellow iron oxide (E172), red iron oxide (E172), titanium dioxide (E171), purified water

Printing ink: shellac (E904), propylene glycol (E1520), potassium hydroxide (E525), black iron oxide (E172)

Each hard capsule contains 200 mg of nilotinib (as dihydrochloride monohydrate).

The other ingredients are:

Capsule contents: lactose monohydrate, crospovidone type A (E1202), colloidal silicon dioxide (E551), magnesium stearate (E470b)

Capsule shell: hypromellose (E464), carrageenan (E407), potassium chloride (E508), yellow iron oxide (E172), titanium dioxide (E171), purified water

Printing ink: shellac (E904), propylene glycol (E1520), potassium hydroxide (E525), black iron oxide (E172)

What Nilotinib Zentiva looks like and contents of the pack

Nilotinib Zentiva 150 mg is a red, non-transparent, hard capsule (capsule) size 1 (approximately 19.3 mm in length), with a black horizontal print "150 mg" on the body. The hard capsules are filled with a powder that is white to yellowish in color.

Nilotinib Zentiva 200 mg is a light yellow, non-transparent, hard capsule (capsule) size 0 (approximately 21.4 mm in length), with a black horizontal print "200 mg" on the body. The hard capsules are filled with a powder that is white to yellowish in color.

Nilotinib Zentiva is available in the following packaging:

Nilotinib Zentiva 150 mg hard capsules

• Unit packs containing 28 or 112 hard capsules in blisters, in a cardboard box.
• Bulk packs containing 112 (4 packs of 28) hard capsules or 120 (3 packs of 40) hard capsules, in a cardboard box.

Nilotinib Zentiva 200 mg hard capsules

• Unit packs containing 28 or 112 hard capsules in blisters, in a cardboard box.
• Bulk packs containing 112 (4 packs of 28) hard capsules or 120 (3 packs of 40) hard capsules, in a cardboard box. Not all pack sizes may be marketed.

Marketing authorization holder

Zentiva, k.s.

U kabelovny 130

Dolní Měcholupy

102 37 Prague 10

Czech Republic

Manufacturer

PharOS MT Ltd.

HF62X, Hal Far Industrial Estate,

Birzebbugia BBG3000,

Malta

PharOS Pharmaceutical Oriented Services Ltd.

Lesvou Street End, Thesi Loggos Industrial Zone,

Metamorfossi, 144 52,

Greece

This medicine is authorized in the Member States of the European Economic Area under the following names:

Hungary: Nilotinib Zentiva 50mg kemény kapszula, Nilotinib Zentiva 150mg kemény kapszula, Nilotinib Zentiva 200mg kemény kapszula

Austria: Nilotinib Zentiva 150 mg Hartkapseln, Nilotinib Zentiva 200 mg Hartkapseln

Bulgaria: Нилотиниб Зентива 150 mg твърди капсули, Нилотиниб Зентива 200 mg твърди капсули

Croatia: Nilotinib Zentiva 150 mg tvrde kapsule, Nilotinib Zentiva 200 mg tvrde kapsule

Estonia, Czech Republic, Poland, Portugal: Nilotinib Zentiva

Lithuania: Nilotinib Zentiva 150 mg kietosios kapsulės, Nilotinib Zentiva 200 mg kietosios kapsulės

Latvia: Nilotinib Zentiva 150 mg cietas kapsulas, Nilotinib Zentiva 200 mg cietas kapsulas

Romania: Nilotinib Zentiva 150 mg capsule, Nilotinib Zentiva 200 mg capsule

Slovakia: Nilotinib Zentiva 150 mg, Nilotinib Zentiva 200 mg

For more information about this medicine, the patient should contact the representative of the marketing authorization holder in Poland:

Zentiva Polska Sp. z o.o.

ul. Bonifraterska 17

00-203 Warsaw

tel.: +48 22 375 92 00

Date of last revision of the leaflet:September 2024