Patient Information Leaflet: Package Insert

Nilotinib Stada 50 mg Hard Capsules EFG

Nilotinib Stada 150 mg Hard Capsules EFG

Nilotinib Stada 200 mg Hard Capsules EFG

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

What is Nilotinib Stada

Nilotinib Stada is a medication that contains an active ingredient called nilotinib.

What is Nilotinib Stada used for

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

Nilotinib is used in adult and pediatric patients with newly diagnosed CML or in patients with CML who no longer benefit from previous treatment, including imatinib..Nilotinib is also used in adult and pediatric patients who have experienced severe adverse effects with previous treatment and cannot continue using it.

How Nilotinib Stada works

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

Monitoring during Nilotinib Stada treatment

Regular monitoring will be performed during treatment, including blood tests. These tests will control:

• the amount of blood cells in the body (white blood cells, red blood cells, and platelets) to check if nilotinib is well tolerated.
• the function of the pancreas and liver of the body to check if nilotinib is well tolerated.
• the body's electrolytes (potassium, magnesium). These are important for heart function.
• the level of sugar and fats in the blood.

The heart rate will also be monitored using a machine that measures the heart's electrical activity (an electrocardiogram, or ECG).

Your doctor will regularly evaluate your treatment and decide if you should continue taking nilotinib. If they instruct you to stop taking this medication, they will continue to monitor your CML and, if necessary, may instruct you to restart treatment with nilotinib.

If you have any questions about how nilotinib works or the reason why you or your child has been prescribed this medication, consult with your doctor.

Follow carefully all the instructions of your doctor, even if they are different from the general information contained in this leaflet.

Do not take Nilotinib Stada

If you think you may be allergic, inform your doctor before taking nilotinib .

Warnings and precautions

Consult your doctor or pharmacist before starting to take nilotinib:

• if you have previously experienced cardiovascular events such as a heart attack, chest pain (angina), problems with blood supply to your brain (stroke) or problems with blood flow to your leg (claudication) or if you have risk factors for cardiovascular diseases such as high blood pressure (hypertension), diabetes or problems with lipid levels in your blood (lipid alterations).
• if you have a heart abnormality , such as an abnormal electrical signal called "prolongation of the QT interval".
• if you are receiving medications that lower cholesterol in the blood (statins) or that affect heart rhythm (antiarrhythmics) or the liver (see Other Medications and Nilotinib Stada ).
• if you have a lack of potassium or magnesium.
• if you have a liver or pancreas abnormality.
• if you have symptoms such as easy bruising, fatigue, or shortness of breath or have presented repeated infections.
• if you have undergone a surgical procedure that involved the complete removal of the stomach (total gastrectomy).
• if you have ever had or may have at this time a hepatitis virus infection

B. This is because nilotinib may make hepatitis B active again, which can be fatal in some cases. The doctor should carefully check for signs of this infection before starting treatment.

If any of these cases apply to you or your child, inform your doctor.

During treatment with nilotinib

• if you experience a fainting spell (loss of consciousness) or have an irregular heart rhythm while taking this medication, inform your doctor immediately as this may be a sign of a serious heart problem. Prolongation of the QT interval or irregular heart rhythm can cause sudden death. There have been reports of rare cases of sudden death in patients taking nilotinib.
• if you experience sudden heart palpitations, severe muscle weakness or paralysis, convulsions, or sudden changes in behavior or level of alertness, inform your doctor immediately as this may be a sign of a rapid breakdown of cancer cells called tumor lysis syndrome. There have been reports of rare cases of tumor lysis syndrome in patients treated with nilotinib.
• if you develop chest pain or discomfort, numbness or weakness, walking or speech problems, pain, discoloration, or coldness in a limb, inform your doctor immediately as this may be a sign of a cardiovascular event. There have been reports of serious cardiovascular events including peripheral artery disease, coronary artery disease, and cerebral ischemia in patients taking nilotinib. Your doctor should evaluate your lipid and blood sugar levels before starting treatment with nilotinib and during treatment.
• if you develop swelling of the feet or hands, generalized swelling, or rapid weight gain, inform your doctor as these may be signs of severe fluid retention. There have been reports of rare cases of severe fluid retention in patients treated with nilotinib.

If you are the parents of a child being treated with nilotinib, inform your doctor if any of the conditions described above occur in your child.

Children and adolescents

Nilotinib is used to treat children and adolescents with CML. There is no experience with the use of this medication in children under 2 years of age. There is limited experience in children under 10 years of age with new diagnosis and little experience in children under 6 years of age with patients who did not benefit from previous treatment for CML, including imatinib.

Some children and adolescents being treated with nilotinib may experience slower than normal growth. Your doctor will monitor growth during regular visits.

Other medications and Nilotinib Stada

Nilotinib may interact with other medications.

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. These include, in particular:

• antiarrhythmics – used to treat irregular heart rhythm;
• chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin – medications that may have an undesirable effect on heart electrical activity;
• ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin – used to treat infections;
• ritonavir – a medication in the group of "protease inhibitors" used to treat HIV;
• carbamazepine, phenobarbital, phenytoin – used to treat epilepsy;
• rifampicin – used to treat tuberculosis;
• St. John's Wort – a product derived from plants used to treat depression and other conditions (also known as Hypericum perforatum) ;
• midazolam – used to alleviate anxiety before surgery;
• alfentanil and fentanyl – used to treat pain and as sedatives before or during surgery or medical procedures;
• ciclosporin, sirolimus, and tacrolimus – medications that suppress the body's "self-defense" ability and fight infections and are often used to prevent organ transplant rejection such as the liver, heart, or kidney;
• dihydroergotamine and ergotamine – used to treat dementia;
• lovastatin, simvastatin – used to treat high cholesterol levels in the blood;
• warfarin – used to treat coagulation disorders (such as blood clots or thrombosis);
• astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, or ergot alkaloids (ergotamine, dihydroergotamine).

You should avoid using these medications during treatment with nilotinib. If you are taking any of these medications, your doctor may prescribe alternative medications.

If you are taking statins (a type of medication that lowers cholesterol in the blood), talk to your doctor or pharmacist. If you use nilotinib with certain statins, it may increase the risk of statin-related muscle problems, which in rare cases can lead to severe muscle degeneration (rhabdomyolysis) that can cause kidney damage.

Also, inform your doctor or pharmacist before taking nilotinib if you are taking any antacids, which are medications against stomach acid. These medications should be taken separately from nilotinib:

• H2 blockers, which reduce stomach acid production. H2 blockers should be taken approximately 10 hours before and approximately 2 hours after taking nilotinib;
• antacids such as those containing aluminum hydroxide, magnesium hydroxide, and simethicone, which neutralize high stomach acidity. These antacids should be taken approximately 2 hours before or approximately 2 hours after taking nilotinib.

You should also inform your doctor if you are already taking nilotinib and are prescribed a new medication that you have not taken before during treatment with nilotinib.

Taking Nilotinib Stada with food and drinks

Do not take nilotinib with meals. Food may increase the absorption of nilotinib and therefore increase the amount of nilotinib in the blood, possibly to a dangerous level. Do not drink grapefruit juice or eat grapefruit. It may increase the amount of nilotinib in the blood, probably to a dangerous level.

Pregnancy and breastfeeding

• Nilotinib is not recommended during pregnancy unless it is clearly necessary. If you are pregnant or think you may be, inform your doctor, who will discuss with you whether you can take this medication during pregnancy.
• Women who can become pregnant should use very effective contraception during treatment and for two weeks after completing treatment.
• Nilotinib is not recommended during breastfeeding for two weeks after the last dose. Inform your doctor if you are breastfeeding.

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

If you experience side effects (such as dizziness or vision problems) that may affect your ability to drive safely or use tools or machines after taking this medication, you should avoid these activities until the effect has disappeared.

Nilotinib Stada contains lactose

This medication contains lactose (also known as milk sugar). If your doctor has told you that you have an intolerance to certain sugars, consult with him before taking this medication.

Nilotinib Stada 50 mg and 150 mg contain sodium

This medication contains less than 23 mg of sodium (1 mmol) per dose; that is, it is essentially "sodium-free".

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

How much nilotinib to take

Use in adults

• Newly diagnosed CML patients:The recommended dose is 600 mg per day. The dose is achieved by taking two hard capsules of 150 mg, twice a day.
• CML patients who did not benefit from their previous treatment:The recommended dose is 800 mg per day. This dose is achieved by taking two capsules of 200 mg twice a day.

Use in children and adolescents

• The dose given to your child will depend on their body weight and height. Your doctor will calculate the correct dose to use and will indicate which and how many nilotinib capsules to give to your child. The total daily dose given to your child should not exceed 800 mg.

Your doctor may prescribe a lower dose depending on how you respond to treatment.

Patients aged 65 or older

Nilotinib can be used by patients aged 65 or older at the same dose as the rest of adults.

When to take nilotinib

Take the hard capsules:

• twice a day (approximately every 12 hours);
• at least 2 hours after eating food;
• wait 1 hour before eating again.

Consult your doctor or pharmacist if you have any doubts about when to take this medication. Taking nilotinib every day at the same time will help you remember when to take the hard capsules.

How to take Nilotinib Stada

• Swallow the hard capsules whole with water.
• Do not take any food with the hard capsules.
• Do not open the hard capsules. If you or your child have difficulty swallowing the entire capsule, you should use other medications with nilotinib instead of Nilotinib Stada.

For how long to take Nilotinib Stada

Take nilotinib every day for the time your doctor tells you. This is a long-term treatment. Your doctor will monitor your situation periodically to check that the treatment is having the desired effect.

Your doctor may consider stopping your treatment with nilotinib based on specific criteria. If you have any doubts about how long you should take nilotinib, consult your doctor.

If you take more Nilotinib Stada than you should

If you have taken more nilotinib than you should, or if someone else accidentally takes your hard capsules, contact a doctor or hospital quickly. Show the box of hard capsules and this leaflet. You may need medical treatment.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Nilotinib Stada

If you have forgotten to take a dose, take the next dose at your usual time. Do not take a double dose to compensate for the missed capsule.

If you interrupt treatment with Nilotinib Stada

Do not stop treatment with this medication unless your doctor tells you to. Stopping treatment with nilotinib without your doctor's recommendation puts you at risk of worsening your disease, which could have fatal consequences. Make sure to discuss it with your doctor, nurse, and/or pharmacist if you are thinking of stopping treatment with nilotinib.

If your doctor recommends stopping treatment with Nilotinib Stada

Your doctor will regularly evaluate your treatment with a specific diagnostic test and decide whether you should continue taking this medication. If they tell you to stop nilotinib, they will continue to monitor your CML before, during, and after stopping nilotinib, and if necessary, they may recommend that you restart treatment with nilotinib.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Most side effects are mild to moderate and usually go away within a few days or weeks of treatment.

Some side effects can be serious

Contact your doctor immediately if you notice any of the side effects described.

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

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

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

Unknown frequency of side effects (cannot be estimated from available data):

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor or pharmacist, even if it is a possible adverse reaction that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es.By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

• Maintain this medication out of the sight and reach of children.
• • Do not use this medication after the expiration date that appears on the packaging and in the blister pack after CAD. The expiration date is the last day of the month indicated.
  • This medication does not require special conditions for conservation.
  • Do not use this medication if you observe that the packaging is damaged or shows signs of manipulation.

Medications should not be disposed of through drains or in the trash. Deposit the packaging and medications that you no longer need at the SIGRE collection point at the pharmacy.Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Nilotinib Stada

The other components are:

Content of the hard capsule: lactose monohydrate, crospovidone type A (E1202), anhydrous colloidal silica (E551), magnesium stearate (E470b).

The hard capsule coating: hypromellose (E464), purified water, carrageenan (E407), potassium chloride (E508), erythrosine (E127), yellow iron oxide (E172), red iron oxide (E172), titanium dioxide (E171).

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

See section 2, Nilotinib Stada 50 mg contains lactose and sodium.

The other components are:

Content of the hard capsule: lactose monohydrate, crospovidone type A (E1202), anhydrous colloidal silica (E551), magnesium stearate (E470b).

The hard capsule coating: hypromellose (E464), purified water, carrageenan (E407), potassium chloride (E508), erythrosine (E127), yellow iron oxide (E172), red iron oxide (E172), titanium dioxide (E171).

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

See section 2, Nilotinib Stada 150 mg contains lactose and sodium.

The other components are:

Content of the hard capsule: lactose monohydrate, crospovidone type A (E1202), anhydrous colloidal silica (E551), magnesium stearate (E470b).

The hard capsule coating: hypromellose (E464), purified water, carrageenan (E407), potassium chloride (E508), yellow iron oxide (E172), titanium dioxide (E171).

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

See section 2, Nilotinib Stada 200 mg contains lactose.

Appearance of Nilotinib Stada and packaging contents

Nilotinib 50 mg is presented as hard, opaque capsules (capsules) with a red cap and a yellowish-brown body, size 4 (approximately 14.4 mm long) with the impression in horizontal "50 mg" in black on the body. The hard capsules contain white to yellowish powder.

Nilotinib 150 mg is presented as hard, opaque capsules (capsules) of red color, size 1 (approximately 19.3 mm long) with the impression in horizontal "150 mg" in black on the body. The hard capsules contain white to yellowish powder.

Nilotinib 200 mg is presented as hard, opaque capsules (capsules) of yellowish-brown color, size 0 (approximately 21.4 mm long) with the impression in horizontal "200 mg" in black on the body. The hard capsules contain white to yellowish powder.

Nilotinib 50 mg is packaged in blisters or pre-cut single-dose blisters of PVC/PE/PVdC//Al or OPA/Al/PVC//Al in:

Packaging containing 40 capsules and multiple packaging containing 120 capsules (3 packs of 40).

Packaging containing 40 capsules in single-dose blisters and multiple packaging containing 120 capsules (3 packs of 40) in single-dose blisters.

Nilotinib 150 mg is packaged in blisters or pre-cut single-dose blisters of PVC/PE/PVdC//Al or OPA/Al/PVC//Al in:

Packaging containing 28, 40 capsules and multiple packaging containing 112 (4 packs of 28), 120 (3 packs of 40) and 392 capsules (14 packs of 28).

Packaging containing 28, 40 capsules in single-dose blisters and multiple packaging containing 112 (4 packs of 28), 120 (3 packs of 40) and 392 capsules (14 packs of 28) in single-dose blisters.

Nilotinib 200 mg is packaged in blisters or pre-cut single-dose blisters of PVC/PE/PVdC//Al or OPA/Al/PVC//Al in:

Packaging containing 28, 40 capsules and multiple packaging containing 112 (4 packs of 28), 120 (3 packs of 40) and 392 capsules (14 packs of 28).

Packaging containing 28, 40 capsules in single-dose blisters and multiple packaging containing 112 (4 packs of 28), 120 (3 packs of 40) and 392 capsules (14 packs of 28) in single-dose blisters.

Only some packaging sizes may be commercially available.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

Laboratorio STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Responsible manufacturer

PharOS Pharmaceutical Oriented Services Ltd.

Lesvou Street End, Thesi Loggos Industrial Zone,

Metamorfossi, 144 52,

Greece

or

STADA Arzneimittel AG

Stadastrasse 2 – 18, 61118 Bad Vilbel

Germany

or

Clonmel Healthcare Ltd.

Waterford Road, Clonmel, Co. Tipperary,

Ireland

or

STADA Arzneimittel GmbH

Muthgasse 36/2, 1190 Wien

Austria

This medicinal product is authorized in the Member States of the European Economic Area with the following names:

Austria: Nilotinib STADA 50 mg Hartkapseln

Nilotinib STADA 150 mg Hartkapseln

Nilotinib STADA 200 mg Hartkapseln

Belgium: Nilotinib EG 50 mg harde capsules

Nilotinib EG 150 mg harde capsules

Nilotinib EG 200 mg harde capsules

Cyprus: Nilotinib Stada 50mg σκληρ? καψ?κιο

Nilotinib Stada 150mg σκληρ? καψ?κιο

Nilotinib Stada 200mg σκληρ? καψ?κιο

Czech Republic: Nilotinib STADA

Germany: Nilotinib AL 50 mg Hartkapseln

Nilotinib AL 150 mg Hartkapseln

Nilotinib AL 200 mg Hartkapseln

Denmark: Nilotinib STADA

Estonia: Nilotinib STADA

Greece: Nilotinib Stada

Spain: Nilotinib STADA 50 mg cápsulas duras EFG

Nilotinib STADA 150 mg cápsulas duras EFG

Nilotinib STADA 200 mg cápsulas duras EFG

Finland: Nilotinib STADA 50 mg kapseli, kova

Nilotinib STADA 150 mg kapseli, kova

Nilotinib STADA 200 mg kapseli, kova

France: NILOTINIB EG 50 mg, gélule

NILOTINIB EG 150 mg, gélule

NILOTINIB EG 200 mg, gélule

Croatia: Nilotinib STADA 50 mg tvrde kapsule

Nilotinib STADA 150 mg tvrde kapsule

Nilotinib STADA 200 mg tvrde kapsule

Hungary: Nilotinib STADA 50 mg kemény kapszula

Nilotinib STADA 150 mg kemény kapszula

Nilotinib STADA 200 mg kemény kapszula

Ireland: Nilotinib Clonmel 50 mg hard capsules

Nilotinib Clonmel 150 mg hard capsules

Nilotinib Clonmel 200 mg hard capsules

Iceland: Nilotinib STADA 50 mg hörð hylki

Nilotinib STADA 150 mg hörð hylki

Nilotinib STADA 200 mg hörð hylki

Italy: NILOTINIB EG

Lithuania: Nilotinib STADA 50 mg kietosios kapsules

Nilotinib STADA 100 mg kietosios kapsules

Nilotinib STADA 200 mg kietosios kapsules

Luxembourg: Nilotinib EG 50 mg gélules

Nilotinib EG 150 mg gélules

Nilotinib EG 200 mg gélules

Latvia: Nilotinib STADA 50 mg cietas kapsulas

Nilotinib STADA 100 mg cietas kapsulas

Nilotinib STADA 200 mg cietas kapsulas

Malta: Nilotinib Clonmel 50 mg hard capsules

Nilotinib Clonmel 150 mg hard capsules

Nilotinib Clonmel 200 mg hard capsules

Netherlands: Nilotinib CF 50 mg, harde capsules

Nilotinib CF 150 mg, harde capsules

Nilotinib CF 200 mg, harde capsules

Norway: Nilotinib STADA

Poland: Nilotinib STADA

Portugal: Nilotinib Stada

Romania: Nilotinib Stada 50 mg capsule

Nilotinib Stada 150 mg capsule

Nilotinib Stada 200 mg capsule

Sweden: Nilotinib STADA

Slovenia: Nilotinib STADA 50 mg trde kapsule

Nilotinib STADA 150 mg trde kapsule

Nilotinib STADA 200 mg trde kapsule

Slovakia: Nilotinib STADA 50 mg tvrdé kapsuly

Nilotinib STADA 150 mg tvrdé kapsuly

Nilotinib STADA 200 mg tvrdé kapsuly

Last date of revision of this leaflet: May 2024

Other sources of information

You can access the approved leaflet of this medicinal product by scanning with your smartphone (smartphone) the QR code included in the outer packaging. You can also access this information on the following internet address: https://cima.aemps.es/cima/dochtml/p/XXXXX/P_XXXXX.html

The detailed information of this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/