Nilotinib 150 mg Hard Capsules

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

Nilotinib is a medicine containing an active substance called nilotinib.

Nilotinib is used to treat a type of leukaemia called Philadelphia chromosome positive chronic myeloid leukaemia (Ph-positive CML). CML is a cancer of the blood which makes the body produce too many abnormal white blood cells.

Nilotinib is used in adult and paediatric patients with newly diagnosed CML or in patients with CML who are no longer benefiting from previous treatment including imatinib. It is also used in adult and paediatric patients who experienced serious side effects with previous treatment and are not able to continue taking it.

In patients with CML, a change in DNA (genetic material) triggers a signal that tells the body to produce abnormal white blood cells.

Nilotinib blocks this signal, and thus stops the production of these cells.

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

• the amount of blood cells (white blood cells, red blood cells and platelets) in the body to see how Nilotinib is tolerated.
• pancreas and liver function in the body to see how Nilotinib is tolerated.
• the electrolytes in the body (potassium, magnesium). These are important in the functioning of the heart.
• the level of sugar and fats in the blood.
• the heart rate will also be checked using a machine that measures electrical activity of the heart (a test called an “ECG”).

Your doctor will regularly evaluate your treatment and decide whether you should continue to take Nilotinib. If you are told to discontinue this medicine, your doctor will continue to monitor your CML and may tell you to re-start Nilotinib if your condition indicates that this is necessary.

If you have any questions about how Nilotinib works or why it has been prescribed for you or your child, ask your doctor.

• if you are allergic to nilotinib or any of the other ingredients of this medicine (listed in section 6).

If you think you may be allergic, tell your doctor before taking Nilotinib.

Talk to your doctor or pharmacist before taking Nilotinib if you:

• have suffered prior cardiovascular events such as a heart attack, chest pain (angina), problems with the blood supply to your brain (stroke) or problems with the blood flow to your leg (claudication) or if you have risk factors for cardiovascular disease such as high blood pressure (hypertension), diabetes or problems with the level of fats in your blood (lipid disorders).
• have a heart disorder, such as an abnormal electrical signal called “prolongation of the QT interval”.
• are being treated with medicines that lower your blood cholesterol (statins), or affect the heartbeat (anti-arrhythmics) or the liver (see Other medicines and Nilotinib).
• suffer from lack of potassium or magnesium.
• have a liver or pancreas disorder.
• have symptoms such as easy bruising, feeling tired or short of breath or have experienced repeated infections.
• have had a surgical procedure involving the removal of the entire stomach (total gastrectomy).
• have ever had or might now have a hepatitis B infection. This is because Nilotinib could cause hepatitis B to become active again, which can be fatal in some cases. Patients will be carefully checked by their doctor for signs of this infection before treatment is started.

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

During treatment with Nilotinib

• if you faint (loss of consciousness) or have an irregular heart beat while taking this medicine, tell your doctor immediately as this may be a sign of a serious heart condition. Prolongation of the QT interval or an irregular heart beat may lead to sudden death. Uncommon cases of sudden death have been reported in patients taking nilotinib.
• if you have sudden heart palpitations, severe muscle weakness or paralysis, seizures or sudden changes in your thinking or level of alertness, tell your doctor immediately as this may be a sign of a fast breakdown of cancer cells called tumour lysis syndrome. Rare cases of tumour lysis syndrome have been reported in patients treated with nilotinib.
• if you develop chest pain or discomfort, numbness or weakness, problems with walking or with your speech, pain, discolouration or a cool feeling in a limb, tell your doctor immediately as this may be a sign of a cardiovascular event. Serious cardiovascular events including problems with the blood flow to the leg (peripheral arterial occlusive disease), ischaemic heart disease and problems with the blood supply to the brain (ischaemic cerebrovascular disease) have been reported in patients taking nilotinib. Your doctor should assess the level of fats (lipids) and sugar in your blood before initiating treatment with nilotinib and during treatment.
• if you develop swelling of the feet or hands, generalised swelling or rapid weight gain tell your doctor as these may be signs of severe fluid retention. Uncommon cases of severe fluid retention have been reported in patients treated with nilotinib.

If you are the parent of a child who is being treated with Nilotinib, tell the doctor if any of the above conditions apply to your child.

Nilotinib is a treatment for children and adolescents with CML. There is no experience with the use of this medicine in children below 2 years of age. There is no experience with the use of Nilotinib in newly diagnosed children below 10 years of age and limited experience in patients below 6 years of age who are no longer benefiting from previous treatment for CML.

Some children and adolescents taking nilotinib may have slower than normal growth. The doctor will monitor growth at regular visits.

Nilotinib may interfere with some other medicines.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes in particular:

• anti-arrhythmics - used to treat irregular heart beat;
• chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin - medicines that may have an unwanted effect on the electrical activity of the heart;
• ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin – used to treat infections;
• ritonavir – a medicine from the class “antiproteases” used to treat HIV;
• carbamazepine, phenobarbital, phenytoin – used to treat epilepsy;
• rifampicin – used to treat tuberculosis;
• St. John’s Wort – a herbal product used to treat depression and other conditions (also known as Hypericum perforatum);
• midazolam – used to relieve anxiety before surgery;
• alfentanil and fentanyl – used to treat pain and as a sedative before or during surgery or medical procedures;
• ciclosporin, sirolimus and tacrolimus – medicines that suppress the “self-defence” ability of the body and fight infections and are commonly used to prevent the rejection of transplanted organs such as the liver, heart and kidney;
• dihydroergotamine and ergotamine – used to treat dementia;
• lovastatin, simvastatin – used to treat high level of fats in blood;
• warfarin – used to treat blood coagulation disorders (such as blood clots or thromboses);
• astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil or ergot alkaloids (ergotamine, dihydroergotamine).

These medicines should be avoided during your treatment with nilotinib. If you are taking any of these, your doctor might prescribe other alternative medicines.

If you are taking a statin (a type of medicine to lower your blood cholesterol), talk to your doctor or pharmacist. If used with certain statins, nilotinib may increase the risk of statin-related muscle problems, which on rare occasions can lead to serious muscle breakdown (rhabdomyolysis) resulting in kidney damage.

In addition, tell your doctor or pharmacist before taking nilotinib if you are taking any antacids, which are medicines against heartburn. These medicines need to be taken separately from nilotinib:

• H2 blockers, which decrease the production of acid in the stomach. H2 blockers should be taken approximately 10 hours before and approximately 2 hours after you take Nilotinib;
• antacids such as those containing aluminium hydroxide, magnesium hydroxide and simethicone, which neutralise high acidity in the stomach. These antacids should be taken approximately 2 hours before or approximately 2 hours after you take Nilotinib.

You should also tell your doctor if you are already taking nilotinib and you are prescribed a new medicine that you have not taken previously during nilotinib treatment.

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

• Nilotinib is not recommended during pregnancy unless clearly necessary. If you are pregnant or think that you may be, tell your doctor who will discuss with you whether you can take this medicine during your pregnancy.
• Women who might get pregnant are advised to use highly effective contraception during treatment and for up to two weeks after ending treatment.
• Breast-feeding is not recommended during treatment with nilotinib and for two weeks after the last dose. Tell your doctor if you are breast-feeding.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

If you experience side effects (such as dizziness or visual disorders) with a potential impact on the ability to safely drive or use any tools or machines after taking this medicine, you should refrain from these activities until the effect has disappeared.

This medicine contains lactose (also known as a milk sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially sodium free.

Use in adults

• Patients newly diagnosed with CML: The recommended dose is 600 mg per day. This dose is achieved by taking two hard capsules of 150 mg twice a day.
• Patients who are no longer benefiting from previous treatment for CML: The recommended dose is 800 mg per day. This dose is achieved by taking two hard capsules of 200 mg twice a day.

Use in children and adolescents

• The dose given to your child will depend on your child’s body weight and height. The doctor will calculate the correct dose to use and tell you which and how many capsules of Nilotinib to give to your child. The total daily dose you give to your child must not exceed 800 mg.

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

Nilotinib can be used by people aged 65 years and over at the same dose as for other adults.

Take the hard capsules:

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

If you have questions about when to take this medicine, talk to your doctor or pharmacist. Taking Nilotinib at the same time each day will help you remember when to take your hard capsules.

• Swallow the hard capsules whole with water.
• Do not take any food together with the hard capsules.
• Do not open the hard capsules. If you or your child are not able to swallow the whole capsule, other medicines with nilotinib should be used instead of Nilotinib hard capsules.

Continue taking Nilotinib every day for as long as your doctor tells you. This is a long-term treatment. Your doctor will regularly monitor your condition to check that the treatment is having the desired effect.

Your doctor may consider discontinuing your treatment with Nilotinib based on specific criteria.

If you have questions about how long to take Nilotinib talk to your doctor.

If you have taken more Nilotinib than you should have, or if someone else accidentally takes your hard capsules, contact a doctor or hospital for advice straight away. Show them the pack of hard capsules and this package leaflet. Medical treatment may be necessary.

If you miss a dose, take your next dose as scheduled. Do not take a double dose to make up for a forgotten hard capsule.

Do not stop taking this medicine unless your doctor tells you to do so. Stopping Nilotinib without your doctor’s recommendation places you at risk for worsening of your disease which could have life-threatening consequences. Be sure to discuss with your doctor, nurse, and/or pharmacist if you are considering stopping Nilotinib.

Your doctor will regularly evaluate your treatment with a specific diagnostic test and decide whether you should continue to take this medicine. If you are told to discontinue Nilotinib your doctor will continue to carefully monitor your CML before, during and after you have discontinued Nilotinib and may tell you to re-start Nilotinib if your condition indicates that this is necessary.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the MHRA Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

• The active substance is nilotinib.
  • Each 150 mg hard capsule contains 150 mg nilotinib.
  • Each 200 mg hard capsule contains 200 mg nilotinib.
• The other ingredients are:

Capsule content:

• Lactose monohydrate, crospovidone (E1202), polysorbate 80, magnesium aluminometasilicate, colloidal silicon dioxide (E551), magnesium stearate (E572).

Capsule shell:

• Gelatin (E441), titanium dioxide (E171), iron oxide yellow (E172).
• The 150 mg capsule shells also contains iron oxide red (E172).

Printing ink:

• The printing ink on the 150 mg capsules contains, shellac (E904), black iron oxide (E172), potassium hydroxide (E525).
• The printing ink on the 200 mg capsules contains, shellac (E904), sodium hydroxide (E524), titanium dioxide (E171), povidone (E1201), Allura red AC aluminium lake (E129).

Nilotinib 150 mg: - Hard gelatin capsule with red opaque cap and red opaque body imprinted with black ink “SML” on the cap and “26” on the body containing off white to grey granular powder.

Nilotinib 200 mg: - Hard gelatin capsule with light yellow opaque cap and light yellow opaque body imprinted with red ink “SML” on the cap and “27” on the body containing off white to grey granular powder.

The capsules are packed in PVC/PVDC/Alu blisters or perforated unit dose blisters

Pack sizes:

28 hard capsules in blisters.

28x1 hard capsules in perforated unit dose blisters.

Multipack containing 112 (4 packs of 28) or 392 (14 packs of 28) hard capsules in blisters.

Multipack containing 112x1 (4 packs of 28x1) or 392x1 (14 packs of 28x1) hard capsules in perforated unit dose blisters.

Not all pack sizes may be marketed.

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