Tasigna - patient leaflet, side effects, dosage

1. What Tasigna is and what it is used for

What Tasigna is

Tasigna is a medicine containing an active substance called nilotinib.

What Tasigna is used for

Tasigna 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.

Tasigna 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.

How Tasigna works

In patients with CML, a change in DNA (genetic material) triggers a signal that tells the body to produce abnormal white blood cells. Tasigna blocks this signal, and thus stops the production of these cells.

Monitoring during Tasigna treatment

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 Tasigna is tolerated.

• – pancreas and liver function in the body to see how Tasigna 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 Tasigna. If you are told to discontinue this medicine, your doctor will continue to monitor your CML and may tell you to re-start Tasigna if your condition indicates that this is necessary.

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

2. What you need to know before you take Tasigna

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

Do not take Tasigna

• – 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 Tasigna.

Warnings and precautions

Talk to your doctor or pharmacist before taking Tasigna:

• – 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).

• – if you have a heart disorder , such as an abnormal electrical signal called “prolongation of the

QT interval”.

• – if you are being treated with medicines that lower your blood cholesterol (statins), or affect the

heart beat (anti-arrhythmics) or the liver (see Other medicines and Tasigna ).

• – if you suffer from lack of potassium or magnesium.

• – if you have a liver or pancreas disorder.

• – if you have symptoms such as easy bruising, feeling tired or short of breath or have experienced

repeated infections.

• – if you have had a surgical procedure involving the removal of the entire stomach (total

gastrectomy).

• – if you have ever had or might now have a hepatitis B infection. This is because Tasigna 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 Tasigna

• – 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 Tasigna.

• – 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 Tasigna.

• – 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 Tasigna. Your doctor should assess the level of fats (lipids) and sugar in your blood before initiating treatment with Tasigna 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 Tasigna.

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

Children and adolescents

Tasigna 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 Tasigna 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 Tasigna may have slower than normal growth. The doctor will monitor growth at regular visits.

Other medicines and Tasigna

Tasigna 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;

• – cyclosporine, 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 Tasigna. 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, Tasigna 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 Tasigna if you are taking any antacids, which are medicines against heartburn. These medicines need to be taken separately from Tasigna:

• – 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 Tasigna;

• – 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 Tasigna.

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

Tasigna with food and drink

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

Pregnancy and breast-feeding

• - Tasigna 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 Tasigna 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.

Driving and using machines

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.

Tasigna contains lactose

This medicine contains lactose (also known as 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.

3. How to take Tasigna

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

How much Tasigna to take

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 Tasigna 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.

Older people (age 65 years and over)

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

When to take Tasigna

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 Tasigna at the same time each day will help you remember when to take your hard capsules.

How to take Tasigna

• – Swallow the hard capsules whole with water.

• – Do not take any food together with the hard capsules.

• – Do not open the hard capsules unless you are unable to swallow them. If so, you may sprinkle

the content of each hard capsule in one teaspoon of apple sauce and take it immediately. Do not use more than one teaspoon of apple sauce for each hard capsule and do not use any food other than apple sauce.

How long to take Tasigna

Continue taking Tasigna 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 Tasigna based on specific criteria.

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

If you take more Tasigna than you should

If you have taken more Tasigna 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 forget to take Tasigna

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.

If you stop taking Tasigna

Do not stop taking this medicine unless your doctor tells you to do so. Stopping Tasigna 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 Tasigna.

If your doctor recommends that you discontinue treatment with Tasigna

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 Tasigna, your doctor will continue to carefully monitor your CML before, during and after you have discontinued Tasigna and may tell you to re-start Tasigna if your condition indicates that this is necessary.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most of the side effects are mild to moderate and will generally disappear after a few days to a few weeks of treatment.

Some side effects could be serious.

These side effects are very common (may affect more than 1 in 10 people), common (may affect up to 1 in 10 people), uncommon (may affect up to 1 in 100 people) or have been reported with frequency not known (cannot be estimated from the available data).

• – rapid weight gain, swelling of hands, ankles, feet or face (signs of water retention)

• – chest pain or discomfort, high or low blood pressure, irregular heart rhythm (fast or slow),

palpitations (sensation of rapid heartbeat), fainting, blue discolouration of the lips, tongue or skin (signs of heart disorders)

• – difficulty breathing or painful breathing, cough, wheezing with or without fever, swelling of the

feet or legs (signs of lung disorders)

• – fever, easy bruising or unexplained bleeding, severe or frequent infections, unexplained

weakness (signs of blood disorders)

• – weakness or paralysis of the limbs or face, difficulty speaking, severe headache, seeing, feeling

or hearing things that are not there, changes in eyesight, loss of consciousness, confusion, disorientation, trembling, sensation of tingling, pain or numbness in fingers and toes (signs of nervous system disorders)

• – thirst, dry skin, irritability, dark urine, decreased urine output, difficulty and pain when

urinating, exaggerated sense of needing to urinate, blood in urine, abnormal urine colour (signs of kidney or urinary tract disorders)

• – visual disturbances including blurred vision, double-vision or perceived flashes of light,

decreased sharpness or loss of vision, blood in eye, increased sensitivity of the eyes to light, eye pain, redness, itching or irritation, dry eye, swelling or itching of the eyelids (signs of eye disorders)

• – swelling and pain in one part of the body (signs of clotting within a vein)

• – abdominal pain, nausea, vomiting of blood, black or bloody stools, constipation, heartburn,

stomach acid reflux, swollen abdomen (signs of gastrointestinal disorders)

• – severe upper (middle or left) abdominal pain (sign of pancreatitis)

• – yellow skin and eyes, nausea, loss of appetite, dark-coloured urine (signs of liver disorders)

• – painful red lumps, skin pain, skin reddening, peeling or blisters (signs of skin disorders)

• – pain in joints and muscles (signs of musculoskeletal pa­in)

• – excessive thirst, high urine output, increased appetite with weight loss, tiredness (signs of high

level of sugar in the blood)

• – fast heartbeat, bulging eyes, weight loss, swelling at the front of the neck (signs of overactive

thyroid gland)

• – weight gain, tiredness, hair loss, muscle weakness, feeling cold (signs of underactive thyroid

gland)

• – severe headache often accompanied by nausea, vomiting and sensitivity to light (signs of

migraine)

• – dizziness or spinning sensation (signs of vertigo)

• – nausea, shortness of breath, irregular heartbeat, clouding of urine, tiredness and/or joint

discomfort associated with abnormal results of blood tests (such as high levels of potassium, uric acid and phosphorous and low levels of calcium)

• – pain, discomfort, weakness or cramping in the leg muscles, which may be due to decreased

blood flow, ulcers on the legs or arms that heal slowly or not at all and noticeable changes in colour (blueness or paleness) or temperature (coolness) of the legs or arms, as these symptoms could be signs of artery blockage in the affected limb (leg or arm) and digits (toes or fingers)

• – recurrence (reactivation) of hepatitis B infection when you have had hepatitis B in the past (a

liver infection).

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

• – diarrhoea

• – headache

• – tiredness, lack of energy

• – muscle pain

• – itching, rash

• – nausea

• – abdominal pain

• – constipation

• – vomiting

• – hair loss

• – musculoskeletal pain, muscle pain, pain in extremity, pain in joints, bone pain and spinal pain

upon discontinuing treatment with Tasigna

• – slowing of growth in children and adolescents

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

• – upper respiratory tract infections, pneumonia

• – stomach discomfort after meals, flatulence, swelling or bloating of the abdomen

• – bone pain, pain in joints, muscle spasms, muscle weakness

• – pain including back pain, neck pain and pain in extremity, pain or discomfort in the side of the

body

• – dry skin, acne, wart, decreased skin sensitivity, hives

• – loss of appetite, disturbed sense of taste, weight decrease or increase

• – insomnia, depression, anxiety

• – night sweats, excessive sweating

• – generally feeling unwell

• – voice disorder

• – nose bleed

• – frequent urine output

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

• – increased skin sensitivity

• – dry mouth, sore throat, mouth sores

• – breast pain

• – painful and swollen joints (gout)

• – increased appetite

• – attention disorder

• – inability to achieve or maintain an erection

• – breast enlargement in men

• – flu-like symptoms

• – bronchitis

• – urinary tract infection

• – herpes virus infection

• – oral or vaginal thrush

• – muscle and joint stiffness, joint swelling

• – feeling body temperature change (including feeling hot, feeling cold)

• – sensitive teeth

The following other side effects have been reported with frequency not known (cannot be estimated from the available data):

• – allergy (hypersensitivity to Tasigna)

• – memory loss, disturbed mood

• – skin cyst, thinning or thickening of the skin, thickening of the outermost layer of the skin, skin

discolouration, fungal infection of the feet

• – thickened patches of red/silver skin (signs of psoriasis)

• – bleeding, tender or enlarged gums

• – oral warts

• – reddening and/or swelling and possibly peeling on the palms and soles (so called hand-foot

syndrome)

• – increased sensitivity of the skin to light

• – difficulty hearing, ear pain, noises (ringing) in the ears

• – joint inflammation

• – urinary incontinence

• – enterocolitis (inflammation of the bowel)

• – haemorrhoids, anal abscess

• – feeling of hardening in the breasts, heavy periods, nipple swelling

• – symptoms of restless legs syndrome (an irresistable urge to move a part of the body, usually the

leg, accompanied by uncomfortable sensations)

• – paralysis of any muscle of the face

During Tasigna treatment, you may also have some abnormal blood test results such as:

• – low level of blood cells (white cells, red cells, platelets) or haemoglobin

• – increase in the number of platelets or white cells, or specific types of white cells (eosinophils) in

the blood

• – high blood level of lipase or amylase (pancreas function)

• – high blood level of bilirubin or liver enzymes (liver function)

• – high blood level of creatinine or urea (kidney function)

• – low or high blood level of insulin (a hormone regulating blood sugar level)

• – low or high level of sugar, or high level of fats (including cholesterol) in the blood

• – high blood level of parathyroid hormone (a hormone regulating calcium and phosphorus level)

• – change in blood proteins (low level of globulins or presence of paraprotein)

• – high blood levels of enzymes (alkaline phosphatase, lactate dehydrogenase or creatine

phosphokinase)

• – high blood level of potassium, calcium, phosphorus or uric acid

• – low blood level of magnesium, potassium, sodium, calcium, or phosphorus

Reporting of side effects

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 national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Tasigna

• – Keep this medicine out of the sight and reach of children.

• – Do not use this medicine after the expiry date which is stated on the carton and blister. The

expiry date refers to the last day of that month.

• – Do not store above 30°C.

• – Store in the original package in order to protect from moisture.

• – Do not use this medicine if you notice that the pack is damaged or shows signs of tampering.

• – Do not throw away any medicines via wastewater or household waste. Ask your pharmacist

how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Tasigna contains

• – The active substance is nilotinib. Each hard capsule contains 50 mg nilotinib (as hydrochloride

monohydrate).

• – The other ingredients are lactose monohydrate, crospovidone type A, poloxamer 188, colloidal

What Tasigna looks like and contents of the pack

Tasigna is supplied as hard capsules. The hard capsules are red/light yellow. A black imprint is stamped on each hard capsule (“NVR/ABL”).

Tasigna is available in a pack containing 120 hard capsules (3 packs of 40 hard capsules).

Marketing Authorisation Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Manufacturer

Novartis Farmacéutica SA

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Novartis Pharma GmbH

RoonstraBe 25

D-90429 Nuremberg

Germany

Lek d.d., PE PROIZVODNJA LENDAVA

Trimlini 2D

Lendava, 9220

Slovenia

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgiqu­e/Belgien Novartis Pharma N.V. Tél/Tel: +32 2 246 16 11	Lietuva SIA Novartis Baltics Lietuvos filialas Tel: +370 5 269 16 50
E’b.nrapufl	Luxembourg/Lu­xemburg
Novartis Bulgaria EOOD	Novartis Pharma N.V.
Tea.: +359 2 489 98 28	Tél/Tel: +32 2 246 16 11
Česká republika	Magyarorszag
Novartis s.r.o.	Novartis Hungaria Kft.
Tel: +420 225 775 111	Tel.: +36 1 457 65 00

Danmark Novartis Healthcare A/S Tlf: +45 39 16 84 00	Malta Novartis Pharma Services Inc. Tel: +356 2122 2872
Deutschland Novartis Pharma GmbH Tel: +49 911 273 0	Nederland Novartis Pharma B.V. Tel: +31 88 04 52 555
Eesti SIA Novartis Baltics Eesti filiaal Tel: +372 66 30 810	Norge Novartis Norge AS Tlf: +47 23 05 20 00
EMàôa Novartis (Hellas) A.E.B.E. Tqk +30 210 281 17 12	Österreich Novartis Pharma GmbH Tel: +43 1 86 6570
España Novartis Farmacéutica, S.A. Tel: +34 93 306 42 00	Polska Novartis Poland Sp. z o.o. Tel.: +48 22 375 4888
France Novartis Pharma S.A.S. Tél: +33 1 55 47 66 00	Portugal Novartis Farma – Produtos Farmacêuticos, S.A. Tel: +351 21 000 8600
Hrvatska Novartis Hrvatska d.o.o. Tel. +385 1 6274 220	România Novartis Pharma Services Romania SRL Tel: +40 21 31299 01
Ireland Novartis Ireland Limited Tel: +353 1 260 12 55	Slovenija Novartis Pharma Services Inc. Tel: +386 1 300 75 50
Ísland Vistor hf. Sími: +354 535 7000	Slovenská republika Novartis Slovakia s.r.o. Tel: +421 2 5542 5439
Italia Novartis Farma S.p.A. Tel: +39 02 96 54 1	Suomi/Finland Novartis Finland Oy Puh/Tel: +358 (0)10 6133 200
Kúnpog Novartis Pharma Services Inc. Tqk +357 22 690 690	Sverige Novartis Sverige AB Tel: +46 8 732 32 00
Latvija SIA Novartis Baltics Tel: +371 67 887 070	United Kingdom (Northern Ireland) Novartis Ireland Limited Tel: +44 1276 698370

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:. There are also links to other websites about rare diseases and treatments.