SPRYCEL 100 mg FILM-COATED TABLETS

Introduction

Patient Information: Summary of Product Characteristics

SPRYCEL20mg film-coated tablets

SPRYCEL50mg film-coated tablets

SPRYCEL70mg film-coated tablets

SPRYCEL80mg film-coated tablets

SPRYCEL100mg film-coated tablets

SPRYCEL140mg film-coated tablets

dasatinib

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

• 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.

Contents of the pack and other information

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

1. What SPRYCEL is and what it is used for

SPRYCEL contains the active substance dasatinib. This medicine is used to treat chronic myeloid leukaemia (CML) in adults, adolescents, and children aged 1 year and above. Leukaemia is a type of cancer that affects the white blood cells. These white blood cells usually help the body fight infection. In patients with CML, a type of white blood cell called granulocytes start to multiply out of control. SPRYCEL inhibits the growth of these leukaemic cells.

SPRYCEL is also used to treat Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) in adults, adolescents, and children aged 1 year and above, and lymphoid blast crisis CML in adults who have not benefited from previous treatments. In patients with Ph+ ALL, a type of white blood cell called lymphocytes multiply too quickly and live too long. SPRYCEL inhibits the growth of these leukaemic cells.

If you have any questions about how SPRYCEL works or why you have been prescribed this medicine, ask your doctor.

2. What you need to know before you take SPRYCEL

Do not take SPRYCEL

• if you are allergicto dasatinib or any of the other ingredients of this medicine (listed in section 6).

If you think you may be allergic, consult your doctor.

Warnings and precautions

Consult your doctor or pharmacist before taking SPRYCEL

• if you are taking medicines to thin your bloodor prevent blood clots (see Taking other medicines with SPRYCEL)
• if you have or have had any liver or heart problems
• if you start having difficulty breathing, chest pain, or coughwhile taking SPRYCEL: this may be a sign of fluid build-up in the lungs or chest (which may be more common in patients 65 years or older) or due to changes in the blood vessels that supply blood to the lungs
• if you have ever had or may currently have a hepatitis B virus infection. This is because SPRYCEL could cause the hepatitis B virus to become active again, which can be fatal in some cases. Your doctor will carefully check for signs of this infection before starting treatment.
• If you experience bruising, bleeding, fever, fatigue, and confusion while taking SPRYCEL, contact your doctor. This may be a sign of blood vessel damage known as thrombotic microangiopathy (TMA).

Your doctor will regularly check your condition to see if SPRYCEL is having the desired effect. You will also have regular blood tests while taking SPRYCEL.

Children and adolescents

Do not give this medicine to children under 1 year of age. Experience with the use of SPRYCEL in this age group is limited. In children taking SPRYCEL, growth and bone development should be closely monitored.

Other medicines and SPRYCEL

Tell your doctor or pharmacistif you are taking, have recently taken, or might take any other medicines.

SPRYCEL is mainly broken down in the liver. Some medicines may interfere with the effect of SPRYCEL when taken together.

The following medicines must not be used during treatment with SPRYCEL:

• ketoconazole, itraconazole – medicines for fungal infections
• erythromycin, clarithromycin, telithromycin – antibiotics
• ritonavir – an antiviral medicine
• phenytoin, carbamazepine, phenobarbital – treatments for epilepsy
• rifampicin – a treatment for tuberculosis
• famotidine, omeprazole – medicines that block stomach acid production
• St. John's Wort - a herbal medicine that can be bought without a prescription for the treatment of depressionand other conditions (also known as Hypericum perforatum)

Do not takemedicines that neutralize stomach acid (antacidssuch as aluminium hydroxide/magnesium hydroxide) in the 2hours before or 2hours after taking SPRYCEL.

Tell your doctorif you are taking medicines to thin your bloodor prevent blood clots.

Taking SPRYCEL with food and drinks

Do not take SPRYCEL with grapefruit or grapefruit juice.

Pregnancy and breastfeeding

If you are pregnantor think you may be pregnant, tell your doctor immediately. SPRYCEL must not be used during pregnancyunless clearly necessary. Your doctor will inform you of the potential risk of taking SPRYCEL during pregnancy.

Both men and women are advised to use effective contraceptive methods during treatment with SPRYCEL.

If you are breastfeeding, tell your doctor.You must stop breastfeeding while taking SPRYCEL.

Driving and using machines

Be careful when driving or using machines if you experience side effects such as dizziness or blurred vision.

SPRYCEL contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take SPRYCEL

SPRYCEL will only be prescribed by a doctor with experience in treating leukaemia. Follow the instructions for taking this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist again. SPRYCEL is prescribed for adults and children aged 1 year and above.

The recommended starting dose for adult patients with CML in the chronic phase is 100mg once daily.

The recommended starting dose for adult patients with CML in the accelerated phase or blast crisis or Ph+ ALL is 140mg once daily.

Dosing regimen in children with CML in the chronic phase or Ph+ ALL based on body weightSPRYCEL is given orally once daily, either as tablets or as a powder for oral suspension. SPRYCEL tablets are not recommended in patients who weigh less than 10 kg. The powder for oral suspension should be used in patients who weigh less than 10 kg and in patients who cannot swallow tablets. A dose change may be required when switching between formulations (i.e., tablets and powder for oral suspension), so do not switch between formulations.

Your doctor will decide on the correct formulation and dose based on your weight, side effects, and response to treatment. In children, the starting dose of SPRYCEL is calculated according to body weight as shown below:

a SPRYCEL tablets are not recommended in patients who weigh less than 10 kg; the powder for oral suspension should be used in these patients.

There is no recommended dose for SPRYCEL in children under 1 year of age.

Depending on how you respond to treatment, your doctor may prescribe a higher or lower dose, or even interrupt treatment briefly. To take higher or lower doses, you may need to take combinations of tablets of different strengths.

SPRYCEL tablets may be presented in calendar blister packs.These are blisters that show the days of the week. The arrows indicate the next tablet to be taken according to your treatment schedule.

How to take SPRYCEL

Take the tablets at the same time each day.Swallow the tablets whole. Do not crush, cut, or chew them. Do not take the tablets dissolved. You cannot be sure you are getting the correct dose if you crush, cut, chew, or dissolve the tablets. SPRYCEL tablets can be taken with or without food.

Special handling instructions for SPRYCEL

It is unlikely that SPRYCEL tablets will break, but if they do, people other than the patient should wear gloves when handling SPRYCEL.

How long to take SPRYCEL

Take SPRYCEL daily until your doctor tells you to stop. Make sure you take SPRYCEL for the duration your doctor has prescribed.

If you take more SPRYCEL than you should

If you accidentally take too many tablets, contact your doctor immediately. You may need medical attention.

If you forget to take SPRYCEL

Do not take a double dose to make up for forgotten doses. Take the next dose at the usual time.

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

4. Possible Adverse Effects

• Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

The following may be signs of serious adverse effects:

unexpected bleeding or bruisingwithout injuryinfection symptoms, such as fever, severe chills

Contact your doctor immediatelyif you notice any of the above.

Very common adverse effects (may affect more than 1 in 10 patients)

• Infections(caused by bacteria, viruses, and fungi)
• Heart and lungs: difficulty breathing
• Digestive problems: diarrhea, feeling unwell (nausea, vomiting)
• Skin, hair, eyes, general: skin rash, fever, swelling in the face, hands, and feet, headache, fatigue or weakness, bleeding
• Pain: muscle pain (during or after stopping treatment), abdominal pain
• Laboratory tests: low platelet count, low white blood cell count (neutropenia), anemia, fluid around the lungs

Common adverse effects (may affect up to 1 in 10 patients)

• Infections: pneumonia, herpes virus infection (including cytomegalovirus - CMV), upper respiratory tract infection, severe blood or tissue infection (including rare cases with fatal outcomes)
• Heart and lungs: palpitations, irregular heartbeat, congestive heart failure, weak heart muscle, high blood pressure, high blood pressure in the lungs, cough
• Digestive problems: changes in appetite, changes in taste, abdominal distension or swelling, colon inflammation, constipation, gastroesophageal reflux, oral ulcers, weight loss, weight gain, gastritis
• Skin, hair, eyes, general: tingling sensation on the skin, itching, dry skin, acne, skin inflammation, persistent ringing in the ears, hair loss, excessive sweating, visual disturbances (including blurred vision and distorted vision), dry eyes, bruising, depression, insomnia, hot flashes, dizziness, bruising, anorexia, somnolence, generalized edema
• Pain: joint pain, muscle weakness, chest pain, pain in the hands and feet, chills, muscle and joint stiffness, muscle spasms
• Laboratory tests: fluid around the heart, fluid in the lungs, heart arrhythmias, febrile neutropenia, gastrointestinal bleeding, high uric acid levels in the blood

Uncommon adverse effects (may affect up to 1 in 100 patients)

• Heart and lungs: heart attack (including fatal outcome), inflammation of the membrane surrounding the heart (pericarditis), irregular heartbeat, chest pain due to reduced blood flow to the heart (angina), low blood pressure, narrowing of the airways that could cause breathing difficulties, asthma, high blood pressure in the arteries (blood vessels) that go to the lungs
• Digestive problems: pancreas inflammation, peptic ulcer, digestive tract inflammation, abdominal swelling, anal canal skin tear, difficulty swallowing, gallbladder inflammation, bile duct obstruction, gastroesophageal reflux (stomach acid and other contents return to the throat)
• Skin, hair, eyes, general: allergic reactions including sensitivity, red lumps on the skin (erythema nodosum), anxiety, confusion, mood swings, low sex drive, fainting, tremors, eye inflammation that can cause redness or pain, skin disease characterized by sensitivity, redness, well-defined spots with sudden onset of fever and elevated white blood cell count (neutrophilic dermatosis), hearing loss, sensitivity to light, visual disturbances, increased eye tearing, skin color changes, inflammation of the fatty tissue under the skin, skin ulcers, skin blisters, nail changes, hair changes, changes in hands and feet, kidney failure, frequent urination, breast enlargement in men, menstrual changes, general weakness and discomfort, low thyroid function, loss of balance while walking, osteonecrosis (a disease where blood flow to the bones is reduced, which can cause bone loss and death), arthritis, skin swelling anywhere on the body
• Pain: vein inflammation that can cause redness, sensitivity, and swelling, tendon inflammation
• Brain: memory loss
• Additional tests: abnormal blood test results and possibly kidney failure caused by tumor waste products during healing (tumor lysis syndrome), low albumin levels in blood, low lymphocyte levels (a type of white blood cell) in blood, high cholesterol levels in blood, lymph node swelling, cerebral hemorrhage, irregular heart activity, enlarged heart, liver inflammation, protein in urine, elevated creatine phosphokinase (an enzyme found mainly in the heart, brain, and skeletal muscles), elevated troponin (an enzyme found mainly in the heart and skeletal muscle), elevated gamma-glutamyl transferase (an enzyme found mainly in the liver), milky fluid around the lungs (chylothorax)

Rare adverse effects (may affect up to 1 in 1000 patients)

• Heart and lungs: right ventricular dilation, heart muscle inflammation, set of symptoms produced by blockage of blood flow to the heart muscle (acute coronary syndrome), heart attack (interruption of blood flow to the heart), coronary artery disease (of the heart), inflammation of the tissue that covers the heart and lungs, blood clots, blood clots in the lungs
• Digestive problems: loss of vital nutrients such as proteins from the digestive system, intestinal obstruction, anal fistula (abnormal opening of the anus to the surrounding skin), kidney failure, diabetes
• Skin, hair, eyes, general: convulsions, inflammation of the optic nerve that can cause complete or partial vision loss, bluish-purple spots on the skin, abnormally high thyroid function, thyroid gland inflammation, ataxia (associated with loss of muscle coordination), difficulty walking, spontaneous abortion, skin vessel inflammation, skin fibrosis
• Brain: stroke, temporary episode of neurological deficiency caused by loss of blood flow, facial nerve paralysis, dementia
• Immune system: severe allergic reactions
• Connective and musculoskeletal tissue: delayed fusion of the rounded ends that form joints (epiphyses); slow or delayed growth

Other adverse effects that have been reported with unknown frequency (cannot be estimated from available data)

• • Lung inflammation
  • Bleeding in the stomach or intestine that can cause death
  • Recurrence (reactivation) of hepatitis B virus infection if you have had hepatitis B in the past (a liver infection)
  • Reaction with fever, skin blisters, and mucous membrane ulcers
  • Kidney disorders with symptoms such as edema and abnormal laboratory test results such as protein in the urine and low protein levels in blood
• Damaged blood vessels known as thrombotic microangiopathy (TMA), which includes decreased red blood cell count, decreased platelet count, and blood clot formation.

Your doctor will check if you have any of these effects during your treatment.

Reporting adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of SPRYCEL

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the label of the bottle after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package contents and additional information

Composition of SPRYCEL

• The active ingredient is dasatinib. Each film-coated tablet contains 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, or 140 mg of dasatinib (as monohydrate).
• The other ingredients are:
• Core of the tablet:lactose monohydrate (see section 2 SPRYCEL contains lactose"); microcrystalline cellulose; sodium croscarmellose; hydroxypropylcellulose; magnesium stearate
• Coating:hypromellose; titanium dioxide (E171); macrogol 400

Appearance of the product and package contents

SPRYCEL 20 mg: the film-coated tablets are white to off-white, biconvex, round, with "BMS" engraved on one side and "527" on the other.

SPRYCEL 50 mg: the film-coated tablets are white to off-white, biconvex, oval, with "BMS" engraved on one side and "528" on the other.

SPRYCEL 70 mg: the film-coated tablets are white to off-white, biconvex, round, with "BMS" engraved on one side and "524" on the other.

SPRYCEL 80 mg: the film-coated tablets are white to off-white, biconvex, triangular, with "BMS 80" engraved on one side and "855" on the other.

SPRYCEL 100 mg: the film-coated tablets are white to off-white, biconvex, oval, with "BMS 100" engraved on one side and "852" on the other.

SPRYCEL 140 mg: the film-coated tablets are white to off-white, biconvex, round, with "BMS 140" engraved on one side and "857" on the other.

SPRYCEL 20 mg, 50 mg, or 70 mg film-coated tablets are available in packages containing 56 film-coated tablets in 4 calendar blister packs of 14 film-coated tablets each, and in packages with 60 x 1 film-coated tablets in precut unit-dose blisters. They are also available in child-resistant closure bottles with 60 film-coated tablets. Each box contains one bottle.

SPRYCEL 80 mg, 100 mg, or 140 mg film-coated tablets are available in packages containing 30 x 1 film-coated tablets in precut unit-dose blisters. They are also available in child-resistant closure bottles with 30 film-coated tablets. Each box contains one bottle.

Not all pack sizes may be marketed.

Marketing authorization holder

Bristol-Myers Squibb Pharma EEIG Plaza 254 Blanchardstown Corporate Park 2

Dublin 15, D15 T867 Ireland

Manufacturer

Swords Laboratories Unlimited Company T/A Bristol-Myers Squibb Pharmaceutical Operations, External Manufacturing

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

CATALENT ANAGNI S.R.L.

Loc. Fontana del Ceraso snc

Strada Provinciale 12 Casilina, 41

03012 Anagni (FR) Italy

Date of the last revision of this prospectus:

Detailed information about this medicine is available on the European Medicines Agency website:

http://www.emea.europa.eu. There are also links to other websites about rare diseases and orphan medicines.