Sprycel

Package leaflet: Information for the user

SPRYCEL 20 mg film-coated tablets, 50 mg film-coated tablets, 70 mg film-coated tablets, 80 mg film-coated tablets, 100 mg film-coated tablets, 140 mg film-coated tablets

dasatinib
Please 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 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 yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What SPRYCEL is and what it is used for
2. What you need to know before taking 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 leukemia (CML) in adults, adolescents, and children at least 1 year
of age. Leukemia is a cancer of the white blood cells. White blood cells normally help the body
fight infections. In people with CML, white blood cells called granulocytes
start to grow uncontrollably. SPRYCEL inhibits the growth of these leukemic cells.
SPRYCEL is also used to treat Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in adults, adolescents, and children at least 1 year of age, and for the treatment of lymphoid blast phase CML in adults who have not benefited from prior therapies. In individuals with ALL, white blood cells called lymphocytes multiply very rapidly and live much longer than normal. SPRYCEL inhibits the growth of these leukemic cells.
If you have any questions about how SPRYCEL works or why it has been prescribed for you,
please consult your doctor.

2. What you need to know before taking SPRYCEL

Do not take SPRYCEL

• if you are allergic to dasatinib or to 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
Talk to your doctor or pharmacist before taking SPRYCEL

• if you are taking medicines that thin the blood or prevent clots (see "Other medicines and SPRYCEL")
• if you have or have had liver or heart problems
• if you start experiencing breathing difficulties, chest pain, or cough while taking SPRYCEL: this could be a sign of fluid retention in the lungs or chest (which may be more common in patients aged 65 years or older) or could be due to changes in the blood vessels supplying the lungs
• if you have ever had or may currently have hepatitis B infection. This is because SPRYCEL could cause reactivation of hepatitis B, which in some cases can be fatal. Your doctor will carefully monitor you for signs of this infection before starting treatment.
• if you develop bruising, bleeding, fever, fatigue, or confusion while taking SPRYCEL, contact your doctor. These may be signs of damage to blood vessels known as thrombotic microangiopathy (TMA).

Your doctor will need to monitor your clinical condition regularly to ensure that SPRYCEL is
having the desired effect. Additionally, you will have regular blood tests while taking
SPRYCEL.
Children and adolescents
Do not give this medicine to children under one year of age. Experience with SPRYCEL
in this age group is limited. The growth and bone development of children taking
SPRYCEL will be closely monitored.
Other medicines and SPRYCEL
Tell your doctor if you are taking, have recently taken, or might take any other
medicines.
SPRYCEL is mainly metabolized by the liver. Some medicines may interfere with
the effect of SPRYCEL when taken at the same time as SPRYCEL.
These medicines must not be used with SPRYCEL:

• ketoconazole, itraconazole – which are antifungal medicines
• erythromycin, clarithromycin, telithromycin – which are antibiotics
• ritonavir – which is an antiviral medicine
• phenytoin, carbamazepine, phenobarbital – which are treatments for epilepsy
• rifampicin – which is a treatment for tuberculosis
• famotidine, omeprazole – which are medicines that block acid production in the stomach
• St John’s wort – a herbal preparation obtained without prescription used for the treatment of depression and other conditions (also known as Hypericum perforatum )

Do not take medicines that neutralize stomach acid ( antacids such as aluminium hydroxide
or magnesium hydroxide) within 2 hours before or 2 hours after taking SPRYCEL.
Tell your doctor if you are taking medicines that thin the blood or prevent clots.
SPRYCEL with food and drink
Do not take SPRYCEL with grapefruit or grapefruit juice.
Pregnancy and breastfeeding
If you are pregnant or suspect you may be pregnant, inform your doctor immediately.
SPRYCEL must not be used during pregnancy unless strictly necessary. Your
doctor will discuss with you the potential risks of taking SPRYCEL during pregnancy.
Both men and women taking SPRYCEL will be advised to use an effective contraceptive method during treatment.
If you are breastfeeding, inform your doctor. Breastfeeding must be discontinued during treatment with SPRYCEL.
Driving and using machines
If you experience side effects such as dizziness or blurred vision, take special
care when driving or operating machinery.
SPRYCEL contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him or her before taking this medicine.

3. How to take SPRYCEL

SPRYCEL will only be prescribed by a doctor experienced in the treatment of leukemia. Always take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist. SPRYCEL is prescribed for adults and children aged at least 1 year.

The recommended initial dose in adult patients with chronic-phase chronic myeloid leukemia (CML) is 100 mg once daily.
The recommended initial dose in adult patients with accelerated-phase or blast-phase CML, or with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), is 140 mg once daily.
The dosage for children with chronic-phase CML or Ph+ ALL is based on body weight.

SPRYCEL is administered orally once daily as either SPRYCEL tablets or SPRYCEL oral suspension powder. SPRYCEL tablets are not recommended for patients weighing less than 10 kg. For patients weighing less than 10 kg or for patients unable to swallow tablets, the oral suspension powder should be used. When switching between formulations (i.e., between tablets and oral suspension powder), the dose may change; therefore, do not switch from one formulation to the other without medical advice.

Your doctor will determine the appropriate formulation and dose based on body weight, any side effects, and response to treatment. The initial dose of SPRYCEL for children is calculated according to body weight, as shown below:

Body weight (kg) Daily dose (mg)
from 10 to <20 kg 40 mg
from 20 to <30 kg 60 mg
from 30 to <45 kg 70 mg
≥45 kg 100 mg

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

Depending on your response to treatment, your doctor may recommend a higher or lower dose, or even a brief interruption of treatment. For higher or lower doses, you may need to take combinations of tablets with different strengths.

Tablets may be supplied in calendar blister packs. These are blister packs labeled with the days of the week. Arrows indicate the next tablet to take according to your treatment schedule.

How to take SPRYCEL
Take the tablets at the same time each day. Swallow the tablets whole without crushing, splitting, or chewing them. Do not take dissolved tablets. If you crush, split, chew, or disperse the tablets, you cannot be sure of receiving the correct dose. SPRYCEL tablets may be taken with or without food.

Special handling precautions for SPRYCEL
It is unlikely that SPRYCEL tablets will break. However, if a tablet does break, individuals other than the patient must wear gloves when handling SPRYCEL.

How long to take SPRYCEL
Take SPRYCEL daily until your doctor tells you to stop. Make sure you continue taking SPRYCEL for the entire duration prescribed.

If you take more SPRYCEL than you should
If you accidentally take too many tablets, contact your doctor immediately. You may require medical attention.

If you forget to take SPRYCEL
Do not take a double dose to make up for the missed tablet. Take the next scheduled dose at the usual time.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following may all be symptoms of serious side effects:

• if you have chest pain, difficulty breathing, cough and fainting
• if you experience unexpected bleeding or bruising without injury
• if you find blood in your vomit, stools or urine, or your stools are black
• if you develop signs of infection such as fever, severe chills
• if you have fever, mouth or throat pain, blisters or peeling of the skin and/or mucous membranes
  Contact your doctor immediately if you notice any of the above effects.

Very common side effects (may affect more than 1 in 10 people)

• Infections (includes bacterial, viral and fungal infections)
• Heart and lungs: shortness of breath
• Digestive system problems: diarrhoea, feeling or state of being unwell (nausea, vomiting)
• Skin, hair, eyes, general: rash, fever, swelling of the face, hands and feet, headache, feeling of tiredness or weakness, bleeding
• Pain: muscle pain (during or after treatment interruption), abdominal pain
• Laboratory and instrumental tests may show: low platelet count, low white blood cell count (neutropenia), anaemia, presence of fluid in the lungs (effusion)

Common side effects (may affect up to 1 in 10 people)

• Infections: pneumonia, herpes virus infection (including cytomegalovirus - CMV), upper respiratory tract infections, severe blood and tissue infections (including uncommon cases with fatal outcomes)
• Heart and lungs: palpitations, irregular heartbeat, congestive heart failure, myocardial weakness, high blood pressure, increased pressure in the lungs, cough
• Digestive system problems: loss of appetite, taste disturbances, swelling or distension of the abdomen, inflammation of the colon, constipation, heartburn, mouth ulceration, weight gain, weight loss, gastritis
• Skin, hair, eyes, general: tingling of the skin, itching, dry skin, acne, skin inflammation, persistent ringing in the ears (tinnitus), hair loss, excessive sweating, eye disorders (including blurred vision and visual disturbances), dry eyes, bruising, depression, insomnia, hot flushes, dizziness, contusion (bruise), anorexia, somnolence, generalized oedema
• Pain: joint pain, muscle weakness, chest pain, pain in hands and feet, chills, muscle and joint stiffness, muscle spasm
• Laboratory and instrumental tests may show: fluid around the heart, fluid in the lungs, arrhythmia, febrile neutropenia, gastrointestinal bleeding, elevated levels of uric acid in the blood

Uncommon side effects (may affect up to 1 in 100 people)

• Heart and lungs: heart attack (including fatal cases), inflammation of the lining (fibrous sac) surrounding the heart, irregular heartbeat, chest pain due to lack of blood flow to the heart (angina), low blood pressure, narrowing of the airways which may cause breathing difficulties, asthma, increased blood pressure in the arteries (blood vessels) of the lungs
• Digestive system problems: inflammation of the pancreas, peptic ulcer, oesophagitis, bloated abdomen, tear in the skin of the anal canal, difficulty swallowing, inflammation of the gallbladder, obstruction of bile ducts, gastro-oesophageal reflux (a condition where stomach acids and other contents rise up into the throat)
• Skin, hair, eyes, general: allergic reactions including sensitivity, red nodules on the skin (erythema nodosum), anxiety, confusion, mood swings, decreased sexual desire, fainting, tremors, eye inflammation causing redness or pain, a skin disease characterised by sensitivity, redness, well-defined patches with sudden onset of fever and elevated white blood cell count (neutrophilic dermatosis), hearing loss, light sensitivity, impaired vision, increased eye tearing, skin pigmentation disorders, inflammation of the fat tissue under the skin, skin ulcers, blisters on the skin, nail disorders, hair and hair disorders, hand-foot syndrome, renal failure, urinary frequency, breast enlargement in men, menstrual disorder, general weakness and malaise, decreased thyroid function, loss of balance while walking, osteonecrosis (a disease caused by reduced blood flow to the bones, which may lead to bone loss and bone death), arthritis, skin swelling anywhere on the body
• Pain: inflammation of veins which may cause redness, tenderness and swelling, tendon inflammation
• Brain: memory loss
• Laboratory and instrumental tests may show: abnormal blood test results and possible impairment of kidney function due to products from the breakdown of destroyed tumour cells (tumour lysis syndrome), low levels of albumin in the blood, low levels of lymphocytes (a type of white blood cells) in the blood, high levels of cholesterol in the blood, swollen lymph nodes, cerebral haemorrhage, irregularities in the heart's electrical activity, heart enlargement, liver inflammation, protein in urine, increased creatine phosphokinase (an enzyme found mainly in the heart, brain and skeletal muscles), increased troponin (an enzyme found mainly in the heart and skeletal muscles), increased gamma-glutamyltransferase (an enzyme found mainly in the liver), milky fluid around the lungs (chylothorax)

Rare side effects (may affect up to 1 in 1,000 people)

• Heart and lungs: enlargement of the right ventricle of the heart, inflammation of the heart muscle, a set of conditions resulting from blocked blood flow to the heart muscle (acute coronary syndrome), cardiac arrest (cessation of blood flow from the heart), coronary heart disease, inflammation of the tissue lining the heart and lungs, blood clots, blood clots in the lungs
• Digestive system problems: loss of vital nutrients from the digestive tract, such as proteins, intestinal obstruction, anal fistula (an abnormal crack from the anus to the surrounding skin), reduced kidney function, diabetes
• Skin, hair, eyes, general: seizures, inflammation of the optic nerve which may cause partial or complete vision loss, blue-purple patches on the skin, abnormally increased thyroid function, inflammation of the thyroid gland, ataxia (a condition associated with lack of muscle coordination), difficulty walking, miscarriage, inflammation of blood vessels in the skin, skin fibrosis
• Brain: stroke, transient episode of neurological dysfunction caused by loss of blood flow, facial nerve paralysis, dementia
• Immune system: severe allergic reaction
• Musculoskeletal and connective tissue: delayed fusion of the rounded ends forming the joints (epiphyses); slowed or delayed growth

Other side effects reported with unknown frequency (cannot be estimated from the available data):

• pneumonia
• bleeding in the stomach or intestines which may cause death
• reactivation of hepatitis B infection if you have had hepatitis B in the past (a liver infection)
• a reaction with fever, blisters on the skin and mucosal ulceration
• kidney disease with symptoms including oedema and abnormal laboratory test results such as protein in the urine and low levels of protein in the blood
• damage to blood vessels known as thrombotic microangiopathy (TMA), including decreased red blood cell count, decreased platelet count and formation of blood clots

Your doctor will monitor some of these side effects during treatment.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store SPRYCEL

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label, blister pack, or carton after "Exp". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What SPRYCEL contains

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

Description of the appearance of SPRYCEL and package contents

SPRYCEL 20 mg: the film-coated tablet is white to almost white, biconvex, round, with "BMS" engraved on one side and "527" on the other side.
SPRYCEL 50 mg: the film-coated tablet is white to almost white, biconvex, oval, with "BMS" engraved on one side and "528" on the other side.
SPRYCEL 70 mg: the film-coated tablet is white to almost white, biconvex, round, with "BMS" engraved on one side and "524" on the other side.
SPRYCEL 80 mg: the film-coated tablet is white to almost white, biconvex, triangular, with "BMS 80" engraved on one side and "855" on the other side.
SPRYCEL 100 mg: the film-coated tablet is white to almost white, biconvex, oval, with "BMS 100" engraved on one side and "852" on the other side.
SPRYCEL 140 mg: the film-coated tablet is white to almost white, biconvex, round, with "BMS 140" engraved on one side and "857" on the other side.

SPRYCEL 20 mg, 50 mg or 70 mg film-coated tablets are available in cartons containing 56 film-coated tablets in 4 calendar blister packs of 14 film-coated tablets each, or in cartons containing 60 x 1 film-coated tablets in unit dose divisible blisters. They are also available in child-resistant bottles containing 60 film-coated tablets. Each carton contains one bottle.
SPRYCEL 80 mg, 100 mg or 140 mg film-coated tablets are available in cartons containing 30 x 1 film-coated tablets in unit dose divisible blisters. They are also available in child-resistant bottles containing 30 film-coated tablets. Each carton 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

More detailed information on this medicinal product is available on the European Medicines Agency website:
http://www.emea.europa.eu. In addition, links to other websites on rare diseases and related therapeutic treatments are provided.

Package leaflet: information for the user

SPRYCEL 10 mg/mL powder for oral suspension

dasatinib
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What SPRYCEL is and what it is used for
2. What you need to know before taking 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 leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL)
in adolescents and children aged one year and older. Leukemia is a cancer of the white blood cells.
White blood cells normally help the body fight infections. In people with CML, white blood cells called granulocytes
start to grow uncontrollably. SPRYCEL inhibits the growth of these cells.
If you have any questions about how SPRYCEL works or why it has been prescribed for you or your child,
please consult your doctor.

2. What you need to know before taking SPRYCEL

Do not take SPRYCEL

• if you are allergic to dasatinib or to any of the other ingredients of this medicine (listed in section 6). If you think you or your child may be allergic, consult your doctor.

Warnings and precautions
Talk to your doctor or pharmacist before taking SPRYCEL

• if you are taking medicines that thin the blood or prevent clotting (see "Other medicines and SPRYCEL")

• if you have or have had liver or heart problems

• if you start experiencing breathing difficulties, chest pain, or cough while taking SPRYCEL: this could be a sign of fluid retention in the lungs or chest (which may be more common in patients aged 65 years or older), or it could be due to changes in the blood vessels supplying the lungs

• if you have had or may currently have hepatitis B infection. This is because SPRYCEL could cause reactivation of hepatitis B, which in some cases can be fatal.
  Patients will be closely monitored by their doctor for signs of this infection before starting treatment.

• if you develop bruising, bleeding, fever, fatigue, or confusion while taking SPRYCEL, contact your doctor. These may be signs of damage to blood vessels known as thrombotic microangiopathy (TMA).

Your doctor will need to monitor your clinical condition regularly to ensure SPRYCEL is having the desired effect. In addition, you or your child will undergo regular blood tests while taking SPRYCEL.
Children and adolescents
Do not give this medicine to children under one year of age.
The growth and bone development of children taking SPRYCEL will be closely monitored.
Other medicines and SPRYCEL
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
SPRYCEL is mainly metabolized by the liver. Some medicines may interfere with the effect of SPRYCEL when taken at the same time as SPRYCEL.
These medicines must not be used with SPRYCEL:

• ketoconazole, itraconazole – which are antifungal medicines
• erythromycin, clarithromycin, telithromycin – which are antibiotics
• ritonavir – which is an antiviral medicine
• phenytoin, carbamazepine, phenobarbital – which are treatments for epilepsy
• rifampicin – which is a treatment for tuberculosis
• famotidine, omeprazole – which are medicines that block acid production in the stomach
• St. John’s wort – a herbal preparation obtained without prescription used for the treatment of depression and other conditions (also known as Hypericum perforatum)

Do not take medicines that neutralize stomach acid (antacids such as aluminium hydroxide or magnesium hydroxide) within 2 hours before or 2 hours after taking SPRYCEL.
Tell your doctor if you are taking medicines that thin the blood or prevent clotting.
SPRYCEL with food and drink
Do not take SPRYCEL with grapefruit or grapefruit juice.
Pregnancy and breastfeeding
If you are pregnant or suspect you may be pregnant, inform your doctor immediately.
SPRYCEL must not be used during pregnancy unless strictly necessary. Your doctor will discuss with you the potential risks of taking SPRYCEL during pregnancy.
Both men and women taking SPRYCEL will be advised to use an effective method of contraception during treatment.
If you are breastfeeding, inform your doctor. Breastfeeding must be discontinued during treatment with SPRYCEL.
Driving and using machines
If you experience side effects such as dizziness or blurred vision, take particular care when driving or operating machinery.
SPRYCEL contains sucrose
If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
It contains 0.29 g of sucrose per mL of oral suspension. This should be considered in patients with diabetes mellitus. It may be harmful to teeth.
SPRYCEL contains sodium
This medicine contains 2.1 mg of sodium (the main component of table salt) per mL of SPRYCEL oral suspension. At the maximum daily dose of 16 mL of oral suspension, this corresponds to 1.7% of the maximum daily intake recommended by the WHO in the diet, which is 2 g of sodium for an adult.
SPRYCEL contains benzoic acid and sodium benzoate
SPRYCEL contains 0.25 mg of benzoic acid per mL of oral suspension and 0.25 mg of sodium benzoate per mL of oral suspension.
Benzoic acid/sodium benzoate may increase jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks of age).
SPRYCEL contains benzyl alcohol
SPRYCEL contains 0.017 mg of benzyl alcohol per mL of oral suspension.
Benzyl alcohol may cause allergic reactions.
The use of SPRYCEL is not recommended during pregnancy. Ask your doctor or pharmacist for advice if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol may accumulate in the body and cause unwanted effects (such as metabolic acidosis).
Ask your doctor or pharmacist for advice if you have liver or kidney disease. This is because large amounts of benzyl alcohol may accumulate in the body and cause unwanted effects (such as metabolic acidosis).
SPRYCEL contains sulfur dioxide (E220)
Rarely, it may cause severe hypersensitivity reactions and bronchospasm.

3. How to take SPRYCEL

SPRYCEL will only be prescribed by a physician experienced in the treatment of leukemia. Always take this medicine exactly as your doctor has instructed you. If you have any doubts, consult your doctor or pharmacist.
Take SPRYCEL oral suspension once daily. Your doctor will determine the appropriate dose based on body weight. The initial dose of SPRYCEL is calculated according to body weight as shown below:
Body weight (kg) Daily dose, mL (mg)
from 5 to <10 kg 4 mL (40 mg)
from 10 to <20 kg 6 mL (60 mg)
from 20 to <30 kg 9 mL (90 mg)
from 30 to <45 kg 10.5 mL (105 mg)
at least 45 kg 12 mL (120 mg)
SPRYCEL is also available in tablet form for adults and children aged one year and older weighing more than 10 kg. For patients weighing less than 10 kg and for patients unable to swallow tablets, the oral suspension powder must be used. When switching between formulations (i.e., between tablets and oral suspension powder), the dose may change; therefore, do not switch from one formulation to the other on your own. Your doctor will decide the appropriate formulation and dose based on body weight, possible side effects, and response to treatment.
There is no recommended dose of SPRYCEL for children under 1 year of age.
Depending on your response to treatment, your doctor may recommend a higher or lower dose, or even a brief interruption of treatment.
How to take SPRYCEL
Your pharmacist or a qualified healthcare professional will reconstitute (mix to form a liquid) the SPRYCEL powder for oral suspension to prepare SPRYCEL oral suspension before dispensing it.
SPRYCEL must be taken at the same time every day. SPRYCEL may be taken with or without food. SPRYCEL oral suspension may be mixed with milk, yogurt, juice, or applesauce.
See the "Instructions for Use" at the end of this leaflet for guidance on administering the dose of SPRYCEL oral suspension.
Special handling precautions for SPRYCEL
Individuals other than the patient should wear gloves when handling SPRYCEL.
Pregnant women or those breastfeeding should avoid exposure to SPRYCEL powder for oral suspension.
How long to take SPRYCEL
Take SPRYCEL daily until your doctor tells you to stop. Make sure to take SPRYCEL for the entire duration prescribed.
If you take more SPRYCEL than you should
If you accidentally take too much SPRYCEL, contact your doctor immediately. You may require medical attention.
If you forget to take SPRYCEL
Do not take a double dose to make up for a missed dose. Take the next scheduled dose at the usual time.
If you have any questions about 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.
The following may all be symptoms of serious side effects:

• if you have chest pain, difficulty breathing, coughing and fainting
• if you experience unexpected bleeding or bruising without injury
• if you find blood in your vomit, stools or urine, or your stools are black
• if you develop signs of infection such as fever, severe chills
• if you have fever, mouth or throat pain, blisters or peeling of the skin and/or mucous membranes
  Contact your doctor immediately if you notice any of the above effects.

Very common side effects (may affect more than 1 in 10 people)

• Infections (includes bacterial, viral and fungal infections)
• Heart and lungs: shortness of breath
• Digestive problems: diarrhoea, feeling unwell (nausea, vomiting)
• Skin, hair, eyes, general: rash, fever, swelling of the face, hands and feet, headache, feeling tired or weak, bleeding
• Pain: muscle pain (during or after stopping treatment), abdominal pain
• Laboratory and instrumental tests may show: low platelet count, low white blood cell count (neutropenia), anaemia, fluid in the lungs (effusion)

Common side effects (may affect up to 1 in 10 people)

• Infections: pneumonia, herpes virus infection (including cytomegalovirus - CMV), upper respiratory tract infections, severe blood and tissue infections (including uncommon cases with fatal outcomes)
• Heart and lungs: palpitations, irregular heartbeat, congestive heart failure, myocardial weakness, high blood pressure, increased pressure in the lungs, cough
• Digestive problems: loss of appetite, taste disturbances, bloating or swelling of the abdomen, inflammation of the colon, constipation, heartburn, mouth ulceration, weight gain, weight loss, gastritis
• Skin, hair, eyes, general: skin tingling, itching, dry skin, acne, skin inflammation, persistent ringing in the ears, hair loss, excessive sweating, eye disorders (including blurred vision and visual disturbances), dry eyes, bruising, depression, insomnia, hot flushes, dizziness, contusion (bruise), anorexia, drowsiness, generalized oedema
• Pain: joint pain, muscle weakness, chest pain, pain in hands and feet, chills, muscle and joint stiffness, muscle spasm
• Laboratory and instrumental tests may show: fluid around the heart, fluid in the lungs, arrhythmia, febrile neutropenia, gastrointestinal bleeding, elevated levels of uric acid in the blood

Uncommon side effects (may affect up to 1 in 100 people)

• Heart and lungs: heart attack (including fatal cases), inflammation of the sac (fibrous sac) surrounding the heart, irregular heartbeat, chest pain due to reduced blood flow to the heart (angina), low blood pressure, narrowing of the airways which may cause breathing difficulties, asthma, increased blood pressure in the pulmonary arteries (blood vessels) of the lungs
• Digestive problems: inflammation of the pancreas, peptic ulcer, oesophagitis, bloated abdomen, anal fissure, difficulty swallowing, inflammation of the gallbladder, bile duct obstruction, gastro-oesophageal reflux (a condition where stomach acids and other contents flow back into the throat)
• Skin, hair, eyes, general: allergic reactions including sensitivity, red nodules on the skin (erythema nodosum), anxiety, confusion, mood swings, decreased sexual desire, fainting, tremors, eye inflammation causing redness or pain, a skin disease characterized by sensitivity, redness, well-defined patches with sudden onset of fever and elevated white blood cell count (neutrophilic dermatosis), hearing loss, light sensitivity, impaired vision, increased eye tearing, skin pigmentation disorders, inflammation of subcutaneous fat tissue, skin ulcers, skin blisters, nail disorders, hair and hair disorders, hand-foot syndrome, kidney failure, urinary frequency, breast enlargement in men, menstrual disorders, general weakness and malaise, reduced thyroid function, loss of balance while walking, osteonecrosis (a disease due to reduced blood supply to bones, which may cause bone loss and bone death), arthritis, skin swelling anywhere on the body
• Pain: vein inflammation which may cause redness, tenderness and swelling, tendon inflammation
• Brain: memory loss
• Laboratory and instrumental tests may show: abnormal blood test results and possible kidney function impairment due to tumour lysis products (tumour lysis syndrome), low albumin levels in the blood, low lymphocyte levels (a type of white blood cell) in the blood, high cholesterol levels in the blood, swollen lymph nodes,
  cerebral haemorrhage, irregularities in the heart's electrical activity, heart enlargement,
  liver inflammation, protein in urine, increased creatine phosphokinase (an enzyme
  mainly found in the heart, brain and skeletal muscles), elevated troponin
  (an enzyme mainly found in the heart and skeletal muscles),
  elevated gamma-glutamyltransferase (an enzyme mainly found in the liver),
  milky fluid around the lungs (chylothorax)

Rare side effects (may affect up to 1 in 1,000 people)

• Heart and lungs: right ventricular enlargement of the heart, inflammation of the heart muscle, a set of conditions resulting from blocked blood flow to the heart muscle (acute coronary syndrome), cardiac arrest (cessation of blood flow from the heart), coronary artery disease (of the heart), inflammation of the tissue lining the heart and lungs, blood clots, blood clots in the lungs
• Digestive problems: loss from the gastrointestinal tract of vital nutrients such as proteins, intestinal obstruction, anal fistula (an abnormal crack from the anus to the surrounding skin), reduced kidney function, diabetes
• Skin, hair, eyes, general: seizures, optic nerve inflammation which may cause partial or complete vision loss, blue-purple patches on the skin, abnormally increased thyroid function, thyroid gland inflammation, ataxia (a condition associated with lack of muscle coordination), difficulty walking, miscarriage, inflammation of blood vessels in the skin, skin fibrosis
• Brain: stroke, transient episode of neurological dysfunction caused by loss of blood flow, facial nerve paralysis, dementia
• Immune system: severe allergic reaction
• Musculoskeletal and connective tissue: delayed fusion of the rounded ends forming the joints (epiphyses); slowed or delayed growth

Other side effects reported with unknown frequency (cannot be estimated from the available data):

• pneumonia
• bleeding in the stomach or intestines which may cause death
• reactivation of hepatitis B infection if you have had hepatitis B in the past (a liver infection)
• a reaction with fever, skin blisters and mucosal ulceration
• kidney disease with symptoms including oedema and abnormal laboratory test results such as protein in urine and low protein levels in blood
• Damage to blood vessels known as thrombotic microangiopathy (TMA), including decreased red blood cell count, decreased platelets and blood clot formation

Your doctor will monitor some of these side effects during treatment.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store SPRYCEL

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 vial label and the box after Exp. The expiry date refers to the last day of that month.

Powder
Store below 25°C.

After reconstitution
Store in a refrigerator (2°C–8°C). Do not freeze. Discard any unused suspension 60 days after reconstitution.

The reconstituted oral suspension mixed with milk, yogurt, juice, or apple puree may be stored at a temperature equal to or below 25°C for up to 1 hour.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What SPRYCEL contains

• The active substance is dasatinib. One vial of powder for oral suspension contains 990 mg of dasatinib (as monohydrate). After reconstitution, one vial contains 99 mL of oral suspension. Each mL of oral suspension contains 10 mg of dasatinib (as monohydrate).
• The other components are: sucrose, sodium carmellose, simethicone emulsion (containing simethicone, polyethylene glycol stearate sorbitan, polyoxyl stearate, glycerides, methylcellulose, xanthan gum, benzoic acid, sorbic acid, sulfuric acid), tartaric acid, trisodium citrate anhydrous, sodium benzoate (E211), hydrophobic colloidal silica, mixed berry flavour (containing: benzyl alcohol, sulfur dioxide) (see section 2 "What you need to know before taking SPRYCEL").

Description of the appearance of SPRYCEL and contents of the pack
SPRYCEL is a powder for oral suspension, white to off-white in colour, which forms an opaque suspension white to yellow in colour after reconstitution with water.
A 120 mL plastic bottle (with child-resistant closure) contains 33 g of powder for oral suspension.
After reconstitution, the bottle contains 99 mL of oral suspension, of which 90 mL are intended for dosing and administration.
Each pack also contains a press-in bottle adapter (PIBA) and a 12 mL oral dosing syringe in a sealed plastic pouch.
Each carton contains one bottle.
Marketing Authorisation Holder
Bristol-Myers Squibb Pharma EEIG
Plaza 254
Blanchardstown Corporate Park 2
Dublin 15, D15 T867
Ireland
Manufacturer
Swords Laboratories Unlimited Company T/A Lawrence Laboratories
Unit 12 & 15, Distribution Centre
Shannon Industrial Estate
Shannon, Co. Clare, V14 DD39
Ireland
More detailed information on this medicinal product is available on the website of the European Medicines Agency,
http://www.emea.europa.eu. In addition, links to other websites on rare diseases and related therapeutic treatments are provided.
Patient administration instructions
These instructions show how to administer a dose of SPRYCEL oral suspension to the patient.
After reconstitution performed by your pharmacist or healthcare professional, the oral suspension must be administered exclusively using the oral dosing syringe provided in the package. Your doctor will determine the appropriate dose based on age and body weight. Be sure to read and understand these instructions before using the oral suspension.
What you need to know before using this medicine

• Take SPRYCEL oral suspension either on an empty or full stomach.
• Wash your hands before and after each use.
• Store the reconstituted oral suspension in the refrigerator (2°C–8°C). Do not freeze.
• Review the total prescribed dose and determine the required millilitres (mL).
• If the required amount exceeds 11 mL, it must be divided into 2 doses, as described below:

How to divide a dose greater than 11 mL

Total prescribed dose (mL)	First dose (mL)	Second dose (mL)
12	6	6
13	7	6
14	7	7
15	8	7
16	8	8

Before preparing a dose of SPRYCEL oral suspension for administration to the
patient, prepare the following:

• Paper towel

• 1 bottle of SPRYCEL oral suspension containing an opaque white to yellow suspension.
• The 12 mL oral dosing syringe provided with the bottle.
• A small container filled with water to rinse the syringe.

Carefully prepare SPRYCEL oral suspension for administration, measure the dose, and fill the syringe as follows:

1. Mix SPRYCEL

oral suspension in the
closed bottle by shaking
for 30 seconds.

• Shake well before each use.

2. Remove the cap from the

bottle. Ensure that the
adapter attached to the
bottle for syringe placement
is firmly pressed into the
bottle.

3. Before starting, look at the

graduation marks on the side
of the syringe to determine
the amount to be filled. The
graduated marks on the
syringe indicate mL. Locate
the mark corresponding to
the dose prescribed by the
doctor. Before each use,
ensure that the syringe
plunger is fully pushed into
the bottom of the syringe
barrel.

4. Holding the bottle upright,

firmly insert the tip of the
syringe into the bottle
adapter.

5. While keeping the tip of the

syringe firmly in the bottle,
invert the bottle with the
syrine upside down.

6. Slowly draw up the prescribed

amount of SPRYCEL oral
suspension by pulling back
the syringe plunger until
the prescribed dose mark
is reached.

• Hold the plunger steady to prevent it from moving. A vacuum may form when pulling the plunger back into the syringe barrel.
• If the prescribed dose cannot be obtained from one bottle, use the second bottle to complete the prescribed dose. Make sure to shake the second bottle before use.

7. Keeping the tip of the

syringe firmly inserted in
the bottle, return the bottle
with the syringe to an
upright position.

8. Remove the syringe from

the bottle, taking care not
to press the plunger.

9. With the patient in an upright

position, insert the tip of
the syringe into the mouth,
between the cheek and the
tongue. Slowly push down
the plunger until the entire
dose has been administered.

• Ensure that the patient has swallowed the entire dose.
• If a second dose is required to achieve the total prescribed dose, repeat steps 3 to 10.
• Replace the cap on the bottle and close tightly. Store in an upright position.

10. After each

use, wash both the
external and internal
parts of the syringe and
allow it to air dry for
reuse the next day.

• Do not wash in a dishwasher.
• Do not disassemble the syringe to avoid damaging it. 11. For instructions on the disposal of unused medicines, syringes, and bottles, refer to the package leaflet (see section 5 ‘How to store SPRYCEL’).

For any questions regarding the preparation or administration of a dose of SPRYCEL
oral suspension, consult your doctor, pharmacist, or nurse.

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The following information is intended exclusively for physicians or healthcare professionals:
Instructions for reconstitution of the oral suspension powder
SPRYCEL powder for oral suspension must be reconstituted as follows:
Note: If reconstituting the contents of more than one bottle, complete one bottle at a time.
Wash hands before beginning reconstitution. This procedure must be performed on a clean surface.
Step 1: Tap the bottom of each bottle (containing 33 g of SPRYCEL powder for oral suspension) gently to loosen the powder. Remove the child-resistant cap and the sealed membrane. Add 77.0 mL of purified water all at once to the bottle, then close tightly with the cap.
Step 2: Immediately invert the bottle and shake vigorously for at least 60 seconds to obtain a uniform suspension. If lumps are still visible, continue shaking until they disappear. This reconstitution yields 90 mL (withdrawable volume) of SPRYCEL oral suspension at a concentration of 10 mg/mL.
Step 3: Remove the cap, insert the press-in bottle adapter (PIBA) into the neck of the bottle, and close the bottle securely with the child-resistant cap.
Step 4: Write the expiration date of the reconstituted oral suspension on the bottle label (the expiration date of the reconstituted oral suspension is 60 days from the date of reconstitution).
Step 5: Provide the patient or caregiver with the bottle containing the press-in bottle adapter (PIBA) inserted, the package leaflet, and the oral dosing syringe in the original carton. Remind the patient or caregiver to shake the bottle vigorously before each use.