Dasatinib EG

Patient Information Leaflet: Information for the User

Dasatinib EG 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

Generic medicine
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 other people, even if they have the same symptoms as yours, because it may be harmful to them.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Dasatinib EG is and what it is used for

Dasatinib EG contains the active substance dasatinib. Dasatinib EG is used to treat adult patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) who have not benefited from prior therapies. Leukemia is a cancer of the white blood cells. White blood cells normally help the body fight infections. In patients with ALL, a type of white blood cell called lymphocytes multiplies very rapidly and lives much longer than normal. Dasatinib EG inhibits the growth of these leukemic cells.
If you have any questions about how Dasatinib EG works or why it has been prescribed for you, please consult your doctor.

2. What you need to know before taking Dasatinib EG

Do not take Dasatinib EG

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Dasatinib EG:

• if you are taking medicines that thin the blood or prevent blood clots (see "Other medicines and Dasatinib EG");
• if you have or have had liver or heart problems;
• if you start experiencing breathing difficulties, chest pain or cough while taking dasatinib: this

could be a symptom of fluid retention in the lungs or chest (which may be more common
in patients over 65 years of age) or could be due to changes in the blood vessels supplying
the lungs;

• if you have had or may currently have a hepatitis B infection. This is because dasatinib can reactivate hepatitis B, which could be fatal in some cases. Your doctor will carefully monitor you before starting treatment to detect any signs of this infection.

Your doctor should regularly monitor your clinical condition to check whether dasatinib is having the desired effect. In addition, you will have regular blood tests while taking Dasatinib EG.
Children and adolescents
Dasatinib EG is not recommended for patients under 18 years of age. Experience with dasatinib in this age group is limited.
Other medicines and Dasatinib EG
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
Dasatinib is mainly metabolized by the liver. Some medicines may interfere with the effect of dasatinib when taken at the same time.
These medicines must not be used with dasatinib:

• ketoconazole, itraconazole – which are antifungal medicines;
• erythromycin, clarithromycin, telithromycin – which are antibiotics;
• ritonavir – which is an antiviral medicine;
• dexamethasone – which is a corticosteroid;
• 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 – an herbal preparation available 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 dasatinib. Tell your doctor if you are taking medicines that thin the blood or prevent clots.

Dasatinib EG with food and drink
Do not take dasatinib with grapefruit or grapefruit juice.
Pregnancy and breastfeeding
If you are pregnant or think you might be, inform your doctor immediately. Dasatinib
must not be used during pregnancy unless strictly necessary. Your doctor will discuss with you the potential risks of taking dasatinib during pregnancy.
Both men and women taking dasatinib will be advised to use an effective method of contraception during treatment.
Tell your doctor if you are breastfeeding. Breastfeeding must be discontinued during treatment with dasatinib.
Driving and using machines
If you experience side effects such as dizziness or blurred vision, exercise particular caution when driving or operating machinery. It is not known whether dasatinib affects the ability to drive or use machines.
Dasatinib EG contains:
Lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.
Sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dosage unit, i.e. essentially ‘sodium-free’.

3. How to take Dasatinib EG

Dasatinib EG will only be prescribed by a doctor experienced in the treatment of leukaemia.
Always take this medicine exactly as instructed by your doctor. If you have any doubts, consult your
doctor or pharmacist. Dasatinib EG is prescribed for adults.
The recommended starting dose for patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) is 140 mg once daily.
Take the tablets at the same time each day.
Depending on how you respond 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.
How to take Dasatinib EG
Swallow the tablets whole. Do not crush them. The tablets may be taken with or without food.
Special handling precautions for Dasatinib EG
It is unlikely that Dasatinib EG tablets will break. However, if this should happen, individuals other than the patient must wear gloves when handling Dasatinib EG.
How long to take Dasatinib EG
Continue taking Dasatinib EG until your doctor tells you to stop treatment. Make sure you take Dasatinib EG for the entire duration prescribed.
If you take more Dasatinib EG than you should
If you have accidentally taken too many tablets, contact your doctor immediately. You may require medical attention.
If you forget to take Dasatinib EG
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 will get them.
The following may all be symptoms of serious side effects:

• if you have chest pain, difficulty breathing, cough, or fainting;
• if you experience unexpected bleeding or bruising without injury;
• if you find blood in your vomit, stools, or urine, or if your stools are black;
• if you develop signs of infection such as fever or severe chills;
• if you experience 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: diarrhea, 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, abdominal pain.
• Tests may show: low platelet count, low white blood cell count (neutropenia), anemia, presence of fluid in the lungs (effusion).

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

• Infections: pneumonia, herpes viral infection (including cytomegalovirus - CMV), upper respiratory tract infections, severe blood and tissue infections (including uncommon cases with fatal outcome).
• 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, altered taste, swelling or distension of the abdomen, inflammation of the colon, constipation, heartburn, mouth ulcers, weight gain, weight loss, gastritis.
• Skin, hair, eyes, general: skin burning, 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, bruising (contusion), anorexia, drowsiness, generalized edema.
• Pain: joint pain, muscle weakness, chest pain, pain in hands and feet, chills, muscle and joint stiffness, muscle spasms.
• Tests may show: fluid around the heart, fluid in the lungs, arrhythmia, febrile neutropenia, gastrointestinal bleeding, elevated blood uric acid levels.

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

• Heart and lungs: heart attack (including fatal cases), inflammation of the fibrous sac surrounding the heart (pericarditis), irregular heart rhythm, chest pain due to reduced blood flow to the heart (angina), low blood pressure, narrowing of the airways causing breathing difficulties, asthma, increased blood pressure in the pulmonary arteries (pulmonary vessels).
• Digestive problems: pancreatitis, peptic ulcer, esophagitis, abdominal bloating, anal fissure, difficulty swallowing, gallbladder inflammation, bile duct obstruction, gastroesophageal reflux (a condition in which stomach acids and contents flow back into the throat).
• Skin, hair, eyes, general: allergic reactions including hypersensitivity, red skin nodules (erythema nodosum), anxiety, confusion, mood swings, decreased libido, fainting, tremors, eye inflammation causing redness or pain, a skin disease characterized by sensitivity, redness, well-defined patches with sudden onset of fever and increased white blood cell count (neutrophilic dermatosis), hearing loss, light sensitivity, visual impairment, increased eye tearing, skin discoloration, inflammation of subcutaneous fat, skin ulcers, skin blisters, nail disorders, hair and hair follicle disorders, hand-foot syndrome, kidney failure, frequent urination, breast enlargement in men, menstrual disorder, general weakness and malaise, reduced thyroid function, loss of balance while walking, osteonecrosis (a disease due to reduced blood supply to bones, which may lead to bone loss and bone death), arthritis, skin swelling anywhere on the body.
• Pain: vein inflammation causing redness, tenderness, and swelling (phlebitis), tendon inflammation.
• Brain: memory loss.
• Tests may show: abnormal blood test results and possible kidney function impairment due to tumor lysis products (tumor lysis syndrome), low blood albumin levels, low lymphocyte levels (a type of white blood cell) in the blood, high blood cholesterol levels, swollen lymph nodes, cerebral hemorrhage, 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 primarily found in the heart and skeletal muscles), increased gamma-glutamyl transferase (an enzyme mainly found in the liver).

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 (myocarditis), 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 (heart disease), inflammation of the tissue lining the heart and lungs (pericarditis and pleuritis), blood clots, blood clots in the lungs (pulmonary embolism).
• Digestive problems: loss of vital nutrients from the digestive tract such as proteins, intestinal obstruction, anal fistula (an abnormal passage from the anus to the surrounding skin), reduced kidney function, diabetes.
• Skin, hair, eyes, general: seizures, optic neuritis (inflammation of the optic nerve that may cause partial or complete vision loss), bluish-purple patches on the skin, abnormally increased thyroid function, thyroid gland inflammation, ataxia (a condition characterized by lack of muscle coordination), difficulty walking, miscarriage, inflammation of blood vessels in the skin (vasculitis), skin fibrosis.
• Brain: stroke, transient episode of neurological dysfunction due to loss of blood flow, facial nerve paralysis, dementia.

Other side effects reported (frequency not known) are:

• inflammation of the lungs;
• bleeding in the stomach or intestines, which may lead to death;
• recurrence (reactivation) of hepatitis B infection in patients with prior hepatitis B (a liver infection);
• a reaction with fever, skin blisters, and mucosal ulceration;
• kidney disease associated with symptoms such as edema and abnormal laboratory test results including protein in the urine and low blood protein levels. Your doctor will monitor some of these effects during treatment.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at the website: http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Dasatinib EG

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 label of the bottle, on the blister or
on the outer packaging after the words “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 medicines 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 Dasatinib EG 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.
• The other components are: Tablet core: microcrystalline cellulose (E460), lactose monohydrate (see section 2 "What you need to know before taking Dasatinib EG"), sodium croscarmellose, hydroxypropylcellulose (E463), magnesium stearate (E470b). Film coating: poly(vinyl alcohol) (E1203), titanium dioxide (E171), talc (E533b), glycerol monostearate (E471), sodium lauryl sulfate.

Description of the appearance of Dasatinib EG and contents of the pack
Dasatinib EG 20 mg: the film-coated tablet is white to almost white, biconvex, round, with "20" engraved on one side and smooth on the other, with a diameter of 6.1 mm.
Dasatinib EG 50 mg: the film-coated tablet is white to almost white, biconvex, oval, with "50" engraved on one side and smooth on the other, measuring 10.9 mm x 5.8 mm.
Dasatinib EG 70 mg: the film-coated tablet is white to almost white, biconvex, round, with "70" engraved on one side and smooth on the other, with a diameter of 8.9 mm.
Dasatinib EG 80 mg: the film-coated tablet is white to almost white, biconvex, triangular, with "80" engraved on one side and smooth on the other, measuring 10.3 mm x 10.0 mm.
Dasatinib EG 100 mg: the film-coated tablet is white to almost white, biconvex, oval, with "100" engraved on one side and smooth on the other, measuring 14.8 mm x 7.2 mm.
Dasatinib EG 140 mg: the film-coated tablet is white to almost white, biconvex, round, with "140" engraved on one side and smooth on the other, with a diameter of 11.8 mm.

Dasatinib EG 20 mg, 50 mg, 70 mg film-coated tablets
Alu-OPA/Alu/PVC blister (perforated blisters for single dose)
High-density polyethylene (HDPE) bottle with a child-resistant polypropylene cap and a plastic (HDPE) container containing silica gel.
Carton containing 60 x 1 or 100 x 1 film-coated tablets in single-dose divisible blisters.
Carton containing a bottle with 60 film-coated tablets.

Dasatinib EG 80 mg, 100 mg, 140 mg film-coated tablets
Alu-OPA/Alu/PVC blister (perforated blisters for single dose)
High-density polyethylene (HDPE) bottle with a child-resistant polypropylene cap and a plastic (HDPE) container containing silica gel.
Carton containing 30 x 1, 60 x 1 or 100 x 1 film-coated tablets in single-dose divisible blisters.
Carton containing a bottle with 30 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder
EG S.p.A. Via Pavia, 6 – 20136 Milan, Italy

Manufacturer
Remedica Ltd, Aharnon Street, Limassol Industrial Estate, 3056 Limassol (Cyprus)
Centrafarm Services B.V., Nieuwe Donk 9, NL-4879 AC Etten-Leur (The Netherlands)
STADA Arzneimittel AG, Stadastrasse 2-18, 61118 Bad Vilbel (Germany)
STADAPHARM GmbH, Feodor-Lynen-Straße 35, 30625 Hannover (Germany)

This medicinal product is authorized in the European Economic Area countries under the following names:
Belgium: Dasatinib EG 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, 140 mg filmomhulde tabletten
Denmark: Dasatinib STADA
Finland: Dasatinib STADA 20, 50, 70, 80, 100 and 140 mg kalvopäällysteiset tabletit
Germany: Dasatinib AL 20 mg Filmtabletten
Dasatinib AL 50 mg Filmtabletten
Dasatinib AL 70 mg Filmtabletten
Dasatinib AL 80 mg Filmtabletten
Dasatinib AL 100 mg Filmtabletten
Dasatinib AL 140 mg Filmtabletten
Italy: Dasatinib EG
Luxembourg: Dasatinib EG 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, 140 mg comprimé pelliculé
The Netherlands: Dasatinib CF 20 mg, filmomhulde tabletten
Dasatinib CF 50 mg, filmomhulde tabletten
Dasatinib CF 70 mg, filmomhulde tabletten
Dasatinib CF 80 mg, filmomhulde tabletten
Dasatinib CF 100 mg, filmomhulde tabletten
Dasatinib CF 140 mg, filmomhulde tabletten
Poland: Dasatinib Stada
Sweden: Dasatinib STADA 20, 50, 70, 80, 100 and 140 mg filmdragerade tabletter