Dasatinib Krka

PACKAGE LEAFLET

Package leaflet: information for the patient

Dasatinib Krka 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
Generic medicine
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, ask 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 effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Dasatinib Krka contains the active substance dasatinib. This medicine is used to treat
chronic myeloid leukaemia (CML) in adults, adolescents, and children at least 1 year of
age. Leukaemia 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 begin to
grow uncontrollably. Dasatinib Krka inhibits the growth of these leukaemic cells.
Dasatinib Krka is also used to treat Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (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. Dasatinib Krka inhibits the growth of these leukaemic cells.
If you have any questions about how Dasatinib Krka works or why it has been prescribed for you, consult your doctor.

2. What you should know before taking Dasatinib Krka

Do not take Dasatinib Krka
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 Dasatinib Krka

• if you are taking medicines that thin the blood or prevent clots (see “Other medicines and Dasatinib Krka”)
• if you have or have had liver or heart problems
• if you start experiencing breathing difficulties, chest pain, or cough while taking Dasatinib Krka: this could be a symptom 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 Dasatinib Krka 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 Dasatinib Krka, contact your doctor. These may be signs of damage to blood vessels known as thrombotic microangiopathy (TMA).

Your doctor should regularly monitor your clinical condition to check whether Dasatinib Krka is
having the desired effect. In addition, you will have regular blood tests while taking
Dasatinib Krka.

Children and adolescents
Do not give this medicine to children under one year of age. Experience with Dasatinib Krka in
this age group is limited. Bone growth and development in children taking Dasatinib Krka
will be closely monitored.

Other medicines and Dasatinib Krka
Inform your doctor if you are taking, have recently taken, or might take any other
medicines.
Dasatinib Krka is mainly metabolized by the liver. Some medicines may interfere with
the effect of Dasatinib Krka when taken at the same time as Dasatinib Krka.

These medicines must not be used with Dasatinib Krka:

• ketoconazole, itraconazole – antifungal medicines
• erythromycin, clarithromycin, telithromycin – antibiotics
• ritonavir – an antiviral medicine
• phenytoin, carbamazepine, phenobarbital – treatments for epilepsy
• rifampicin – a treatment for tuberculosis
• famotidine, omeprazole – 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 Krka.
Inform your doctor if you are taking medicines that thin the blood or prevent clots.

Dasatinib Krka with food and drink
Do not take Dasatinib Krka with grapefruit or grapefruit juice.

Pregnancy and breastfeeding
If you are pregnant or suspect you may be pregnant, inform your doctor immediately. Dasatinib
Krka must not be used during pregnancy unless strictly necessary. Your doctor will discuss
with you the potential risks of taking Dasatinib Krka during pregnancy.
Both men and women taking Dasatinib Krka 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
Dasatinib Krka.

Driving and using machines
If you experience side effects such as dizziness or blurred vision, exercise particular
caution when driving or operating machinery.

Dasatinib Krka contains lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this
medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially “sodium-free”.

3. How to take Dasatinib Krka

Dasatinib Krka will only be prescribed by a doctor experienced in the treatment of leukemia. Take this medicine exactly as your doctor has instructed. If you have any doubts, consult your doctor or pharmacist. Dasatinib Krka 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 chronic myeloid leukemia (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. Dasatinib is administered orally once daily as either dasatinib tablets or dasatinib oral suspension powder. Dasatinib tablets are not recommended for patients weighing less than 10 kg. For patients weighing less than 10 kg and 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), a change in dose may occur; therefore, do not switch from one formulation to the other on your own. Your doctor will determine the appropriate formulation and dose based on body weight, any side effects, and response to treatment. The initial dose of Dasatinib Krka for children is calculated according to body weight as follows:
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 Dasatinib Krka 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.
How to take Dasatinib Krka
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. Dasatinib Krka tablets may be taken with or without food.
Special precautions for handling Dasatinib Krka
It is unlikely that Dasatinib Krka tablets will break. However, if a tablet does break, individuals other than the patient must wear gloves when handling Dasatinib Krka.
How long to take Dasatinib Krka
Take Dasatinib Krka daily for as long as your doctor instructs. Make sure you take Dasatinib Krka for the entire duration prescribed.
If you take more Dasatinib Krka 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 Krka
Do not take a double dose to make up for a 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, or fainting
• if unexpected bleeding or bruising occurs without injury
• if you find blood in your vomit, stools, or urine, or if your stools are black
• if signs of infection such as fever or severe chills occur
• if you develop 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: 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 (during or after stopping treatment), abdominal pain
• Laboratory and instrumental tests may show: low platelet count, low white blood cell count (neutropenia), anemia, 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, altered taste, 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, 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 edema
• 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 membrane (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 arteries (blood vessels) of the lungs
• Digestive system problems: inflammation of the pancreas, peptic ulcer, inflammation of the esophagus, bloated abdomen, tear in the skin of the anal canal, difficulty swallowing, inflammation of the gallbladder, blockage of bile ducts, gastroesophageal 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 increased white blood cell count (neutrophilic dermatosis), hearing loss, light sensitivity, impaired vision, increased eye tearing, skin pigmentation disorders, inflammation of the fatty tissue under the skin, skin ulcers, blisters on the skin, nail disorders, hair and hair follicle disorders, hand-foot syndrome, kidney failure, increased frequency of urination, 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, swelling of the skin anywhere in 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 tumor lysis products (tumor lysis syndrome), low levels of albumin in the blood, low levels of lymphocytes (a type of white blood cells) in the blood, high cholesterol levels in the blood, swollen lymph nodes, brain hemorrhage, irregularities in the heart's electrical activity, heart enlargement, liver inflammation, protein in the 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)

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 artery disease (of the heart), 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 gastrointestinal 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, bluish-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, spontaneous abortion, 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 edema 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 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 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 Krka

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging 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 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 Krka 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: monohydrate lactose (200); microcrystalline cellulose (101 and 102);
sodium croscarmellose, hydroxypropylcellulose (MW 80,000), magnesium stearate.
Coating: monohydrate lactose; hypromellose (15 mPas); titanium dioxide (E171); triacetin.
(See Section 2 “Dasatinib Krka contains lactose and sodium”).

Description of the appearance of Dasatinib Krka and package contents
Dasatinib Krka 20 mg: the film-coated round tablet (tablet) is white to off-white, biconvex, with a diameter of approximately 5.6 mm, marked with “D7SB” on one side and “20” on the other side.
Dasatinib Krka 50 mg: the film-coated oval tablet (tablet) is white to off-white, biconvex, with a length of approximately 11 mm and a width of approximately 6.0 mm, marked with “D7SB” on one side and “50” on the other side.
Dasatinib Krka 70 mg: the film-coated round tablet (tablet) is white to off-white, biconvex, with a diameter of approximately 9.1 mm, marked with “D7SB” on one side and “70” on the other side.
Dasatinib Krka 80 mg: the film-coated triangular tablet (tablet) is white to off-white, biconvex, with a length of approximately 10.4 mm and a width of approximately 10.6 mm, marked with “D7SB” on one side and “80” on the other side.
Dasatinib Krka 100 mg: the film-coated oval tablet (tablet) is white to off-white, biconvex, with a length of approximately 15.1 mm and a width of approximately 7.1 mm, marked with “D7SB” on one side and “100” on the other side.
Dasatinib Krka 140 mg: the film-coated round tablet (tablet) is white to off-white, biconvex, with a diameter of approximately 11.7 mm, marked with “D7SB” on one side and “140” on the other side.

Dasatinib Krka at all strengths is available in packages containing:

• 30 or 60 film-coated tablets in non-perforated blisters.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturers
Synthon Hispania S.L., Castelló, 1, Polígono las Salinas, 08830 Sant Boi de Llobregat, Spain
Synthon BV, Microweg 22, 6545 CM Nijmegen, Netherlands
KRKA d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
KRKA-FARMA d.o.o., V. Holjevca 20/E, 10450 Jastrebarsko, Croatia

Local representative for Italy
KRKA Farmaceutici Milano S.r.l. - Italy

This medicinal product is authorized in the European Economic Area countries under the following names: