DARUPH 16 mg Film-Coated Tablets

Зміст інструкції

1. Daruph 16 mg film-coated tablets, 40 mg film-coated tablets, 55 mg film-coated tablets, 63 mg film-coated tablets, 79 mg film-coated tablets

Daruph 16 mg film-coated tablets, 40 mg film-coated tablets, 55 mg film-coated tablets, 63 mg film-coated tablets, 79 mg film-coated tablets

Daruph 111 mg film-coated tablets
dasatinib

Read 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 pass it on to others,
even if their symptoms are the same as yours, as it may be harmful.
If you get any side effects, even those not listed in this leaflet, tell your doctor or
pharmacist. See section 4.

Contents of this leaflet:
What Daruph is and what it is used for
What you need to know before you take Daruph
How to take Daruph
Possible side effects
How to store Daruph
Contents of the pack and other information

What Daruph is and what it is used for
Daruph contains the active substance dasatinib.
This medicine is used for the treatment of chronic myeloid leukaemia
(CML) in adults, adolescents and children aged 1 year and over. Leukaemia is
a cancer of the white blood cells. White blood cells normally help the body to
fight infections. In people with CML, white blood cells called
granulocytes start to grow out of control. Daruph inhibits the growth of these cells
leukaemic cells.
Daruph is also used for the treatment of Philadelphia chromosome-positive (Ph+)
acute lymphoblastic leukaemia (ALL) in adults, adolescents and children
aged 1 year and over and lymphoid blast phase CML in adults who have not
benefited from previous therapies. In people with ALL, white blood cells called
lymphocytes multiply very quickly and live for a long time. Daruph inhibits the
growth of these leukaemic cells.
If you have any questions about how Daruph works or why it has been
prescribed for you, ask your doctor.

What you need to know before you take Daruph
Do not take Daruph

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

Warnings and precautions
Talk to your doctor or pharmacist before taking Daruph if
you are taking medicines that thin the blood or prevent blood clots (see "Other
medicines and Daruph")
you have liver or heart problems, or have had them
you start to have difficulty breathing, chest pain or cough while taking Daruph:
this could be a sign of fluid build-up in the lungs or chest
(which may be more common in patients aged 65 years or older) or may be due to changes in the blood vessels that supply the lungs
you have ever had or may have an ongoing hepatitis B infection. This is because
dasatinib may cause hepatitis B to become active again, which can in some cases be
life-threatening. Patients will be carefully checked by their doctor for signs of
this infection before starting treatment
you develop bruising, bleeding, fever, tiredness and confusion while taking
Daruph, contact your doctor. This may be a sign of damage to blood vessels
known as thrombotic microangiopathy (TMA)
you have been told by your doctor that you have reduced stomach acid
(achlorhydria/hypochlorhydria). The dose of Daruph may need to be adjusted.
Your doctor will need to monitor your condition regularly to check if
Daruph is having the desired effect. You will also have regular blood tests while taking Daruph.

Children and adolescents
Do not give this medicine to children under 1 year of age. Experience with the use of
dasatinib in this age group is limited. The growth and bone development of children
taking Daruph will be carefully monitored.

Other medicines and Daruph
Tell your doctor if you are taking, have recently taken or might take
any other medicines.
Dasatinib is broken down mainly by the liver. Some medicines can interfere
with the effect of Daruph when taken at the same time.
These medicines must not be used with Daruph:
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.
St John's Wort - a herbal remedy available without prescription used for the treatment of depression and other
conditions (also known as Hypericum perforatum).
Do not take medicines that neutralise stomach acid (antacids such as
aluminium hydroxide or magnesium hydroxide) within 2 hours before or 2 hours after
taking Daruph.
If you are using medicines that block stomach acid such as omeprazole, to get the
best results, this medicine should be taken 2 hours after taking
Daruph.
Tell your doctor if you are taking medicines that thin the blood or prevent
blood clots.

Daruph with food and drink
Do not take Daruph with grapefruit or grapefruit juice.

Pregnancy and breastfeeding
If you are pregnant or suspect you may be pregnant, tell your doctor immediately.
Daruph should not be used during pregnancy unless it is absolutely
necessary. Your doctor will discuss the potential risks of taking Daruph
during pregnancy with you.
Both men and women taking Daruph should use effective contraception during treatment.
If you are breastfeeding, tell your doctor. Breastfeeding must be stopped during
treatment with Daruph.

Driving and using machines
If you experience side effects such as dizziness or blurred vision, be careful when
driving and using machines.

Daruph contains lactose and sodium
If you have been told by your doctor that you have an intolerance to some sugars, talk to your
doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, that is to say
essentially “sodium-free”.

How to take Daruph
Do not switch from taking Daruph tablets to other dasatinib tablets without
talking to your doctor. The dose of Daruph tablets is different from that of
other medicines containing dasatinib.
Daruph will only be prescribed by a doctor who is experienced in treating leukaemia.
Always take this medicine exactly as your doctor has told you. If you have
any doubts, ask your doctor or pharmacist. Daruph is prescribed for adults and children
aged 1 year and over.
The recommended starting dose in adult patients with chronic phase CML is 79 mg once
daily.
The recommended starting dose in adult patients with accelerated phase or blast phase CML or with Ph+ ALL is 111 mg once daily.
The dose in children with chronic phase CML or Ph+ ALL is based on body weight.
Dasatinib is taken by mouth once daily as film-coated tablets or oral suspension.
Daruph film-coated tablets are not recommended in patients weighing less than 10 kg. In patients weighing less than 10
kg and in patients who cannot swallow the tablets, the oral suspension should be used. When switching between formulations (i.e. between tablets and
oral suspension) there may be a change in dose, therefore do not
switch between them. Your doctor will decide the right formulation and dose based on
weight, any side effects and response to treatment. The starting dose of Daruph
for children is calculated based on body weight, as shown below:
There is no recommended dose of Daruph for children under 1 year of age.
Depending on how you respond to treatment, your doctor may recommend a
higher or lower dose, or even a temporary interruption of treatment. For higher or lower doses you may need to take combinations of tablets of different strengths.

How to take Daruph
Take the tablets at the same time each day. Swallow the tablets whole without
crushing, breaking or chewing them. Do not take dissolved tablets. You cannot be certain
of getting the correct dose if you crush, break, chew or disperse the tablets. The
tablets of Daruph can be taken with or without food.

Special precautions for handling Daruph
It is unlikely that Daruph tablets will break. If this does happen, people
other than the patient should wear gloves when handling Daruph.

How long to take Daruph
Take Daruph daily until your doctor tells you to stop. Make sure you
take Daruph for as long as it has been prescribed for you.

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

If you forget to take Daruph
Do not take a double dose to make up for a missed tablet. Take the
next dose as scheduled at the usual time.
If you have any questions about using this medicine, ask your doctor or pharmacist.

Possible side effects
Like all medicines, this medicine can cause side effects, although
not everyone gets them.

The following can 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 experience signs of infection such as fever, chills.
If you experience fever, mouth sores or sore throat, blisters or peeling of the
skin and/or mucous membranes.

Contact your doctor immediatelyif you notice any of the above effects.
Very common side effects (may affect more than 1 in 10 people):

• Infections (including bacterial, viral and fungal infections).
• Heart and lungs: shortness of breath.
• Problems of the digestive system: diarrhea, feeling or state of unwellness (nausea, vomiting).
• Skin, hair, eyes, general: skin 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, presence of fluid in the lungs.

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, weak myocardium, high blood pressure, increased pressure in the lungs, cough.
• Problems of the digestive system: loss of appetite, altered taste, bloating or distension 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 noise in the ears, hair loss, excessive sweating, eye disorders (including blurred vision and visual disturbances), dry eye, 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, high uric acid levels in the blood.

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

• Heart and lungs: heart attack (including fatal ones), 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 can cause difficulty breathing, asthma, increased blood pressure in the arteries (blood vessels) of the lungs.
• Problems of the digestive system: 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 the bile ducts, gastro-esophageal reflux (a condition where stomach acids and other stomach contents rise 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 condition characterized by sensitivity, redness, well-defined patches with sudden onset of fever and increased white blood cell count (neutrophilic dermatosis), hearing loss, sensitivity to light, impaired vision, increased tearing of the eyes, skin color disturbances, inflammation of the subcutaneous fatty tissue, skin ulcers, blisters on the skin, nail disorders, hair and hair disorders, hand-foot syndrome, kidney failure, frequent urination, breast enlargement in men, menstrual disorder, general weakness and malaise, decreased thyroid function, loss of balance while walking, osteonecrosis (a disease due to reduced blood flow to the bones, which can cause bone loss and bone death), arthritis, swelling of the skin anywhere in the body.
• Pain: inflammation of the veins which can cause redness, sensitivity and swelling, tendon inflammation.
• Brain: memory loss.
• Laboratory and instrumental tests may show: fluid around the heart, fluid in the lungs, arrhythmia, febrile neutropenia, gastrointestinal bleeding, high uric acid levels in the blood.

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

• Heart and lungs: enlargement of the right ventricle of the heart, inflammation of the heart muscle, a set of conditions resulting from blockage of 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.
• Problems of the digestive system: loss of vital nutrients from the digestive tract, such as proteins, intestinal obstruction, anal fistula (an abnormal fissure from the anus to the skin around the anus), reduced kidney function, diabetes.
• Skin, hair, eyes, general: convulsions, inflammation of the optic nerve which can cause partial or complete loss of vision, blue-violet 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 the blood vessels of the skin, fibrosis of the skin.
• Brain: stroke, temporary episode of neurological dysfunction caused by loss of blood flow, facial nerve paralysis, dementia.
• Immune system: severe allergic reaction.
• Musculoskeletal and connective tissue: delay in the fusion of the rounded ends that form the joints (epiphyses); slowed or delayed growth.
• Other side effects reported with frequency not known(cannot be estimated based on available data):

Pneumonia.

Bleeding in the stomach or intestines which can cause death.

Recurrence (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 ulceration of the mucous membranes.

Kidney disease with symptoms including edema and abnormal laboratory results such as the presence of protein in the urine and low protein levels in the blood.

Damage to blood vessels known as thrombotic microangiopathy (TMA), including decreased red blood cell count, decreased platelets and formation of blood clots.

The doctor will monitor some of these effects during treatment.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on the safety of this medicine.

How to store Daruph
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 blister or the box after Expiry Date. 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 water or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

Contents of the pack and other information
What Daruph contains
The active substance is dasatinib. Each film-coated tablet contains 15.8 mg, 39.5 mg, 55.3 mg, 63.2 mg, 79.0 mg or 110.6 mg of dasatinib.
The other ingredients are: Tablet core: lactose monohydrate, microcrystalline cellulose, hydroxypropylcellulose, sodium croscarmellose, magnesium stearate.
Film coating: hypromellose, propylene glycol, titanium dioxide, yellow iron oxide (E172) (only Daruph 55 mg film-coated tablets).

Description of Daruph and contents of the pack
Daruph 16 mg film-coated tablets
Round film-coated tablets of white to off-white color imprinted with “15,8” on one side with a diameter of 5.5 mm.
Daruph 40 mg film-coated tablets
Round film-coated tablets of white to off-white color imprinted with “39,5” on one side with a diameter of 7 mm.
Daruph 55 mg film-coated tablets
Round film-coated tablets of light yellow to yellow color imprinted with “55,3” on one side with a diameter of 7 mm.
Daruph 63 mg film-coated tablets
Round film-coated tablets of white to off-white color imprinted with “63,2” on one side with a diameter of 8.5 mm.
Daruph 79 mg film-coated tablets
Round film-coated tablets of white to off-white color imprinted with “79.0” on one side with a diameter of 9.5 mm.
Daruph 111 mg film-coated tablets
Round film-coated tablets of white to off-white color imprinted with “110,6” on one side with a diameter of 11 mm.
Daruph is packaged in OPA/Alu/PVC//Alu blisters.
Pack sizes: Daruph 16 mg, 40 mg, 55 mg film-coated tablets: 56 and 60 film-coated tablets. Daruph 63 mg, 79 mg, 111 mg film-coated tablets: 28 and 30 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva Italia S.r.l.
Via P. Paleocapa, 7
20121 Milano, Italy

Manufacturer
Zentiva, k.s.
U Kabelovny 130
102 37 Prague 10
Czech Republic
Pharmacare Premium Ltd
HHF003 Hal Far Industrial Estate
Hal Far Birzebbugia
BBG3000 Malta

This medicinal product is authorised in the Member States of the European Economic Area
with the following denominations:
Germany, Hungary, Italy, Poland, Romania, Slovakia, Sweden Daruph