Daruph

Patient Information Leaflet

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, 111 mg film-coated tablets

dasatinib
Please read all of this leaflet carefully before you take this medicine because it contains important information for you.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may 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:
What Daruph is and what it is used for
What you need to know before taking 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 to treat chronic myeloid leukemia (CML) in adults, adolescents, and children aged at least 1 year. Leukemia is a cancer of the white blood cells. Normally, white blood cells help the body fight infections. In people with CML, white blood cells called granulocytes grow uncontrollably. Daruph inhibits the growth of these leukemic cells.
Daruph is also used to treat Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in adults, adolescents, and children aged at least 1 year, and for the treatment of lymphoid blast phase CML in adults who have not responded to prior therapies. In individuals with ALL, white blood cells called lymphocytes multiply rapidly and live longer than normal. Daruph inhibits the growth of these leukemic cells.
If you have any questions about how Daruph works or why it has been prescribed for you, consult your doctor.

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

• 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 Daruph if:

• you are taking medicines that thin the blood or prevent blood clots (see "Other medicines and Daruph")
• you have or have had liver or heart problems
• you start experiencing breathing difficulties, chest pain, or cough while taking Daruph: 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
• you have had or may currently have hepatitis B infection. This is because dasatinib 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
• you develop bruising, bleeding, fever, fatigue, or confusion while taking Daruph, contact your doctor. These may be signs of damage to blood vessels known as thrombotic microangiopathy (TMA)
• your doctor has told you that you have reduced stomach acidity (achlorhydria/hypochlorhydria). The dosage of Daruph may need to be adjusted.

Your doctor will regularly monitor your clinical condition to check whether Daruph is having the desired effect. Additionally, you will have regular blood tests while taking Daruph.

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

Other medicines and Daruph
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 can interfere with the effect of Daruph when taken at the same time.

The following medicines must not be used with Daruph:

• Ketoconazole, itraconazole – antifungal medicines
• Erythromycin, clarithromycin, telithromycin – antibiotics
• Ritonavir – an antiviral medicine
• Phenytoin, carbamazepine, phenobarbital – treatments for epilepsy
• Rifampicin – a treatment for tuberculosis
• St. John’s wort – a herbal preparation available without prescription, used for 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 Daruph.
If you are taking acid-reducing medicines such as omeprazole, to achieve the best results, take this medicine at least 2 hours after taking Daruph.
Inform your doctor if you are taking medicines that thin the blood or prevent 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, inform your doctor immediately. Daruph must not be used during pregnancy unless strictly necessary. Your doctor will discuss with you the potential risks of taking Daruph during pregnancy.
Both men and women taking Daruph 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 Daruph.

Driving and using machines
If you experience side effects such as dizziness or blurred vision, take special care when driving or operating machinery.

Daruph contains lactose and sodium
If your doctor has told you that you have an intolerance to certain sugars, discuss this with your doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially “sodium-free”.

How to take Daruph
Do not switch from taking Daruph tablets to other dasatinib tablets without first talking to your doctor. The dosage of Daruph tablets differs from that of other dasatinib-containing medicines.
Daruph will only be prescribed by a doctor experienced in the treatment of leukemia.
Always take this medicine exactly as your doctor has instructed. If you are unsure, consult your doctor or pharmacist. Daruph is prescribed for adults and children aged at least 1 year.
The recommended initial dose for adult patients with chronic phase CML is 79 mg once daily.
The recommended initial dose for adult patients with accelerated phase CML, blast phase CML, or Ph+ ALL is 111 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 in the form of film-coated tablets or oral suspension powder. Daruph film-coated tablets are not recommended for patients weighing less than 10 kg. In patients weighing less than 10 kg and in patients unable to swallow tablets, the oral suspension powder should be used. When switching between formulations (i.e., between tablets and oral suspension), the dose may change; therefore, do not switch from one to the other without medical advice. Your doctor will determine the appropriate formulation and dose based on body weight, possible side effects, and response to treatment. The initial dose of Daruph for children is calculated according to 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 brief interruption of treatment. For higher or lower doses, you may need to take combinations of tablets with different strengths.

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

Special precautions for handling Daruph
It is unlikely that Daruph tablets will break. If they do, individuals other than the patient must wear gloves when handling Daruph.

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

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

If you forget to take Daruph
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.

Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody experiences 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 appear.
• If you experience fever, mouth or throat pain, blisters, or skin and/or mucosal peeling.

Contact your doctor immediately if you notice any of the above effects.

Side effects very common (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 interruption of 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.

Side effects common (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 pulmonary pressure, cough.
• Digestive system problems: loss of appetite, altered taste, bloating or distension of the abdomen, colitis, 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 flashes, 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 spasms.
• Laboratory and instrumental tests may show: fluid around the heart, fluid in the lungs, arrhythmia, febrile neutropenia, gastrointestinal bleeding, elevated blood uric acid levels.

Side effects uncommon (may affect up to 1 in 100 people):

• Heart and lungs: heart attack (including fatal cases), inflammation of the sac surrounding the heart (pericarditis), irregular heartbeat, 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.
• Digestive system problems: pancreatitis, peptic ulcer, esophagitis, bloated abdomen, anal fissure, difficulty swallowing, cholecystitis, bile duct obstruction, gastroesophageal reflux (a condition where stomach acid and contents flow back into the throat).
• Skin, hair, eyes, general: allergic reactions including hypersensitivity, red nodules on the skin (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, impaired vision, increased eye tearing, skin discoloration, inflammation of subcutaneous fat tissue, skin ulcers, skin blisters, nail disorders, hair and nail abnormalities, hand-foot syndrome, kidney failure, frequent urination, breast enlargement in men, menstrual disorders, general weakness and malaise, reduced thyroid function, loss of balance while walking, osteonecrosis (a disease caused by 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.
• Laboratory and instrumental 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), high blood cholesterol levels, swollen lymph nodes, intracranial hemorrhage, heart electrical activity irregularities, enlarged heart, 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), elevated gamma-glutamyltransferase (an enzyme mainly found in the liver).

Side effects rare (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 group 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, inflammation of the tissue lining the heart and lungs, blood clots, pulmonary embolism.
• Digestive system problems: loss of vital nutrients from the gastrointestinal tract (e.g., 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 (which may cause partial or complete vision loss), blue-purple skin patches, abnormally increased thyroid function, thyroid gland inflammation, ataxia (a condition associated with lack of muscle coordination), difficulty walking, miscarriage, skin blood vessel inflammation (vasculitis), skin fibrosis.
• Brain: stroke, transient neurological episode due to loss of blood flow, facial nerve paralysis, dementia.
• Immune system: severe allergic reaction.
• Musculoskeletal and connective tissue: delayed fusion of the rounded ends forming joints (epiphyses); slowed or delayed growth.

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

• Pneumonia.
• Bleeding in the stomach or intestines that may lead to death.
• Reactivation of hepatitis B infection if you have previously had hepatitis B (a liver infection).
• A reaction with fever, skin blisters, and mucosal ulceration.
• Kidney disease with symptoms including edema and abnormal laboratory results such as protein in urine and low blood protein levels.
• Blood vessel damage known as thrombotic microangiopathy (TMA), including reduced red blood cell count, reduced platelet count, and blood clot formation.

Your doctor will monitor some of these effects during treatment.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via 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 stated on the blister or 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 no longer used. 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.
Other components are:
Tablet core: lactose monohydrate, microcrystalline cellulose, hydroxypropylcellulose, sodium croscarmellose, magnesium stearate.
Film coating: hypromellose, propylene glycol, titanium dioxide, iron oxide yellow (E172) (only in Daruph 55 mg film-coated tablets).

Description of the appearance of Daruph and contents of the pack
Daruph 16 mg film-coated tablets
Round, white to off-white film-coated tablets, imprinted with "15.8" on one side, 5.5 mm in diameter.
Daruph 40 mg film-coated tablets
Round, white to off-white film-coated tablets, imprinted with "39.5" on one side, 7 mm in diameter.
Daruph 55 mg film-coated tablets
Round, light yellow to yellow film-coated tablets, imprinted with "55.3" on one side, 7 mm in diameter.
Daruph 63 mg film-coated tablets
Round, white to off-white film-coated tablets, imprinted with "63.2" on one side, 8.5 mm in diameter.
Daruph 79 mg film-coated tablets
Round, white to off-white film-coated tablets, imprinted with "79.0" on one side, 9.5 mm in diameter.
Daruph 111 mg film-coated tablets
Round, white to off-white film-coated tablets, imprinted with "110.6" on one side, 11 mm in diameter.
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 Authorization 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 medicine is authorized in the European Economic Area member states under the following names:
Germany, Hungary, Italy, Poland, Romania, Slovakia, Sweden: Daruph