Daruph

Leaflet accompanying the packaging: information for the user

Daruph, 16 mg, film-coated tablets

Daruph, 40 mg, film-coated tablets

Daruph, 55 mg, film-coated tablets

Daruph, 63 mg, film-coated tablets

Daruph, 79 mg, film-coated tablets

Daruph, 111 mg, film-coated tablets

Dasatinib

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm them, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Daruph and what is it used for
• 2. Important information before taking Daruph
• 3. How to take Daruph
• 4. Possible side effects
• 5. How to store Daruph
• 6. Contents of the pack and other information

1. What is Daruph and what is it used for

Daruph contains the active substance dasatinib. This medicine is used to treat chronic myeloid leukemia (CML) in adults, adolescents, and children aged 1 year and older. Leukemia is a cancer of white blood cells. White blood cells normally help the body fight infections. In people with CML, white blood cells called granulocytes grow out of control. Daruph inhibits the growth of these leukemia cells.
Daruph is also used to treat acute lymphoblastic leukemia (ALL) with Philadelphia chromosome positive (Ph+ ALL) in adults, adolescents, and children aged 1 year and older, as well as lymphoblastic blast crisis in CML in adults who have not responded to previous treatment. In people with acute lymphoblastic leukemia, white blood cells called lymphocytes multiply too quickly and live too long. Daruph inhibits the growth of these leukemia cells.
If you have any questions about how Daruph works or why it has been prescribed for you, ask your doctor.

2. Important information before taking Daruph

When not to take Daruph

Warnings and precautions

Before starting treatment with Daruph, discuss this with your doctor or pharmacist.

Children and adolescents

Do not give this medicine to children under 1 year of age. There is limited data on the use of dasatinib in this age group. In children taking Daruph, growth and bone development should be closely monitored.

Daruph and other medicines

Tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Dasatinib is mainly broken down in the liver. Certain medicines may affect the action of Daruph if taken at the same time.
Do not take the following medicines with Daruph:

• Ketoconazole, itraconazole - these are antifungal medicines.
• Erythromycin, clarithromycin, telithromycin - these are antibiotics.
• Ritonavir - this is an antiviral medicine.
• Phenytoin, carbamazepine, phenobarbital - these are medicines used in epilepsy.
• Rifampicin - this is a medicine used in tuberculosis.
• St. John's Wort - a herbal medicine available without a prescription, used to treat depression and other conditions (also known as Hypericum perforatum).

Do not take medicines that neutralize stomach acid (such as aluminum hydroxide or magnesium hydroxide) within 2 hours before or 2 hours after taking Daruph.
If you are taking medicines that reduce stomach acid production, such as omeprazole, to get the best results, take this medicine 2 hours after taking Daruph.
Tell your doctor if you are taking medicines that thin the blood or prevent blood clots.

Taking Daruph with food and drink

Do not take Daruph with grapefruit or grapefruit juice.

Pregnancy and breastfeeding

Women who are pregnant or think they may be pregnant should inform their doctor. Daruph should not be given to pregnant women unless it is absolutely necessary. The doctor will discuss the risks that may occur during treatment with Daruph during pregnancy.
It is recommended that both men and women use effective contraception during treatment with Daruph.
Inform your doctor if you are breastfeeding. Do not breastfeed while taking Daruph.

Driving and using machines

If you experience side effects such as dizziness and vision disturbances, be careful when driving or operating machinery.

Daruph contains lactose and sodium

If you have been told that you have an intolerance to some sugars, inform your doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means it is essentially 'sodium-free'.

3. How to take Daruph

Do not switch from one dasatinib-containing product to another without consulting your doctor. The tablet strength of Daruph is different from other dasatinib-containing products.

Daruph will be prescribed only by a doctor experienced in the treatment of leukemia. This medicine should always be taken as directed by your doctor. If you are unsure, consult your doctor or pharmacist. Daruph is intended for adults and children aged 1 year and older.
The recommended initial dose of Daruph for adult patients in the chronic phase of CML is 79 mg once daily.
The recommended initial dose of Daruph for adult patients in the accelerated phase or blast crisis of CML, or with Ph+ ALL, is 111 mg once daily.
The dosage of Daruph for children with CML in the chronic phase or Ph+ ALL is determined based on body weight.
Dasatinib is given orally once daily in the form of film-coated tablets or powder for oral suspension. It is not recommended to use Daruph film-coated tablets in patients with a body weight of less than 10 kg. In patients with a body weight of less than 10 kg and in patients who are unable to swallow tablets, the powder for oral suspension should be used. When switching from one formulation to another (i.e., tablets and powder for oral suspension), the dose may need to be adjusted, and you should not switch from one formulation to another. Based on the patient's body weight, side effects, and response to treatment, the doctor will determine the appropriate formulation and dose. The initial dose of Daruph in children is calculated based on body weight, as follows:
There are no recommendations for the use of Daruph in children under 1 year of age.
Depending on the response to treatment, the doctor may decide to increase or decrease the dose, or even interrupt treatment temporarily. To take higher or lower doses, it may be necessary to use a combination of tablets of different strengths.

How to take Daruph

Take the tablets at the same time every day. Swallow the tablets whole. Do not crush, divide, or chew them. Do not take crushed or divided tablets.
If the tablets are crushed, divided, chewed, or crushed, it is not certain that the patient has received the correct dose. Daruph tablets can be taken with or without food.

Special precautions for handling Daruph

It is unlikely that Daruph tablets will be damaged. However, if this happens, people handling Daruph should wear protective gloves.

How long to take Daruph

Take Daruph every day until your doctor decides to stop it. Make sure you take Daruph for as long as your doctor has prescribed.

Taking a higher dose of Daruph than prescribed

If you accidentally take more tablets than prescribed, inform your doctor immediately, as you may need medical attention.

Missing a dose of Daruph

Do not take a double dose to make up for a missed tablet. Take the next dose at the usual time.
If you have any further questions about taking 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 symptoms may indicate serious side effects:

• if you experience chest pain, difficulty breathing, coughing, and fainting.
• if you experience unexpected bleeding or bruising without previous injury.
• if you have blood in your vomit, stool, or urine, or if your stool is black.
• if you experience symptoms of infection such as fever, severe chills.
• if you experience fever, mouth pain, or throat pain, blistering, or peeling of the skin and (or) mucous membranes. You should immediately inform your doctorif you experience any of the above symptoms.

Very commonside effects (may affect more than 1 in 10 people):

• Infections (including bacterial, viral, and fungal infections).
• Heart and lungs: shortness of breath.
• Gastrointestinal disorders: diarrhea, nausea, or vomiting.
• Skin, hair, eyes, general symptoms: skin rash, fever, facial swelling, hand and foot swelling, headache, feeling tired or weak, bleeding.
• Pain: muscle pain (during or after treatment), abdominal pain.
• Laboratory tests may show: low platelet count, low white blood cell count (neutropenia), anemia, fluid around the lungs.

Commonside effects (may affect up to 1 in 10 people):

• Infections: pneumonia, cytomegalovirus (CMV) infection, upper respiratory tract infections, severe blood or tissue infections (including rare cases that were fatal).
• Heart and lungs: rapid heartbeat, irregular heartbeat, heart failure, weakening of the heart muscle, high blood pressure, increased blood pressure in the lungs, coughing.
• Gastrointestinal disorders: loss of appetite, taste disorders, bloating, colitis, constipation, heartburn, mouth ulcers, weight gain, weight loss, gastritis.
• Skin, hair, eyes, general symptoms: tingling, itching, dry skin, acne, skin inflammation, ringing in the ears, hair loss, excessive sweating, vision disturbances (including blurred vision), dry eye, bruising, depression, insomnia, flushing, dizziness, injuries (bruises), loss of appetite, drowsiness, generalized swelling.
• Pain: joint pain, muscle weakness, chest pain, hand and foot pain, chills, muscle stiffness and joint stiffness.
• Laboratory tests may show: fluid around the heart, fluid in the lungs, heart rhythm disturbances, low white blood cell count (neutropenia) with fever, gastrointestinal bleeding, high uric acid levels in the blood.

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

• Heart and lungs: heart attack (including fatal cases), inflammation of the heart sac, 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 pulmonary arteries.
• Gastrointestinal disorders: pancreatitis, stomach ulcers, esophagitis, abdominal swelling, anal fissure, difficulty swallowing, gallbladder inflammation, bile duct obstruction, gastroesophageal reflux disease (a condition in which stomach acid and other stomach contents flow back into the throat).
• Skin, hair, eyes, general symptoms: allergic reactions, including the development of tender, red lumps on the skin (erythema nodosum), anxiety, disorientation, mood changes, decreased libido, fainting, tremors, eye inflammation, which can cause redness or pain, a skin condition characterized by the presence of tender, red, distinct patches on the skin with sudden onset of fever and increased white blood cell count (neutrophilic dermatosis), hearing loss, sensitivity to light, vision disturbances, increased tear production, skin discoloration, skin inflammation, blistering, nail disorders, hair disorders, disorders of the hands and feet, kidney failure, frequent urination, breast enlargement in men, menstrual disorders, general weakness and discomfort, decreased thyroid function, loss of balance while walking, bone death (a condition characterized by decreased blood flow to the bones, leading to bone loss and death), joint inflammation, swelling of the skin at any site on the body.
• Pain: vein inflammation, which can cause redness, pain, and swelling, tendon inflammation.
• Brain: memory loss.
• Laboratory tests may show: abnormal blood test results and possible kidney function disorders caused by tumor breakdown products (tumor lysis syndrome), low albumin levels in the blood, low lymphocyte count (a type of white blood cell) in the blood, high cholesterol levels in the blood, enlarged lymph nodes, bleeding in the brain, abnormal heart rhythm, enlarged heart, liver inflammation, protein in the urine, increased creatine phosphokinase activity (an enzyme mainly found in the heart, brain, and skeletal muscles), increased troponin activity (an enzyme mainly found in the heart and skeletal muscles), increased gamma-glutamyltransferase activity (an enzyme mainly found in the liver), milky fluid around the lungs (chylous effusion).

Rareside effects (may affect up to 1 in 1000 people):

• Heart and lungs: enlargement of the right heart chamber, heart muscle inflammation, a condition characterized by blockage of blood flow to the heart muscle (acute coronary syndrome), cardiac arrest (stoppage of blood flow from the heart), coronary artery disease (heart), inflammation of the tissue covering the heart and lungs, blood clots, blood clots in the lungs.
• Gastrointestinal disorders: loss of essential nutrients from the digestive tract, such as proteins, intestinal obstruction, anal fistula, kidney damage, diabetes.
• Skin, hair, eyes, general symptoms: seizures, optic nerve inflammation, which can cause total or partial loss of vision, blue-purple spots on the skin, hyperthyroidism, thyroid inflammation, lack of coordination, difficulty walking, abortion, skin vasculitis, skin fibrosis.
• Brain: stroke, transient neurological disturbances due to lack of blood flow, facial nerve paralysis, dementia.
• Immune system: severe allergic reaction.
• Musculoskeletal and connective tissue disorders: delayed closure of the growth plates (ends of bones that form joints); slowed or delayed growth.

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

• Pneumonitis.
• Bleeding in the stomach or intestines, which can lead to death.
• Recurrence (reactivation) of hepatitis B virus infection (liver infection) in patients who have had the disease in the past.
• A reaction characterized by fever, blistering of the skin, and mucous membrane ulcers.
• Kidney disease symptoms, including swelling and abnormal laboratory test results, such as 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 platelet count, and blood clot formation.

During treatment, your doctor will check for the above side effects.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309.
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder or its representative.
Reporting side effects will help to gather more information on the safety of this medicine.

5. How to store Daruph

Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister or carton after the words "EXP". The expiry date refers to the last day of the month.
There are no special precautions for storing the medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Daruph contains

• The active substance of Daruph 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 ingredients are: Tablet core:lactose monohydrate, microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, magnesium stearate. Tablet coating: hypromellose, propylene glycol, titanium dioxide (E171), yellow iron oxide (E172) (only for Daruph 55 mg film-coated tablets).

What Daruph looks like and contents of the pack

Daruph 16 mg film-coated tablets
The film-coated tablet is white or almost white, round, with the imprint "15.8" on one side and a diameter of 5.5 mm.
Daruph 40 mg film-coated tablets:
The film-coated tablet is white or almost white, round, with the imprint "39.5" on one side and a diameter of 7 mm.
Daruph 55 mg film-coated tablets:
The film-coated tablet is light yellow or yellow, round, with the imprint "55.3" on one side and a diameter of 7 mm.
Daruph 63 mg film-coated tablets:
The film-coated tablet is white or almost white, round, with the imprint "63.2" on one side and a diameter of 8.5 mm.
Daruph 79 mg film-coated tablets:
The film-coated tablet is white or almost white, round, with the imprint "79.0" on one side and a diameter of 9.5 mm.
Daruph 111 mg film-coated tablets:
The film-coated tablet is white or almost white, round, with the imprint "110.6" on one side and a diameter of 11 mm.
Daruph is packaged in an OPA/Aluminum/PVC/Aluminum blister pack.
Pack size: Daruph 16 mg, 40 mg, 55 mg film-coated tablets: 56 and 60 film-coated tablets.
Pack size: 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, k.s.
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer

Zentiva, k.s.
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Pharmacare Premium Ltd.

HHF003 Hal Far Industrial Estate
Hal Far Birzebbugia
BBG 3000, Malta

To obtain more detailed information, contact the local representative of the marketing authorization holder:

Zentiva Polska Sp. z.o.o.
Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00

This medicine is authorized for marketing in the Member States of the European Economic Area under the following names:

Germany, Hungary, Italy, Poland, Romania, Slovakia, Sweden: Daruph
Date of last revision of the leaflet: