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

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so you can read it again if you need to.
• If you have any doubts, you should 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 any side effects not listed in this leaflet, they should tell 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 infection. In people with CML, white blood cells called granulocytes grow out of control. Daruph stops 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 stops the growth of these leukemia cells.

If you have any questions about how Daruph works or why it has been prescribed for you, you should ask your doctor.

2. Important information before taking Daruph

When not to take Daruph

Warnings and precautions

Before starting treatment with Daruph, you should discuss it with your doctor or pharmacist.

Children and adolescents

Daruph should not be used in children under 1 year of age. Data on the use of dasatinib in this age group are limited. In children taking Daruph, growth and bone development should be closely monitored.

Daruph and other medicines

You should 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.

The following medicines should not be taken 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 to treat epilepsy.
• Rifampicin - this is a medicine used to treat tuberculosis.
• St. John's Wort - a herbal medicine available without a prescription, used to treat depression and other conditions (also known as Hypericum perforatum).

You should 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, you should take them 2 hours after taking Daruph to get the best results.

You should tell your doctor if you are taking medicines that thin the blood or prevent blood clots.

Taking Daruph with food and drink

You should 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. Your 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.

You should inform your doctor if you are breastfeeding. You should not breastfeed while taking Daruph.

Driving and using machines

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

Daruph contains lactose and sodium

If you have been diagnosed with intolerance to some sugars, you should tell your doctor before taking Daruph.

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

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

Daruph will only be prescribed by a doctor experienced in treating leukemia. You should always take Daruph as directed by your doctor. If you are unsure, you should 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 with chronic phase CML is 79 mg once daily.

The recommended initial dose of Daruph for adult patients with accelerated phase or blast crisis CML, or with Ph+ ALL, is 111 mg once daily.

The dose 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 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 oral suspension should be used. When switching from one formulation to another (i.e., tablets and oral suspension), the dose may change, so 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 dose of Daruph in children under 1 year of age.

Based on the response to treatment, the doctor may decide to increase or decrease the dose, or even interrupt treatment for a short time. To take higher or lower doses, it may be necessary to use a combination of tablets of different strengths.

How to take Daruph

Tablets should be taken at the same time every day. The tablets should be swallowed whole.

Do not crush, divide, or chew them. Do not take crushed 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

Daruph should be taken every day until your doctor decides to stop it.

You should make sure that Daruph is taken for as long as your doctor has prescribed.

Taking a higher dose of Daruph than recommended

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

Missing a dose of Daruph

You should not take a double dose to make up for a missed tablet. You should take the next dose at the usual time.

If you have any further doubts about taking the medicine, you should consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Daruph 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 vomit blood, have black stools, or blood in your urine.
• if you experience symptoms of infection such as fever, chills.
• if you experience fever, mouth pain, throat pain, blistering, or peeling of the skin and 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, viral infection (including cytomegalovirus (CMV)), 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 pain, muscle spasms.
• 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 sac around 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 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 formation of painful, red nodules 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 painful, red, distinct spots on the skin with sudden onset of fever and increased white blood cell count (neutrophilic dermatosis), hearing loss, sensitivity to light, vision disturbances, increased tearing, skin discoloration, inflammation of the fatty tissue under the skin, skin ulcers, blistering, nail disorders, hair disorders, hand and foot disorders, 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, skin swelling 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 in the blood, high cholesterol levels in the blood, enlarged lymph nodes, bleeding into 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: malabsorption of essential nutrients such as proteins, intestinal obstruction, anal fistula, kidney function disorders, 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, walking difficulties, miscarriage, skin blood vessel inflammation, skin scarring.
• 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 bone growth; growth retardation.

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

• Pneumonia.
• 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.
• Damaged 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 any side effects not listed in this leaflet, you should tell 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.

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 the medicine.

5. How to store Daruph

The medicine should be stored 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 stated.

There are no special precautions for storing the medicine.

Medicines should not be disposed of via wastewater or household waste. You should 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.
• The 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.

Package size: Daruph 16 mg, 40 mg, 55 mg film-coated tablets: 56 and 60 film-coated tablets.

Package size: Daruph 63 mg, 79 mg, 111 mg film-coated tablets: 28 and 30 film-coated tablets.

Not all package 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, you should contact the local representative of the marketing authorization holder:

Zentiva Polska Sp. z.o.o.

ul. 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: