Deferasirox Zentiva

Patient Information Leaflet: Information for the User

DEFERASIROX ZENTIVA 90 mg film-coated tablets, 180 mg film-coated tablets, 360 mg film-coated tablets

Generic Medicine
Please read this leaflet carefully before you or your child 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 or your child 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

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

1. What Deferasirox Zentiva is and what it is used for

What Deferasirox Zentiva is
Deferasirox Zentiva contains an active substance called deferasirox. It is an iron chelator, that is, a medicine used to remove excess iron from the body (also known as iron overload). It binds to excess iron and removes it, primarily through the faeces.

What Deferasirox Zentiva is used for
Patients with various forms of anaemia (for example, thalassaemia, sickle cell anaemia, or myelodysplastic syndromes (MDS)) may require repeated blood transfusions. However, repeated blood transfusions can cause an excess of iron in the body. This occurs because blood contains iron, and the body has no natural way to eliminate the excess iron introduced through blood transfusions. In patients with thalassaemia syndromes who are not receiving blood transfusions, iron overload may also develop over time, primarily due to increased dietary iron absorption in response to low blood cell counts. Over time, excess iron can damage vital organs such as the liver and heart. Medicines called iron chelators are used to remove excess iron and reduce the risk of organ damage.

Deferasirox Zentiva is used to treat iron overload due to frequent blood transfusions in patients with beta-thalassaemia major aged 6 years and older.

Deferasirox Zentiva is also used to treat iron overload when therapy with deferoxamine is contraindicated or inadequate in patients with beta-thalassaemia major who have iron overload due to infrequent blood transfusions, in patients with other forms of anaemia, and in children aged between 2 and 5 years.

Deferasirox Zentiva is also used when therapy with deferoxamine is contraindicated or inadequate for the treatment of patients aged 10 years and older who have iron overload associated with thalassaemia syndromes but who do not require regular blood transfusions.

2. What you need to know before taking Deferasirox Zentiva

Do not take Deferasirox Zentiva if you

• are allergic to deferasirox or to any of the other ingredients of this medicine (listed in section 6). If this applies to you, inform your doctor before taking Deferasirox Zentiva. If you think you may be allergic, consult your doctor.
• have moderate or severe kidney disease.
• are currently taking any other iron-chelating medicine.

Deferasirox Zentiva is not recommended if you

• are in an advanced stage of myelodysplastic syndrome (MDS: reduced production of blood cells by the bone marrow) or have advanced cancer.

Warnings and precautions
Talk to your doctor or pharmacist before taking Deferasirox Zentiva if you:

• have kidney or liver problems.
• have heart problems due to iron overload.
• notice a marked decrease in urine output (a sign of kidney problems).
• develop a severe rash, or experience breathing difficulties, dizziness, or swelling, particularly of the face and throat (signs of a severe allergic reaction; see also section 4 “Possible side effects”).
• develop a combination of any of the following symptoms: rash, red skin, blistering on the lips, eyes or in the mouth, skin peeling, high fever, flu-like symptoms, swollen lymph nodes (signs of a severe skin reaction; see also section 4 “Possible side effects”).
• experience a combination of drowsiness, pain in the upper right abdomen, yellowing or increased yellowing of the skin or eyes, and dark urine (signs of liver problems).
• experience difficulty thinking, remembering information, or solving problems, feel less alert or aware, or feel very drowsy with low energy (signs of high blood ammonium levels, which may be associated with liver or kidney problems; see also section 4 “Possible side effects”).
• vomit blood and/or have black stools.
• experience frequent abdominal pain, particularly after eating or taking Deferasirox Zentiva.
• have frequent heartburn.
• have low platelet or white blood cell counts in blood tests.
• have blurred vision.
• have diarrhoea or vomiting. If any of these situations apply to you, inform your doctor immediately.

Monitoring of treatment with Deferasirox Zentiva
During treatment, you will have regular blood and urine tests. These will monitor the amount of iron in your body (blood ferritin levels) to assess how well Deferasirox Zentiva is working. The tests will also monitor kidney function (blood creatinine levels, presence of protein in urine) and liver function (blood transaminase levels). Your doctor may request a kidney biopsy if significant kidney damage is suspected. To determine the amount of iron in the liver, you may also undergo MRI (magnetic resonance imaging) scans. Your doctor will use these tests to determine the most appropriate dose of Deferasirox Zentiva for you and to decide when treatment should be stopped.
As a precautionary measure, your vision and hearing will be examined annually during treatment.

Other medicines and Deferasirox Zentiva
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This is particularly important for:

• Other iron chelators, which must not be taken with Deferasirox Zentiva.
• Antacids (medicines used to treat heartburn) containing aluminium, which must not be taken at the same time of day as Deferasirox Zentiva.
• Ciclosporin (used to prevent rejection of a transplanted organ or for other conditions such as rheumatoid arthritis or atopic dermatitis).
• Simvastatin (used to lower cholesterol).
• Some painkillers or anti-inflammatory drugs (e.g. aspirin, ibuprofen, corticosteroids).
• Oral bisphosphonates (used to treat osteoporosis).
• Anticoagulant medicines (used to prevent or treat blood clotting).
• Hormonal contraceptives (birth control medicines).
• Bepridil, ergotamine (used for heart conditions and migraines).
• Repaglinide (used to treat diabetes).
• Rifampicin (used to treat tuberculosis).
• Phenytoin, phenobarbital, carbamazepine (used to treat epilepsy).
• Ritonavir (used to treat HIV infection).
• Paclitaxel (used in cancer treatment).
• Theophylline (used to treat respiratory diseases such as asthma).
• Clozapine (used to treat psychiatric disorders such as schizophrenia).
• Tizanidine (used as a muscle relaxant).
• Cholestyramine (used to reduce blood cholesterol levels).
• Busulfan (used as pre-transplant treatment to destroy the original bone marrow before transplantation).
• Midazolam (used to relieve anxiety and/or sleep disorders). Additional monitoring may be needed to check blood levels of some of these medicines.

Elderly (age 65 years and over)
Deferasirox Zentiva can be used in people aged 65 years and over at the same dose as in adults. Elderly patients may experience more side effects (particularly diarrhoea) than younger patients. They should be closely monitored by the doctor for side effects that may require dose adjustment.

Children and adolescents
Deferasirox Zentiva can be used in children and adolescents aged 2 years and over who receive regular blood transfusions, and in children and adolescents aged 10 years and over who do not receive regular blood transfusions. The doctor will adjust the dose according to the patient's growth.
Deferasirox Zentiva is not recommended for children under 2 years of age.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
Deferasirox Zentiva is not recommended during pregnancy unless strictly necessary.
If you are currently using a hormonal contraceptive to prevent pregnancy, you must use an additional or different type of contraception (e.g. a condom), as Deferasirox Zentiva may reduce the effectiveness of hormonal contraceptives.
Breastfeeding is not recommended during treatment with Deferasirox Zentiva.

Driving and using machines
If you feel dizzy after taking Deferasirox Zentiva, do not drive or operate tools or machinery until the dizziness has resolved.

Deferasirox Zentiva contains lactose
If your doctor has informed you that you have an intolerance to certain sugars, contact your doctor before taking this medicine.

3. How to take Deferasirox Zentiva

Treatment with Deferasirox Zentiva will be supervised by a doctor experienced in managing iron overload due to blood transfusions.
Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.

How much Deferasirox Zentiva to take
The dose of Deferasirox Zentiva is based on body weight for all patients. Your doctor will calculate the dose you need and tell you how many tablets to take each day.

• The usual starting daily dose of Deferasirox Zentiva film-coated tablets for patients receiving regular blood transfusions is 14 mg per kilogram of body weight. Your doctor may recommend a higher or lower initial dose depending on your individual treatment needs.
• The usual starting daily dose of Deferasirox Zentiva film-coated tablets for patients not receiving regular blood transfusions is 7 mg per kilogram of body weight.
• Depending on your response to treatment, your doctor may later adjust your dose by increasing or decreasing it.
• The maximum recommended daily dose of Deferasirox Zentiva film-coated tablets is 28 mg per kilogram of body weight for patients receiving regular blood transfusions, 14 mg per kilogram of body weight for adults not receiving regular blood transfusions, and 7 mg per kilogram of body weight for children and adolescents not receiving regular blood transfusions. Deferasirox is also available as "dispersible" tablets. If switching from dispersible tablets to these film-coated tablets, your dose will change. Your doctor will calculate the dose you require and tell you how many film-coated tablets to take each day.

When to take Deferasirox Zentiva

• Take Deferasirox Zentiva once daily, every day, at approximately the same time each day, with a glass of water.
• Take Deferasirox Zentiva film-coated tablets on an empty stomach or with a light meal.

Taking Deferasirox Zentiva at the same time every day will help you remember to take your tablets.
For patients who cannot swallow the tablets whole, Deferasirox Zentiva film-coated tablets may be crushed and administered by mixing the full dose with soft food such as yoghurt or applesauce (apple puree). The food should be consumed immediately and completely. Do not store it for later use.

How long to take Deferasirox Zentiva
Continue taking Deferasirox Zentiva every day for as long as your doctor has instructed. This is a long-term treatment that may last for months or years. Your doctor will monitor your condition regularly to ensure the treatment is effective (see also section 2: “Monitoring of treatment with Deferasirox Zentiva”).
If you have any questions about how long to continue treatment with Deferasirox Zentiva, speak with your doctor.

If you take more Deferasirox Zentiva than you should
If you have taken too much Deferasirox Zentiva, or if someone else has accidentally taken your tablets, contact your doctor or go to hospital immediately for advice. Show the doctor the tablet packaging. Immediate medical treatment may be required. Symptoms may include abdominal pain, diarrhoea, nausea and vomiting, and kidney or liver problems, which may be serious.

If you forget to take Deferasirox Zentiva
If you forget to take a dose, take it as soon as you remember on the same day. Take your next dose at the usual time. Do not take a double dose the next day to make up for the missed tablet(s).

If you stop taking Deferasirox Zentiva
Do not stop taking Deferasirox Zentiva unless your doctor tells you to. If you stop taking it, excess iron will no longer be removed from your body (see also above section “How long to take Deferasirox Zentiva”).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects are mild to moderate and usually disappear after a few days to a few weeks of treatment.
Some side effects may be serious and require immediate medical attention.
These side effects are uncommon (may affect up to 1 in 100 people) or rare (may affect up to 1 in 1,000 people).
Stop taking this medicine and contact your doctor immediately if you

• develop a severe rash, or have difficulty breathing and dizziness or swelling, mainly of the face and throat (signs of a severe allergic reaction).
• experience a combination of any of the following symptoms: rash, red skin, blistering of the lips, eyes or mouth, skin peeling, high fever, flu-like symptoms, swollen lymph nodes (signs of severe skin reactions).
• notice a marked reduction in urine output (sign of kidney problems).
• experience a combination of drowsiness, pain on the right side in the upper abdomen, yellowing or increased yellowing of the skin or eyes, and dark urine (signs of liver problems).
• experience difficulty thinking, remembering information, or solving problems, feel less alert or aware, or feel very drowsy with little energy (signs of high blood ammonium levels, which may be associated with liver or kidney problems and may lead to changes in brain function).
• vomit blood and/or have black stools.
• experience frequent abdominal pain, particularly after eating or taking Deferasirox Zentiva.
• experience frequent heartburn.
• experience partial loss of vision.
• experience severe pain in the upper abdomen (pancreatitis).

Some side effects could become serious.
These side effects are uncommon (may affect up to 1 in 100 people).
Inform your doctor as soon as possible if you

• have blurred or cloudy vision.
• have decreased hearing.

Other side effects
Very common (may affect more than 1 in 10 people)

• Changes in kidney function tests.

Common (may affect up to 1 in 10 people)

• Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain, bloating, constipation, indigestion.
• Rash.
• Headache.
• Changes in liver function tests.
• Itching.
• Changes in urine test (protein in urine). If any of these effects become severe, inform your doctor.

Uncommon (may affect up to 1 in 100 people)

• Dizziness.
• Fever.
• Sore throat.
• Swelling of the arms or legs.
• Change in skin colour.
• Anxiety.
• Sleep disorders.
• Tiredness. If any of these effects occur severely, inform your doctor.

Frequency not known (frequency cannot be estimated from the available data)

• A reduction in the number of cells involved in blood clotting (thrombocytopenia), in the number of red blood cells (worsening of anaemia), in the number of white blood cells (neutropenia), or in the number of all types of blood cells
  (pancytopenia).
• Hair loss.
• Kidney stones.
• Low urine production.
• Tear in the wall of the stomach or intestine, which may be painful and cause nausea.
• Severe pain in the upper abdomen (pancreatitis).
• Increased acidity of the blood.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to 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 . Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Deferasirox Zentiva

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the blister and the outer carton after "Exp.". The expiry date refers to the last day of that month.
• Store below 30 °C. Do not use the pack if it is damaged or shows signs of tampering.
• Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Deferasirox Zentiva contains
The active substance is deferasirox.

• Each film-coated tablet contains 90 mg of deferasirox.
• Each film-coated tablet contains 180 mg of deferasirox.
• Each film-coated tablet contains 360 mg of deferasirox.
  The other ingredients are monohydrate lactose; microcrystalline cellulose (101, 200); crospovidone; povidone K 30; poloxamer 188; anhydrous colloidal silica; magnesium stearate; hypromellose 2910/5; macrogol 4,000; titanium dioxide (E171); talc; aluminium lake containing indigo carmine (E132), only for the 180 mg and 360 mg film-coated tablets.

Description of the appearance of Deferasirox Zentiva and package contents
Deferasirox Zentiva 90 mg film-coated tablets
White to off-white, oblong film-coated tablet with dimensions 11.8 × 5.5 mm.
Deferasirox Zentiva 180 mg film-coated tablets
Blue, oblong film-coated tablet with "Z" embossed on one side, with dimensions 14.8 × 6.85 mm.
Deferasirox Zentiva 360 mg film-coated tablets
Blue to dark blue, oblong film-coated tablets with dimensions 18.65 × 8.6 mm.
Deferasirox Zentiva 90 mg, 180 mg and 360 mg film-coated tablets are available in unit packs containing 30, 90 and 300 tablets (300 tablets only for the 360 mg strength).
Not all pack sizes or strengths may be marketed in your country.

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

Manufacturer
Zentiva k.s.
U kabelovny 130
Praha 10 - Dolní Měcholupy
Czech Republic

LABORMED-PHARMA S.A.
Bd. Theodor Pallady nr. 44B, sector 3
Bucharest, code 032266,
Romania

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Czech Republic, Germany, France, Italy, Slovakia and United Kingdom (Northern Ireland):
Deferasirox Zentiva