DEFERASIROX SIGILLATA

Patient Information Leaflet: Information for the User

Deferasirox Sigillata 125 mg dispersible tablets, 250 mg dispersible tablets, 500 mg dispersible tablets

Deferasirox
Generic medicine
Please read this leaflet carefully before taking this medicine, as 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 others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

What Deferasirox Sigillata is
Deferasirox Sigillata 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). Deferasirox binds to excess iron and removes it, primarily eliminating it through the faeces.

What Deferasirox Sigillata is used for
In patients with various forms of anaemia (for example, thalassaemia, sickle cell anaemia, or myelodysplastic syndromes (MDS)), repeated blood transfusions may be necessary. However, these can lead to an excess of iron in the body. This occurs because blood contains iron, and the body does not have a natural way to remove the excess iron introduced by 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 a low number of blood cells.

Over time, excess iron can damage important organs such as the liver and heart. Medicines called iron chelators are used to eliminate excess iron and reduce the risk of organ damage.

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

Deferasirox Sigillata is also used to treat iron overload when deferoxamine therapy 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 Sigillata is also used when deferoxamine therapy 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 blood transfusions.

2. What you need to know before taking Deferasirox Sigillata

Do NOT take Deferasirox Sigillata

• 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 Sigillata. If you think you might be allergic, consult your doctor.
• if you have moderate or severe kidney disease.
• if you are currently taking any other iron-chelating medicine.

Deferasirox Sigillata is NOT recommended

• if you have advanced myelodysplastic syndrome (MDS: reduced production of blood cells by the bone marrow) or advanced-stage cancer.

Warnings and precautions
Talk to your doctor or pharmacist before taking Deferasirox Sigillata:

• if you have kidney or liver problems,
• if you have a heart condition due to iron overload,
• if you notice a marked decrease in urine output (a sign of kidney problems),
• if you 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”),
• if you develop any combination of the following symptoms: rash, red skin, blistering on the lips, eyes or mouth, skin peeling, high fever, flu-like symptoms, swollen lymph nodes (signs of a severe skin reaction; see also section 4, “Possible side effects”),
• if you experience a combination of drowsiness, pain in the upper right part of the abdomen, yellowing or increased yellowing of the skin or eyes, and dark urine (signs of liver problems),
• if you experience difficulty thinking, remembering information, or solving problems, if you 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”),
• if you vomit blood and/or have black stools,
• if you experience frequent abdominal pain, especially after eating or taking deferasirox,
• if you have frequent heartburn,
• if blood tests show low platelet or white blood cell counts,
• if you have blurred vision,
• if you have diarrhoea or vomiting. If any of these situations apply to you, inform your doctor immediately.

Monitoring during treatment with Deferasirox Sigillata
During treatment, you will have regular blood and urine tests. These will monitor the amount of iron in your body (blood ferritin level) to assess how well Deferasirox Sigillata is working. The tests will also check kidney function (blood creatinine level, 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 magnetic resonance imaging (MRI) scans. Your doctor will use these test results to determine the most appropriate dose of Deferasirox Sigillata 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 Sigillata
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 Sigillata,
• antacids (medicines used to treat heartburn) containing aluminium, which must NOT be taken at the same time of day as Deferasirox Sigillata,
• cyclosporine (used to prevent rejection of a transplanted organ or for other conditions such as rheumatoid arthritis or atopic dermatitis),
• simvastatin (used to lower cholesterol),
• certain 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 (medicines for birth control),
• 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),
• colestyramine (used to reduce blood cholesterol levels),
• busulfan (used as part of pre-transplant treatment to destroy the original bone marrow before transplantation),
• midazolam (used to relieve anxiety and/or sleep disorders).

Additional monitoring may be required to check blood levels of some of these medicines.

Elderly patients (age 65 years or older)
Deferasirox Sigillata can be used in patients aged 65 years or older 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 their doctor for side effects that may require dose adjustment.

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

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

Driving and using machines
If you feel dizzy after taking Deferasirox Sigillata, do not drive or operate tools or machinery until you feel normal again.

Deferasirox Sigillata contains lactose and sodium
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per dispersible tablet, i.e. essentially ‘sodium-free’.

3. How to take Deferasirox Sigillata

Treatment with Deferasirox Sigillata will be monitored by a doctor experienced in the treatment of iron overload caused by blood transfusions.
Take this medicine exactly as your doctor has instructed you. If you have any doubts, consult your doctor or pharmacist.

How much Deferasirox Sigillata to take
The dose of Deferasirox Sigillata 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 Sigillata dispersible tablets for patients receiving regular blood transfusions is 20 mg per kilogram of body weight. Your doctor may recommend a higher or lower starting dose depending on the need for individualized treatment.
• The usual starting daily dose of Deferasirox Sigillata dispersible tablets for patients not receiving regular blood transfusions is 10 mg per kilogram of body weight.
• Depending on your response to treatment, your doctor may subsequently adjust the dose by increasing or decreasing it.
• The maximum recommended daily dose of Deferasirox Sigillata dispersible tablets is 40 mg per kilogram of body weight for patients receiving regular blood transfusions, 20 mg per kilogram of body weight for adult patients not receiving regular blood transfusions, and 10 mg per kilogram of body weight for children and adolescents not receiving regular blood transfusions.

Deferasirox is also available as “film-coated tablets”. If you are switching from film-coated tablets or granules to these dispersible tablets, a dose adjustment will be necessary.

When to take Deferasirox Sigillata

• Take Deferasirox Sigillata once daily, every day, at approximately the same time each day with some water.
• Take Deferasirox Sigillata dispersible tablets on an empty stomach.
• Therefore, wait at least 30 minutes before eating any food. Taking Deferasirox Sigillata at the same time every day will also help you remember when to take the tablets.

How to take Deferasirox Film-coated Tablets:  Drop the tablet(s) into a glass of water, apple juice, or orange juice (100–200 ml).  Stir until the tablet(s) have completely dissolved. The liquid in the glass will appear cloudy.  Drink the entire contents of the glass. Then add a small amount of water or juice to the residue left in the glass, stir, and drink again. DO NOT dissolve the tablets in carbonated beverages or milk. DO NOT chew, divide, or break the tablets. DO NOT swallow the tablets whole.

How long to take Deferasirox Sigillata
Continue taking Deferasirox Sigillata every day for the duration your doctor has prescribed. This is a long-term treatment, which may last for months or years. Your condition will be monitored regularly by your doctor to ensure the treatment is effective (see also section 2: “Monitoring of treatment with Deferasirox Sigillata”).
If you have any questions about how long you should take Deferasirox Sigillata, speak with your doctor.

If you take more Deferasirox Sigillata than you should
If you have taken too much Deferasirox Sigillata, or if someone else has accidentally taken your tablets, contact your doctor or hospital immediately for advice. Show the doctor the tablet packaging. Medical treatment may be necessary. Symptoms such as abdominal pain, diarrhoea, nausea and vomiting, and problems with the kidneys or liver, which may be serious, could occur.

If you forget to take Deferasirox Sigillata
If you forget to take a dose, take it as soon as you remember during that day. Take your next dose at the usual time. DO NOT take a double dose the next day to make up for the forgotten tablet(s).

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. Most side effects are mild to moderate and usually disappear after a period of treatment ranging from a few days to a few weeks.
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).

• If you develop a severe skin rash, or have difficulty breathing and dizziness or swelling mainly of the face and throat (signs of a severe allergic reaction),
• If you experience a combination of any of the following symptoms: skin 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),
• If you notice a marked reduction in urine output (sign of kidney problem),
• If you experience a combination of drowsiness, pain in the right upper part of the abdomen, yellowing or increased yellowing of the skin or eyes, and dark urine (signs of liver problems),
• If you experience difficulty thinking, remembering information, or solving problems, if you 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),
• If you vomit blood and/or have black stools,
• If you experience frequent abdominal pain, particularly after eating or taking Deferasirox Sigillata,
• If you experience frequent heartburn,
• If you experience partial loss of vision,
• If you experience severe pain in the upper part of the abdomen (pancreatitis), stop taking this medicine and contact your doctor immediately.

Some side effects could become serious.
These side effects are uncommon.

• If you have blurred or cloudy vision,
• If you have decreased hearing, contact your doctor as soon as possible. Other side effects Very common (may affect more than 1 in 10 people)
• Abnormal 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
• Abnormal liver function tests
• Itching
• Abnormal urine test (protein in urine) If any of these side effects become severe, inform your doctor.

Uncommon (may affect up to 1 in 100 people)

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

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

• A reduction in the number of blood 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 part of the abdomen (pancreatitis)
• Increased acidity of the blood.

Reporting of side effects
If you get any side effect, including those not listed in this leaflet, talk to 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.

5. How to store Deferasirox Sigillata

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 and the outer carton after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
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 Sigillata contains

• The active substance is deferasirox.
  Deferasirox Sigillata 125 mg: Each dispersible tablet contains 125 mg of deferasirox.
  Deferasirox Sigillata 250 mg: Each dispersible tablet contains 250 mg of deferasirox.
  Deferasirox Sigillata 500 mg: Each dispersible tablet contains 500 mg of deferasirox.
• The other components are monohydrate lactose, microcrystalline cellulose, crospovidone type A (E1202), povidone K30 (E1201), sodium lauryl sulfate, anhydrous colloidal silica and magnesium stearate.

Description of the appearance of Deferasirox Sigillata and package contents
Deferasirox Sigillata 125 mg dispersible tablets are white to almost white, round, flat tablets with bevelled edges, embossed with "77" on one side and "438" on the other. The approximate diameter of each tablet is 12 mm.
Deferasirox Sigillata 250 mg dispersible tablets are white to almost white, round, flat tablets with bevelled edges, embossed with "77" on one side and "498" on the other. The approximate diameter of each tablet is 15 mm.
Deferasirox Sigillata 500 mg dispersible tablets are white to almost white, round, flat tablets with bevelled edges, embossed with "77" on one side and "440" on the other. The approximate diameter of each tablet is 20 mm.
Deferasirox Sigillata 125 mg, 250 mg and 500 mg dispersible tablets are available in blister packs containing 30 dispersible tablets.

Marketing Authorization Holder
Sigillata Limited
Block A
15 Castleforbes Square
Sheriff Street
Dublin 1
Ireland

Manufacturer
Pliva Hrvatska d.o.o.
Prilaz Baruna Filipovića 25
Zagreb
Grad Zagreb
10000 Croatia

This medicinal product is authorized in the European Economic Area countries under the following names:
Denmark: Deferasirox Sigillata
Italy: Deferasirox Sigillata