Exferana

Package leaflet: Information for the patient

Exferana 90 mg film-coated tablets
Exferana 180 mg film-coated tablets
Exferana 360 mg film-coated tablets
Deferasirox
Please read this leaflet carefully before taking this medicine, as it contains important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Exferana is and what it is used for

What Exferana is
Exferana contains an active substance called deferasirox. It is an iron-chelating agent,
i.e. a medicine used to remove excess iron (also known as iron overload)
from the body. Exferana binds and removes excess iron, which is then excreted
mainly in the faeces.
What Exferana is used for
Frequent blood transfusions may be necessary for patients with various types of anaemia
(e.g. thalassaemia, sickle cell disease or myelodysplastic syndromes).
However, repeated blood transfusions can lead to accumulation of excess iron. This occurs
because blood contains iron, and the body lacks natural mechanisms to eliminate excess
iron received during transfusions. In patients with non-transfusion-dependent thalassaemia syndromes,
iron overload may also develop over time, primarily due to increased iron absorption from food,
as a response to low red blood cell count. Over time, excess iron may damage vital organs such as the liver and heart.
To remove excess iron and reduce the risk of organ damage, iron-chelating medicines are used.
Exferana is used in the treatment of chronic iron overload due to frequent blood transfusions in patients with severe beta-thalassaemia aged 6 years and older.
Exferana is also used in the treatment of chronic iron overload when deferoxamine therapy is contraindicated or inappropriate, in patients with severe beta-thalassaemia with iron overload due to infrequent blood transfusions, in patients with other types of anaemia, and in patients aged 2 to 5 years.
Exferana is also used, when deferoxamine therapy is contraindicated or inadequate, in the treatment of patients aged 10 years and older with iron overload associated with non-transfusion-dependent thalassaemia syndromes.

2. Important information before taking Exferana
When not to use Exferana

• if the patient is allergic to deferasirox or to any of the other ingredients of this medicine (listed in section 6). If the patient has such hypersensitivity, they must inform their doctor before taking Exferana. If the patient suspects they may be allergic, they should consult their doctor;
• if the patient has moderate or severe kidney impairment;
• if the patient is currently taking any other iron-chelating medicines.

Use of Exferana is not recommended

• if the patient has advanced myelodysplastic syndrome (reduced blood cell production by the bone marrow) or advanced malignant tumour.

Warnings and precautions
Before starting Exferana, discuss with your doctor or pharmacist if:

• the patient has kidney or liver disease;
• the patient has heart problems caused by iron overload;
• the patient notices a significant decrease in urine output (a sign of kidney disease);
• the patient develops a severe rash, breathing difficulties, dizziness, or swelling mainly of the face and throat (symptoms of a severe allergic reaction; see also section 4 "Possible side effects");
• the patient develops any combination of the following symptoms: rash, red skin, blistering of the lips, eyes or mouth, skin peeling, high fever, flu-like symptoms, swollen lymph nodes (symptoms of a severe skin reaction; see also section 4 "Possible side effects");
• the patient develops drowsiness, pain in the upper right part of the abdomen, yellowing or worsening yellow discoloration of the skin or eyes, and dark urine (symptoms of liver disease);
• the patient experiences difficulties with thinking, remembering information, or problem-solving, becomes less alert or aware, or feels drowsy along with lack of energy (symptoms of high blood ammonia levels, which may be related to liver or kidney disorders; see also section 4 "Possible side effects");
• the patient vomits blood and/or passes black stools;
• the patient frequently experiences abdominal pain, especially after eating or taking Exferana;
• the patient frequently experiences heartburn;
• the patient has blood tests showing low platelet or white blood cell counts;
• the patient experiences blurred vision;
• the patient has diarrhoea or vomiting.

If any of the above apply to the patient, they should inform their doctor immediately.
Monitoring of Exferana treatment
During treatment, the patient will undergo regular blood and urine tests. These are intended to
monitor the amount of iron in the body (serum ferritin levels) to assess how Exferana is working.
Blood tests also monitor kidney function (serum creatinine levels, presence of protein in urine) and liver function (increased aminotransferase activity in blood). The treating doctor may order a kidney biopsy if significant kidney damage is suspected. The patient may also undergo MRI (magnetic resonance imaging) to determine liver iron concentration. The treating doctor will consider the results of these tests when determining the optimal dose of Exferana for the individual patient and when deciding whether to discontinue Exferana.
As a precaution, annual eye and hearing examinations will be performed during treatment.

Exferana and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take. These include in particular:

• other iron-chelating medicines, which must not be taken with Exferana;
• antacids (medicines used to treat heartburn) containing aluminium, which should not be taken at the same time of day as Exferana;
• cyclosporine (used to prevent organ transplant rejection or to treat other diseases such as rheumatoid arthritis or atopic dermatitis);
• simvastatin (used to reduce cholesterol levels);
• painkillers or anti-inflammatory medicines (e.g. aspirin, ibuprofen, corticosteroids);
• oral bisphosphonates (used to treat osteoporosis);
• anticoagulants (used to prevent or treat excessive blood clotting);
• hormonal contraceptives (birth control medicines);
• bepridil, ergotamine (used for heart conditions or 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 to treat cancer);
• 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 before receiving a transplant to destroy existing bone marrow prior to transplantation).

The doctor may order additional tests to monitor blood levels of some of these medicines.

Elderly patients (aged 65 years and older)
Exferana may be used in patients aged 65 years and older at the same doses as in other adult patients. Elderly patients may experience more adverse reactions (especially diarrhoea) than younger patients. Patients in this age group should be closely monitored by their treating doctor to detect possible adverse reactions that may require dose adjustment.

Children and adolescents
Exferana may 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. As the patient grows, the doctor will adjust the dose of the medicine.
Exferana is not recommended for children under 2 years of age.

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor before using this medicine.
Exferana is not recommended during pregnancy unless there is a clear medical need for treatment.
If the patient is currently taking oral contraceptives or using contraceptive patches to prevent pregnancy, it is necessary to use an additional contraceptive method or a different type of contraception (e.g. condoms), as deferasirox may reduce the effectiveness of oral and transdermal contraceptives.
Breastfeeding is not recommended during treatment with Exferana.

Driving and operating machinery
If the patient experiences dizziness while taking Exferana, they should not drive or operate machinery until they feel well again.

Exferana contains lactose
If the patient has been previously diagnosed with intolerance to certain sugars, they should consult their doctor before taking this medicine.

Exferana contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means the medicine is considered "sodium-free".

3. How to take Exferana

Treatment with Exferana will be supervised by a doctor experienced in managing patients with iron overload due to blood transfusions.
This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.

How much Exferana to take
In all patients, the dose of Exferana is based on body weight. Your doctor will calculate the required dose and inform you how many tablets to take per day.

• The usual starting daily dose of deferasirox, film-coated tablets, in patients receiving regular blood transfusions is 14 mg per kilogram of body weight. Depending on individual needs, your doctor may prescribe a higher or lower initial dose.
• In patients not receiving regular blood transfusions, the usual starting daily dose of deferasirox, film-coated tablets, is 7 mg per kilogram of body weight.
• Depending on the response to treatment, your doctor may adjust the dose at a later stage, either increasing or decreasing it.
• The maximum recommended daily dose of deferasirox, film-coated tablets, is:
  – 28 mg per kilogram of body weight in patients receiving regular blood transfusions,
  – 14 mg per kilogram of body weight in adult patients not receiving regular blood transfusions,
  – 7 mg per kilogram of body weight in children and adolescents not receiving regular blood transfusions.

Deferasirox is also available as dispersible tablets for oral suspension. If a patient switches from the dispersible tablets to the film-coated tablets, the dose must be adjusted accordingly.

When to take Exferana

• Exferana should be taken once daily, every day, at approximately the same time each day, with a small amount of water.
• Exferana film-coated tablets should be taken either on an empty stomach or with a light meal.

Taking Exferana at the same time each day will help you remember to take your medicine.
For patients who cannot swallow the tablets whole, Exferana film-coated tablets may be crushed and the entire dose mixed with a semi-solid food, such as yogurt or apple puree (applesauce). The mixture should be consumed immediately and not stored for later use.

How long to take Exferana
You should continue taking Exferana every day for as long as your doctor recommends. This is a long-term treatment that may last several months or years. Your doctor will regularly monitor your health to assess whether the treatment is achieving the desired effects (see also section 2: "Monitoring treatment with Exferana").
If you have any questions about the duration of treatment with Exferana, please consult your doctor.

Taking more Exferana than recommended
If you take more Exferana than prescribed, or if someone else accidentally takes the tablets, seek immediate medical advice from your doctor or go to the nearest hospital. Bring the medicine packaging with you. Immediate medical treatment may be necessary. The patient may experience symptoms such as abdominal pain, diarrhoea, nausea and vomiting, and kidney or liver problems, which may be serious.

Missing a dose of Exferana
If you miss a dose, take it as soon as possible on the same day. Take the next dose at your usual time. Do not take a double dose the next day to make up for the missed tablet(s).

Stopping Exferana
Do not stop taking Exferana unless instructed by your doctor. If treatment is stopped, excess iron will no longer be removed from the body (see also section "How long to take Exferana").

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Most adverse reactions are mild to moderate in intensity and usually resolve within a few days or weeks of treatment.
Some adverse reactions may be serious and require immediate medical attention.
These adverse reactions occur uncommonly (may affect up to 1 in 100 patients) or rarely (may affect up to 1 in 1000 patients).

• If the patient develops severe rash, difficulty breathing, dizziness, or swelling, mainly of the face and throat (symptoms of a severe allergic reaction);
• if the patient experiences any combination of the following symptoms: rash, red skin, blistering of the lips, eyes or mouth, skin peeling, high fever, flu-like symptoms, swollen lymph nodes (symptoms of severe skin reactions);
• if the patient notices a significant decrease in the amount of urine passed (symptom of kidney disease);
• if the patient simultaneously experiences drowsiness, pain in the upper right part of the abdomen, yellowing or worsening yellow discoloration of the skin or eyes, and dark urine (symptoms of liver disease);
• if the patient has difficulty thinking, remembering information, or solving problems, becomes less alert or aware, or feels drowsy along with lack of energy (symptoms of high blood ammonia levels, which may be related to liver or kidney disorders and may lead to changes in brain function);
• if the patient vomits blood and/or passes black stools;
• if the patient frequently experiences abdominal pain, especially after eating or taking Exferana;
• if the patient frequently experiences heartburn;
• if the patient experiences partial loss of vision;
• if the patient experiences sudden severe pain in the upper abdomen (pancreatitis);
  the medicine should be discontinued immediately and the doctor should be informed without delay.

Some adverse reactions may become severe.
These adverse reactions occur uncommonly.

• If blurred or cloudy vision occurs;
• if hearing impairment occurs;
  the doctor should be informed as soon as possible.

Other adverse reactions
Very common (may affect more than 1 in 10 patients)

• Abnormal kidney function test results.

Common (may affect up to 1 in 10 patients)

• Gastrointestinal disturbances such as nausea, vomiting, diarrhoea, abdominal pain, bloating, constipation, dyspepsia
• Rash
• Headache
• Abnormal liver function test results
• Itching
• Abnormal urine test result (protein in urine)
  If any of these symptoms are severe, the doctor should be informed.

Uncommon (may affect up to 1 in 100 patients)

• Dizziness
• Fever
• Sore throat
• Swelling of arms and legs
• Change in skin pigmentation
• Restlessness
• Sleep disturbances
• Fatigue
  If any of these symptoms are severe, the doctor should be informed.

Frequency not known (cannot be estimated from available data)

• Decreased number of platelets involved in blood clotting (thrombocytopenia), decreased number of red blood cells (worsening of anaemia), decreased number of white blood cells (neutropenia), or decreased number of all types of blood cells (pancytopenia)
• Hair loss
• Kidney stones
• Low volume of urine output
• Perforation of the stomach or intestinal wall, which may cause pain and nausea
• Acute pain in the upper abdomen (pancreatitis)
• Abnormal blood acidity

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, the doctor, pharmacist, or nurse should be informed. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration 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
Adverse reactions can also be reported to the marketing authorization holder. Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Exferana

• Keep this medicine out of sight and reach of children.
• Do not use this medicine after the expiry date stated on the blister and carton after EXP and Expiry date (EXP). The expiry date refers to the last day of the stated month.
• Do not use this medicine if you notice any signs of damage or deterioration of the packaging.
• Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Exferana contains
The active substance is deferasirox.
Each Exferana 90 mg coated tablet contains 90 mg of deferasirox.
Each Exferana 180 mg coated tablet contains 180 mg of deferasirox.
Each Exferana 360 mg coated tablet contains 360 mg of deferasirox.

The other ingredients are:
Tablet core: microcrystalline cellulose (types 101 and 102), povidone K-30, crospovidone (types A and B), poloxamer 188, colloidal anhydrous silica, magnesium stearate.
Coating substances: hypromellose (E 464), lactose monohydrate, titanium dioxide (E 171), triacetin, indigo carmine aluminium lake (E 132).

What Exferana looks like and contents of the pack
Exferana is available as coated tablets. The coated tablets are oval and biconvex.

• Exferana 90 mg coated tablets: Light blue, oval, biconvex coated tablets of approximately 10 mm x 6 mm in size, with the imprint "D7FX" on one side and "90" on the other side.
• Exferana 180 mg coated tablets: Blue, oval, biconvex coated tablets of approximately 13 mm x 7 mm in size, with the imprint "D7FX" on one side and "180" on the other side.
• Exferana 360 mg coated tablets: Dark blue, oval, biconvex coated tablets of approximately 15 mm x 9 mm in size, with the imprint "D7FX" on one side and "360" on the other side.

Unit packs containing 30 or 90 coated tablets. The blister foil may be perforated or non-perforated.
Not all pack sizes or strengths may be marketed.

Marketing Authorisation Holder
VIPHARM S.A.
ul. A. i F. Radziwiłłów 9
05-850 Ożarów Mazowiecki
Poland

Manufacturers
Synthon Hispania S.L.
Calle Castello 1
08830 Sant Boi de Llobregat
Barcelona
Spain
Synthon BV
Microweg 22
6545 CM Nijmegen
The Netherlands

This medicinal product is authorised in the European Economic Area countries under the following names:
Netherlands Exferana 90 mg, filmomhulde tabletten
Exferana 180 mg filmomhulde tabletten
Exferana 360 mg filmomhulde tabletten
Czech Republic Exferana
Hungary Exferana 90 mg filmtabletta
Exferana 180 mg filmtabletta
Exferana 360 mg filmtabletta
Poland Exferana
Slovakia Exferana 90 mg
Exferana 180 mg
Exferana 360 mg