Exferana

Package leaflet: Information for the patient

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 you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, 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.

Table of contents

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
(for example, 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 has no natural way of eliminating excess iron
received during transfusions. In patients with non-transfusion-dependent thalassaemia syndromes,
iron overload may also develop over time, primarily due to increased absorption of iron 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 agents are used.
Exferana is used to treat chronic iron overload due to frequent blood transfusions in patients with severe beta-thalassaemia aged 6 years and older.
Exferana is also used to treat chronic iron overload when deferoxamine therapy is contraindicated or inappropriate, in patients with severe beta-thalassaemia who have 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, for 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 take Exferana

• if you are allergic to deferasirox or any of the other ingredients of this medicine (listed in section 6). If you have such hypersensitivity, you must inform your doctor before taking Exferana. If you suspect you may be allergic, consult your doctor;
• if you have moderate or severe kidney impairment;
• if you are currently taking any other iron-chelating medicines.

Use of Exferana is not recommended

• if you have advanced myelodysplastic syndrome (reduced blood cell production by the bone marrow) or advanced malignant neoplasm.

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

• you have kidney or liver disease;
• you have heart problems caused by iron overload;
• you notice a significant decrease in the amount of urine passed (a sign of kidney disease);
• you develop 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");
• you experience 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");
• you experience simultaneously drowsiness, pain in the upper right part of the abdomen, yellowing or worsening yellow colour of the skin or eyes, and dark-coloured urine (symptoms of liver disease);
• you experience difficulties with thinking, remembering information, or solving problems, become less alert or conscious, or feel drowsy 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");
• you vomit blood and/or pass black stools;
• you frequently have abdominal pain, especially after eating or taking Exferana;
• you frequently have heartburn;
• blood tests show reduced platelet or white blood cell counts;
• you experience blurred vision;
• you have diarrhoea or vomiting.

If any of the above apply to you, inform your doctor immediately.

Monitoring during Exferana treatment
During treatment, you will undergo regular blood and urine tests. These are intended to
monitor the amount of iron in your body (serum ferritin levels) to assess how well 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). Your doctor may order a kidney biopsy if significant kidney damage is suspected. You may also undergo MRI (magnetic resonance imaging) to determine liver iron concentration. Your doctor will use the results of these tests to determine the optimal dose of Exferana for you and to decide when to discontinue treatment.
As a precaution, annual eye and hearing examinations will be performed during treatment.

Exferana with other medicines
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take. These include in particular:

• other iron-chelating agents, which must not be taken with Exferana;
• antacids 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 conditions 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);
• 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 transplantation to destroy existing bone marrow);
• midazolam (used to relieve anxiety and/or sleep problems).

Your 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 doctor for possible adverse reactions, which 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. Your doctor will adjust the dose as the patient grows.
Exferana is not recommended for children under 2 years of age.

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine.
Exferana is not recommended during pregnancy unless there is a clear medical need for treatment.
If you are currently using hormonal contraception to prevent pregnancy, you should use additional or alternative contraception (e.g. condoms), as Exferana may reduce the effectiveness of hormonal contraceptives.
Breastfeeding is not recommended during treatment with Exferana.

Driving and operating machinery
If you experience dizziness while taking Exferana, do not drive or operate machinery until you feel well again.

Exferana contains lactose
If you have been previously diagnosed with intolerance to certain sugars, consult your doctor before taking this medicine.

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

3. How to use Exferana

Treatment with Exferana will be supervised by a physician 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

The dose of Exferana for all patients is based on body weight. Your doctor will calculate the required dose and inform you how many tablets to take each 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 later adjust the dose upward or downward.
• 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 adults not receiving regular blood transfusions,
  • 7 mg per kilogram of body weight in children and adolescents not receiving regular blood transfusions.

In some countries, deferasirox may also be available as tablets for oral suspension produced by other manufacturers. If a patient switches from such tablets for oral suspension to Exferana film-coated tablets, the dose will change. Your treating physician will calculate the required dose and inform you how many film-coated tablets to take daily.

When to take Exferana

• Exferana should be taken once daily, every day, approximately at 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 may help you remember to take your dose.

For patients who cannot swallow tablets whole, Exferana film-coated tablets may be crushed and the entire dose mixed with a soft 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 monitor your health regularly to assess whether the treatment is achieving the desired effects (see also section 2: "Monitoring treatment with Exferana").

If you have any questions about how long treatment with Exferana should continue, please consult your doctor.

Taking more than the recommended dose of Exferana

If you take more than the prescribed dose of Exferana, or if someone else accidentally takes the tablets, seek immediate medical advice from a doctor or go to the nearest hospital. Bring the medicine package with you. Immediate medical treatment may be necessary. Symptoms such as abdominal pain, diarrhea, nausea and vomiting, and kidney or liver problems, which may be serious, may occur.

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 a missed tablet(s).

Stopping Exferana treatment

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

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 in severity and usually resolve within a few days or weeks of treatment.
Some side effects may be serious and require immediate medical attention.
These side effects occur uncommonly (may occur in up to 1 in 100 patients) or rarely (may occur in up to 1 in 1000 patients).

• If the patient develops a severe rash, or has difficulty breathing and dizziness, or swelling, mainly of the face and throat (symptoms of a severe allergic reaction);
• if 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 severe skin reactions);
• if the patient notices a significant decrease in the amount of urine passed (a sign 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 darkening of the urine (symptoms of liver disease);
• if the patient has difficulties with 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 develops sudden severe pain in the upper abdomen (pancreatitis); the medicine should be discontinued and the doctor should be informed immediately.

Some side effects may become serious.
These side effects occur uncommonly.

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

Other side effects
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, indigestion
• 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 passed
• Perforation of the stomach or intestinal wall, which may cause pain and nausea
• Sudden severe pain in the upper abdomen (pancreatitis)
• Abnormal blood acidity

Reporting of side effects
If any side effects occur, including any side effects not listed in this leaflet, the doctor, pharmacist, or nurse should be informed. Side effects 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
Side effects can also be reported to the marketing authorization holder. Reporting side effects helps 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 the 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 180 mg film-coated tablet contains 180 mg of deferasirox.
Each Exferana 360 mg film-coated tablet contains 360 mg of deferasirox.
The other ingredients are:
Tablet core: microcrystalline cellulose (type 101 and 102), povidone K-30, crospovidone (type 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 film-coated tablets. The film-coated tablets are oval and biconvex.
Exferana 180 mg film-coated tablets
Blue, oval, biconvex film-coated tablets approximately 13 mm x 7 mm in size, embossed with "D7FX" on one side and "180" on the other.
Exferana 360 mg film-coated tablets
Dark blue, oval, biconvex film-coated tablets approximately 15 mm x 9 mm in size, embossed with "D7FX" on one side and "360" on the other.
Unit packs containing 30 or 90 film-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 for marketing in the European Economic Area countries under the following names:
Netherlands
Exferana 180 mg filmomhutten tabletten
Exferana 360 mg filmomhutten tabletten
Czech Republic Exferana
Hungary
Exferana 180 mg filmtabletta
Exferana 360 mg filmtabletta
Poland Exferana
Slovakia
Exferana 180 mg
Exferana 360 mg