EXJADE 250 MG

Israel - English - Ministry of Health

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Active ingredient:
DEFERASIROX
Available from:
NOVARTIS ISRAEL LTD
ATC code:
V03AC03
Pharmaceutical form:
TABLETS DISPERSIBLE
Composition:
DEFERASIROX 250 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
NOVARTIS PHARMA STEIN AG, SWITZERLAND
Therapeutic group:
DEFERASIROX
Therapeutic area:
DEFERASIROX
Therapeutic indications:
Exjade is indicated for the treatment of chronic iron overload due to blood transfusions (transfusionalhaemosiderosis) in adult and pediatric patients (aged 2 years and over).Exjade is also indicated for the treatment of chronic iron overload in patients with non-transfusion-dependent thalassemia syndromes aged 10 years and older.Chelation therapy should only be initiated when there is evidence of iron overload (liver iron concentration [LIC] ≥5 mg Fe/g dry weight [dw] or serum ferritin consistently >800 μg/l).LIC is the preferred method of iron overload determination and should be used wherever available
Authorization number:
134 02 31338 00
Authorization date:
2011-01-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

21-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

17-08-2016

PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE

PHARMACISTS’ REGULATIONS (PREPARATIONS) – 1986

The medicine is dispensed with a doctor’s prescription only

EXJADE

®

125 mg

Dispersible tablets

Each dispersible tablet contains:

Deferasirox 125 mg

EXJADE

®

250 mg

Dispersible tablets

Each dispersible tablet contains:

Deferasirox 250 mg

EXJADE

®

500 mg

Dispersible tablets

Each dispersible tablet contains:

Deferasirox 500 mg

Inactive ingredients: See section 6 “Further information”.

Read this package insert carefully in its entirety before using this medicine. This

leaflet contains concise information about the medicine. If you have further questions refer to

the doctor or pharmacist.

This medicine has been prescribed for the treatment of your ailment. Do not pass it on to others.

It may harm them even if it seems to you that their ailment is similar.

1. WHAT IS THIS MEDICINE INTENDED FOR?

∙ Treatment of chronic iron overload caused by blood transfusions, in adults and children (aged

2 years and above).

∙ Treatment of chronic iron overload in patients with non-transfusion-dependent thalassaemia

aged 10 years and older.

Therapeutic group: Iron chelating agent.

Repeated blood transfusions may sometimes be necessary in patients suffering from certain

types of anaemia such as thalassaemia, sickle cell disease and myelodysplastic syndromes.

However, repeated blood transfusions can cause a build-up of excess iron. This is because blood

contains iron and the body does not have a natural way to remove the excess iron received with

the blood transfusions.

In patients with non-transfusion-dependent thalassaemia, iron overload may develop over time,

mainly due to increased absorption of dietary iron in response to low blood cell counts.

Over time, the excess iron can damage important organs such as the liver and heart.

Medicines called iron chelators are used to remove the excess iron and reduce the risk of it

causing organ damage.

Exjade traps and removes excess iron, which is then excreted mainly in the stools.

2. BEFORE USING THE MEDICINE

X

Do not use this medicine if:

∙ you are sensitive (allergic) to deferasirox or any of the other ingredients of the medicine listed

in section 6 “Further information”. If this applies to you, tell your doctor before taking

Exjade. If you think you are allergic, ask your doctor for advice.

∙ you have a moderate or severe kidney disease.

∙ you are currently taking another iron chelator.

Special warnings regarding use of the medicine:

Before taking Exjade, tell the doctor if:

∙ you are at an advanced stage of myelodysplastic syndrome (MDS: decreased production of

blood cells by the bone marrow) or have advanced cancer. Use of Exjade is not recommended

in such cases.

∙ you have a liver or kidney problem.

∙ you have a cardiac problem due to iron overload.

∙ you notice a marked decrease in your urine output (sign of kidney problem).

∙ you develop a severe rash, or difficulty breathing and dizziness or swelling mainly of the face

and throat (signs of severe allergic reaction, see also section 4 “Side effects”).

∙ you develop a rash, reddening of the skin, blistering of lips, eyes or mouth, skin peeling, sore

throat (signs of severe skin reaction, see also section 4 “Side effects”).

∙ you experience a combination of drowsiness, upper right abdominal pain, yellowing or increased

yellowing of your skin or eyes and dark urine (signs of liver problems).

∙ you vomit blood and/or have black stools.

∙ you experience frequent abdominal pain, particularly after eating or taking Exjade.

∙ you experience frequent heartburn.

∙ you have a low level of platelets or white blood cells in your blood tests.

∙ you have blurred vision or vomiting.

∙ you have diarrhoea or vomiting.

If any of these conditions apply to you, tell your doctor straight away.

Elderly people aged 65 and over can use Exjade at the same dose as for other adults. Elderly

patients may experience more side effects (in particular diarrhoea) than younger patients. They

should be monitored closely by their doctor for identification of side effects that may require a

dose adjustment.

Exjade can be used in adolescents and children over the age of 2, for the treatment of chronic

iron overload caused by blood transfusions and over the age of 10 for the treatment of chronic

iron overload in non-transfusion-dependent thalassaemia patients. As the patient grows, the

doctor will adjust the dose.

!

If you are taking, or have recently taken, other medicines, including non-prescription

medicines and nutritional supplements, tell the doctor or pharmacist.

Exjade must not be combined with other iron chelating agents.

Do not take antacids (medicines used to treat heartburn) containing aluminium at the same

time of day as Exjade.

It is particularly important to inform the doctor or pharmacist if you are taking:

∙ ciclosporin (used to prevent the body rejecting a transplanted organ or for other conditions,

such as rheumatoid arthritis or atopic dermatitis)

∙ simvastatin (used to lower cholesterol)

∙ certain painkillers or anti-inflammatory medicines (e.g. aspirin, ibuprofen, corticosteroids)

∙ oral bisphosphonates (used to treat osteoporosis)

∙ anticoagulant medicines (used to prevent or treat blood clotting)

∙ hormonal contraceptive agents (birth control medicines)

∙ bepridil, ergotamine

∙ repaglinide (used to treat diabetes)

∙ rifampicin (used to treat tuberculosis)

∙ phenytoin, phenobarbital, carbamazepine (used to treat epilepsy)

∙ ritonavir (used in the treatment of 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 lower cholesterol levels in the blood)

Additional tests may be required to monitor the blood levels of some of the medicines.

!

Use of Exjade and food

Take Exjade on an empty stomach and wait at least 30 minutes before eating any food, preferably

at the same time each day.

Dissolve the tablets in a glass of water, apple juice or orange juice. Do not dissolve the tablets in

fizzy drinks or milk (also see below “How to take Exjade”).

!

Pregnancy and breast-feeding

Exjade is not recommended during pregnancy unless clearly necessary. If you are pregnant or

think that you may be, tell your doctor who will discuss with you whether you can take Exjade

during your pregnancy.

Breast-feeding is not recommended during treatment with Exjade. Tell your doctor if you are

breast-feeding.

Ask your doctor or pharmacist for advice before taking any medicine.

!

Driving and use of machines

If you feel dizzy after taking Exjade, do not drive a vehicle or operate any tools or machines until

you are feeling normal again.

!

Important information about some of the medicine’s ingredients

Exjade tablets contain lactose (milk sugar). If you have an intolerance to certain sugars, inform

the doctor before taking Exjade.

Each Exjade 125 mg dispersible tablet contains approximately 136 mg lactose monohydrate

and 0.33 mg sodium.

Each Exjade 250 mg dispersible tablet contains approximately 272 mg lactose monohydrate

and 0.67 mg sodium.

Each Exjade 500 mg dispersible tablet contains approximately 544 mg lactose monohydrate

and 1.34 mg sodium.

3. HOW SHOULD YOU USE THE MEDICINE?

Always use according to the doctor’s instructions. Check with the doctor or pharmacist if you

are not sure.

Treatment with Exjade will be overseen by a doctor who is experienced in the treatment of iron

overload caused by blood transfusions.

The usual dosage:

The dosage and the manner of treatment will be determined by the doctor only. The dose of

Exjade is related to 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 daily dose at the start of the treatment is generally:

∙ 20 mg per kilogram body weight for patients receiving regular blood transfusions. A higher or

lower starting dose may be recommended by your doctor based on your individual treatment

needs.

∙ 10 mg per kilogram body weight for patients not receiving regular blood transfusions.

Depending on how you respond to treatment, your doctor may later adjust your treatment to a

higher or lower dose.

The maximum daily dose is:

∙ 40 mg per kilogram body weight for patients receiving regular blood transfusions.

∙ 20 mg per kilogram body weight for adult patients not receiving regular blood transfusions.

∙ 10 mg per kilogram body weight for children not receiving regular blood transfusions.

Do not exceed the recommended dose.

When to take Exjade:

∙ Take Exjade once a day, every day, at about the same time.

∙ Take the tablets on an empty stomach.

∙ Then wait at least 30 minutes before eating any food.

Taking Exjade at the same time each day will help you remember when to take your tablets.

How to take Exjade:

Drop the tablet(s) in a glass of water, apple or orange juice (100-200 ml).

Stir until the tablet(s) dissolve completely. The liquid in the glass will look

cloudy.

Drink the entire contents of the glass. Then add a little water or juice to what

is left in the glass, swirl the liquid around and drink that too.

Do not dissolve the tablets in fizzy drinks or milk.

Do not chew, break or crush the tablets.

Do not swallow the tablets whole.

Duration of treatment:

Continue to take Exjade every day, for as long as the doctor instructs you to do so.

This is a long-term treatment, possibly lasting for months or years. The attending doctor will

regularly monitor your condition to ensure that the treatment is having the desired effect (also

see below: “Tests and follow-up”).

In case you have questions about the duration of the treatment, refer to the attending doctor.

Tests and follow-up:

You will have regular blood and urine tests during treatment. These tests will monitor the amount

of iron in your body (blood ferritin levels) to see how well Exjade is working. The tests will also

monitor your kidney function (blood level of creatinine, presence of protein in the urine) and liver

function (blood transaminase, bilirubin and alkaline phosphatase levels). You may also have MRI

(magnetic resonance imaging) tests to determine the amount of iron in your liver. Your doctor will

take these tests into consideration when deciding on the dose of Exjade most suitable for you and

will also use these tests to decide when you should stop taking Exjade.

You should have hearing and vision tests before initiating treatment and once a year during

treatment as a precautionary measure.

In children, body weight, growth in height and sexual development should be checked once a

year.

If you have any questions about how Exjade works or why this medicine has been prescribed for

you, ask your doctor, pharmacist, or healthcare provider.

If you have taken an overdose, or if a child or someone else has accidentally swallowed the

medicine, proceed immediately to a doctor or a hospital emergency room and bring the package

of the medicine with you. Medical treatment may be necessary.

If you forgot to take this medicine:

If you forgot to take the medicine at the required time, take it as soon as you remember on that

day. Take the next dose at the scheduled time. Do not take a double dose on the next day to

compensate for a forgotten tablet(s).

Adhere to the treatment as recommended by the doctor.

Even if there is an improvement in your health, do not stop treatment with the medicine without

consulting the doctor.

If you stop taking the medicine:

Do not stop treatment with Exjade without explicit instruction from a doctor. If you stop taking

Exjade, the excess iron will no longer be removed from your body (also see above “Duration of

treatment”).

Do not take medicines in the dark! Check the label and the dose each time you take the medicine.

Wear glasses if you need them.

If you have further questions on the use of the medicine, consult the doctor or pharmacist.

4. SIDE EFFECTS

As with any medicine, use of Exjade may cause side effects in some users. Do not be alarmed when

reading the list of side effects. You may not suffer from any of them. Most of the side effects are

mild to moderate and will generally disappear after a few days to a few weeks of treatment.

Some side effects could be serious and need immediate medical attention.

These side effects are uncommon or rare or of unknown frequency.

Stop taking the medicine and refer to a doctor immediately if any of the following

cases apply to you or your child:

∙ severe rash, or difficulty breathing and dizziness or swelling, mainly of the face and throat (signs

of severe allergic reaction)

∙ severe rash, reddening of the skin, blistering of lips, eyes or mouth, skin peeling, sore throat

(signs of severe skin reaction)

∙ marked decrease in your urine output (sign of a kidney problem)

∙ a combination of drowsiness, upper right abdominal pain, yellowing or increased yellowing of

your skin or eyes and dark urine (signs of liver problems)

∙ bloody vomit and/or black stools

∙ frequent abdominal pain, particularly after eating or taking Exjade

∙ frequent heartburn

∙ partial loss of vision

Some side effects could become serious.

These side effects are uncommon, that is, they may affect up to 1 in 100 patients.

Tell your doctor as soon as possible if:

∙ you suffer from blurred or cloudy eyesight

∙ you suffer from reduced hearing

Additional side effects:

If one or more of these side effects affect you severely, inform your doctor.

Very common side effects (may affect more than 1 in every 10 patients):

∙ Abnormal renal function blood tests

Common side effects (may affect up to 1 in every 10 patients):

∙ Gastrointestinal disorders, such as nausea, vomiting, diarrhoea, pain in the abdomen, bloating,

constipation, indigestion

∙ Rash

∙ Headache

∙ Abnormal liver function blood tests

∙ Itching

∙ Abnormal urine tests (protein in the urine)

Uncommon side effects (may affect up to 1 in every 100 patients):

∙ Dizziness

∙ Fever

∙ Sore throat

∙ Swelling of arms or legs

∙ Change in the colour of the skin

∙ Anxiety

∙ Sleep disorder

∙ Tiredness

Side effects with unknown frequency (the frequency can not be estimated from the available

data):

∙ A decrease in the number of blood cells involved in blood clotting (thrombocytopenia), in the

number of red blood cells (anaemia aggravated), in the number of white blood cells (neutropenia)

or in the number of all kinds of blood cells (pancytopenia)

∙ Hair loss

∙ Kidney stones

∙ Low urine output

∙ Formation of a hole in the stomach or intestine

∙ Abnormal level of acid in the blood

If a side effect occurs, if any of the side effects worsen or you suffer from a side effect not mentioned

in this leaflet, talk to your doctor, pharmacist or healthcare provider.

Side effects can be reported to the Ministry of Health by clicking on the “Reporting side effects

following drug treatment” link found on the Ministry of Health homepage (www.health.gov.il) that

directs you to the online form for reporting side effects,

or by entering the link:

https://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@

moh.gov.il

5. HOW SHOULD THE MEDICINE BE STORED?

Avoid poisoning! This medicine and any other medicine must be kept in a closed place out of

the reach of children and/or infants to avoid poisoning. Do not induce vomiting unless explicitly

instructed to do so by the doctor.

Do not use the medicine after the expiry date (exp. date) appearing on the package. The expiry

date refers to the last day of that month.

Do not store above 30°C.

Store in the original package in order to protect from moisture.

Keep out of the reach and sight of children.

Do not use a package that is damaged or shows signs of tampering.

6. FURTHER INFORMATION

In addition to the active ingredient, the medicine also contains:

Crospovidone, lactose monohydrate (200 mesh), lactose monohydrate (spray dried), microcrystalline

cellulose (NF) / cellulose, microcrystalline (Ph. Eur.), povidone (K30), sodium lauryl sulphate,

colloidal silicon dioxide (NF) / silica, colloidal anhydrous (Ph. Eur.), magnesium stearate.

What does the medicine look like and what are the contents of the package:

Exjade is marketed as dispersible tablets in a pack size of 28 tablets.

The Exjade tablets 125 mg, 250 mg and 500 mg are white to yellowish, round and flat, with

beveled edges, stamped with “J125”, “J250” and “J500”, respectively, on one side and “NVR”

on the other side.

Registration Holder and address: Novartis Israel Ltd., 36 Shacham St., Petach-Tikva.

Manufacturer name and address: Novartis Pharma Stein AG, Stein, Switzerland, for Novartis

Pharma AG, Basel, Switzerland.

This leaflet was checked and approved by the Ministry of Health in December 2015.

Registration number of the medicine in the National Drug Registry of the Ministry

of Health:

Exjade 125 mg: 133 99 31337

Exjade 250 mg: 134 02 31338

Exjade 500 mg: 134 01 31339

SH EXJ APL DEC15 CL V8 COR JAN16 CL

SH EXJ APL DEC15 CL V8 COR JAN16 CL

:ﺪﻴﺠﺴﻛﺇ ﻝﻭﺎﻨﺗ ﺔﻴﻔﻴﻛ ﻝﺎﻘﺗﺮﺒﻟﺍ ﺮﻴﺼﻋ ﻭﺃ ﺡﺎﻔﺘﻟﺍ ﺮﻴﺼﻋ ،ﺀﺎﻤﻟﺍ ﻦﻣ ﺱﺄﻛ ﻞــﺧﺍﺩ ﺹﺍﺮﻗﻷﺍ/ﺹﺮﻘﻟﺍ ﻝﺎــﺧﺩﺇ ﺐﺠﻳ .(ﻞﻠﻣ ٢٠٠-١٠٠)

ﺍﺮﻜﻋ ﻭﺪﺒﻳ ﺱﺄﻜﻟﺍ ﻲﻓ ﻞﺋﺎﺴﻟﺍ .ﻡﺎﺗ ﻞﻜﺸﺑ ﺹﺍﺮﻗﻷﺍ/ﺹﺮﻘﻟﺍ ﻥﺎﺑﻭﺫ ﻰﺘﺣ ﻂﻠﺨﻟﺍ ﺐﺠﻳ ﻰﻘﺒﺗ ﺎﻣ ﻰﻠﻋ ﺮﻴﺼﻌﻟﺍ ﻭﺃ ﺀﺎﻤﻟﺍ ﻦﻣ ﻞﻴﻠﻘﻟﺍ ﺔﻓﺎﺿﺇ ﺐﺠﻳ ﻢﺛ ﻦﻣﻭ ،ﺱﺄﻜﻟﺍ ﻯﻮﺘﺤﻣ ﻞﻣﺎﻛ ﺏﺮﺷ ﺐﺠﻳ

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ﺎﻀﻳﺃ ﺹﻮﺤﻔﻟﺍ ﻩﺬﻫ ﺪﻋﺎﺴﺗ .ﻲﻐﺒﻨﻳ ﺎﻤﻛ ﺮﺛﺆﻳ ﺪﻴﺠﺴﻛﺇ ﻥﺎﻛ ﺍﺫﺍ ﺎﻤﻴﻓ ﺪﻛﺄﺘﻠﻟ (ﻡﺪﻟﺍ ﻲﻓ ﻦﻴﺘﻳﺮﻔﻟﺍ ﺯﺎﻨﻴﻣﺄﺴﻧﺍﺮﺗ ﺮﺋﺎﻤﺧ ﺐﺴﻧ) ﻚﻳﺪﻟ ﺪﺒﻜﻟﺍ ﻒﺋﺎﻇﻭﻭ (ﻝﻮﺒﻟﺍ ﻲﻓ ﻦﻴﺗﻭﺮﭙﻟﺍ ﺩﻮﺟﻭ ،ﻡﺪﻟﺍ ﻲﻓ ﻦﻴﻨﻴﺗﺎﻳﺮﻜﻟﺍ ﺐﺴﻧ) ﻚﻳﺪﻟ ﻰﻠﻜﻟﺍ ﻒﺋﺎﻇﻮﻟ ﺪﻳﺪﺤﺘﻟ

(ﻲﺴﻴﻃﺎﻨﻐﻤﻟﺍ ﻦﻴﻧﺮﻟﺎﺑ

ﺮﻳﻮﺼﺘﻟﺍ)

ﺕﺎﺻﻮﺤﻓ ﺯﺎﺘﺠﺗ ﻥﺃ

ﺎﻀﻳﺃ ﺰﺋﺎﺠﻟﺍ ﻦﻣ .(ﺯﺎﺗﺎﻔﺳﻮﻓ ﻦﻳﻻﺎﻜﻟﺃﻭ ﻦﻴﺑﻭﺮﻴﻠﻴﺑ ،ﻡﺪﻟﺍ ﻲﻓ ﺮﺜﻛﺃ ﻚﺒﺳﺎﻨﺗ ﺪﻴﺠﺴﻛﺇ ﻦﻣ ﺔﻴﺋﺍﻭﺩ ﺔﻋﺮﺟ ﻱﺃ ﺭﺮﻘﻳ ﺎﻣﺪﻨﻋ ﺹﻮﺤﻔﻟﺍ ﻩﺬﻫ ﺭﺎﺒﺘﻋﻹﺍ ﻦﻴﻌﺑ ﺬﺧﺄﻳ ﺐﻴﺒﻄﻟﺍ.ﻙﺪﺒﻛ ﻲﻓ ﺪﻳﺪﺤﻟﺍ ﺔﻴﻤﻛ .ﺪﻴﺠﺴﻛﺇ ﻝﻭﺎﻨﺗ ﻦﻋ ﻒﻗﻮﺘﻟﺍ ﻚﻴﻠﻋ ﺐﺟﻮﺘﻳ ﻰﺘﻣ ﺭﺮﻘﻳ ﻲﻛ ﺹﻮﺤﻔﻟﺍ ﻩﺬﻫ ﻞﻤﻌﺘﺴﻳ ﻚﻟﺬﻛ

.ﺭﺬﺣ ﺔﻠﻴﺳﻮﻛ ﺝﻼﻌﻟﺍ ﻝﻼﺧ ﺔﻨﺴﻟﺍ ﻲﻓ ﺓﺮﻣﻭ ﺝﻼﻌﻟﺍ ﺀﺪﺑ ﻞﺒﻗ ﺔﻳﺅﺮﻟﺍﻭ ﻊﻤﺴﻠﻟ ﺹﻮﺤﻓ ﺯﺎﻴﺘﺟﺇ ﻚﻴﻠﻋ ﺐﺟﻮﺘﻳ .ﺔﻨﺴﻟﺍ ﻲﻓ ﺓﺮﻣ ،ﻲﺴﻨﺠﻟﺍ ﻢﻫﺭﻮﻄﺗﻭ ﻥﺯﻮﻟﺍﻭ ﻝﻮﻄﻟﺍ ﺚﻴﺣ ﻦﻣ ﻮﻤﻨﻟﺍ ﺺﺤﻓ ﺐﺠﻳ ﻝﺎﻔﻃﻷﺍ یﺪﻟ ﺍﺫﺎﻤﻟ ﻭﺃ ﺪﻴﺠﺴﻛﺇ ﻞﻤﻋ ﺔﻴﻔﻴﻜﺑ ﻖﻠﻌﺘﻳ ﻝﺍﺆﺳ ﻱﺃ ﺹﻮﺼﺨﺑ ،ﻲﺒﻄﻟﺍ ﻢﻗﺎﻄﻟﺍ ﻦﻣ ﺩﺮﻓ ﻭﺃ ﻲﻟﺪﻴﺼﻟﺍ ،ﺐﻴﺒﻄﻟﺍ ﺔﻌﺟﺍﺮﻣ ﺐﺠﻳ .ﻚﻠﺟﺃ ﻦﻣ ﻒﺻﻭ ﻲﻓ ﺉﺭﺍﻮﻄﻟﺍ ﺔﻓﺮﻐﻟ ﻭﺃ ﺐﻴﺒﻄﻠﻟ

ﻻﺎﺣ ﻪﺟﻮﺗ ،ﺀﺍﻭﺪﻟﺍ ﻦﻣ ﺄﻄﺨﻟﺎﺑ ﺮﺧﺁ ﺺﺨﺷ ﻭﺃ ﻞﻔﻃ ﻊﻠﺑ ﺍﺫﺇ ﻭﺃ ﺔﻃﺮﻔﻣ ﺔﻴﺋﺍﻭﺩ ﺔﻋﺮﺟ ﺖﻟﻭﺎﻨﺗ ﺍﺫﺇ .ﻲﺒﻃ ﺝﻼﻋ ﺮﻣﻷﺍ ﺝﺎﺘﺤﻳ ﻥﺃ ﺰﺋﺎﺠﻟﺍ ﻦﻣ .ﻚﻌﻣ ﺀﺍﻭﺪﻟﺍ ﺔﺒﻠﻋ ﺮﻀﺣﺃﻭ ﻰﻔﺸﺘﺴﻤﻟﺍ :ﺀﺍﻭﺪﻟﺍ ﻝﻭﺎﻨﺗ ﺖﻴﺴﻧ ﺍﺫﺇ ﻲﻓ ﺔﻴﻟﺎﺘﻟﺍ ﺔﻴﺋﺍﻭﺪﻟﺍ ﺔﻋﺮﺠﻟﺍ ﻝﻭﺎﻨﺗ .ﻡﻮﻴﻟﺍ ﺲﻔﻧ ﻲﻓ ﻙﺮﻛﺬﺗ ﺔﻈﺤﻟ ﻚﻟﺬﺑ ﻢﻘﻓ ،ﺏﻮﻠﻄﻤﻟﺍ ﺖﻗﻮﻟﺍ ﻲﻓ ﺀﺍﻭﺪﻟﺍ ﺍﺬﻫ ﻝﻭﺎﻨﺗ ﺖﻴﺴﻧ ﺍﺫﺇ .ﺔﻴﺴﻨﻤﻟﺍ/ﻲﺴﻨﻤﻟﺍ ﺹﺍﺮﻗﻷﺍ/ﺹﺮﻘﻟﺍ ﻦﻋ ﺾﻳﻮﻌﺘﻠﻟ ﻲﻟﺎﺘﻟﺍ ﻡﻮﻴﻟﺍ ﻲﻓ ﺔﻔﻋﺎﻀﻣ ﺔﻴﺋﺍﻭﺩ ﺔﻋﺮﺟ ﻝﻭﺎﻨﺗ ﺯﻮﺠﻳ ﻻ .ﻱﺩﺎﻴﺘﻋﻹﺍ ﺖﻗﻮﻟﺍ .ﺐﻴﺒﻄﻟﺍ ﺔﻴﺻﻮﺗ ﺐﺴﺣ ﺝﻼﻌﻟﺍ ﻰﻠﻋ ﺔﺒﻇﺍﻮﻤﻟﺍ ﺐﺠﻳ .ﻲﺤﺼﻟﺍ ﻚﻌﺿﻭ ﻰﻠﻋ ﻦﺴﺤﺗ ﺃﺮﻃ ﻮﻟﻭ ﻰﺘﺣ ﺐﻴﺒﻄﻟﺍ ﺓﺭﺎﺸﺘﺳﺇ ﻥﻭﺩ ﺀﺍﻭﺪﻟﺎﺑ ﺝﻼﻌﻟﺍ ﻦﻋ ﻒﻗﻮﺘﻟﺍ ﺯﻮﺠﻳ ﻻ :ﺀﺍﻭﺪﻟﺍ ﻝﻭﺎﻨﺗ ﻦﻋ ﺖﻔﻗﻮﺗ ﺍﺫﺇ ﻦﻟ ﺪﻳﺪﺤﻟﺍ ﺾﺋﺎﻓ ﻥﺈﻓ ،ﺪﻴﺠﺴﻛﺇ ﻝﻭﺎﻨﺗ ﻦﻋ ﺖﻔﻗﻮﺗ ﺍﺫﺇ .ﺐﻴﺒﻄﻟﺍ ﻦﻣ ﺔﺤﺿﺍﻭ ﺕﺎﻤﻴﻠﻌﺗ ﻥﻭﺪﺑ ﺪﻴﺠﺴﻛﺇ ـﺑ ﺝﻼﻌﻟﺍ ﻦﻋ ﻒﻗﻮﺘﺗ ﻻ .(«ﺝﻼﻌﻟﺍ ﺓﺮﺘﻓ» ﻩﻼﻋﺃ

ﺎﻀﻳﺃ ﺮﻈﻧﺃ) ﻚﻤﺴﺟ ﻦﻣ ﺔﻴﻧﺎﺛ ﺡﺮﻄﻳ ﺕﺍﺭﺎﻈﻨﻟﺍ ﻊﺿ .ﺀﺍﻭﺩ ﺎﻬﻴﻓ ﻝﻭﺎﻨﺘﺗ ﺓﺮﻣ ﻞﻛ ﻲﻓ ﺔﻴﺋﺍﻭﺪﻟﺍ ﺔﻋﺮﺠﻟﺍ ﻦﻣ ﺪﻛﺄﺘﻟﺍﻭ ﺀﺍﻭﺪﻟﺍ ﻊﺑﺎﻃ ﺺﻴﺨﺸﺗ ﺐﺠﻳ !ﺔﻤﺘﻌﻟﺍ ﻲﻓ ﺔﻳﻭﺩﻷﺍ ﻝﻭﺎﻨﺘﺗ ﻻ .ﻲﻟﺪﻴﺼﻟﺍ ﻭﺃ ﺐﻴﺒﻄﻟﺍ ﺮﺸﺘﺳﺇ ،ﺀﺍﻭﺪﻟﺍ ﻝﺎﻤﻌﺘﺳﺇ ﺹﻮﺼﺨﺑ ﺔﻴﻓﺎﺿﺇ ﺔﻠﺌﺳﺃ ﻚﻳﺪﻟ ﺕﺮﻓﻮﺗ ﺍﺫﺇ .ﻚﻟﺫ ﺮﻣﻷﺍ ﻡﺰﻟ ﺍﺫﺇ ﺔﻴﺒﻄﻟﺍ ﺔﻴﺒﻧﺎﺠﻟﺍ ﺽﺍﺮﻋﻷﺍ (٤ ﺽﺍﺮﻋﻷﺍ ﺔﻤﺋﺎﻗ ﻦﻣ ﺶﻫﺪﻨﺗ ﻻ .ﻦﻴﻠﻤﻌﺘﺴﻤﻟﺍ ﺾﻌﺑ ﺪﻨﻋ ﺔﻴﺒﻧﺎﺟ

ﺎﺿﺍﺮﻋﺃ ﺐﺒﺴﻳ ﺪﻗ ﺪﻴﺠﺴﻛﺇ ﻝﺎﻤﻌﺘﺳﺇ ﻥﺇ ،ﺀﺍﻭﺩ ﻞﻜﺑ ﺎﻤﻛ ﻰﺘﺣ ﻡﺎﻳﺃ ﺓﺪﻋ ﺪﻌﺑ ﻝﻭﺰﺗ ﺓﺩﺎﻋﻭ ﺔﻟﺪﺘﻌﻣ ﻰﺘﺣ ﺔﻄﻴﺴﺑ ﻲﻫ ﺔﻴﺒﻧﺎﺠﻟﺍ ﺽﺍﺮﻋﻷﺍ ﺔﻴﺒﻟﺎﻏ .ﺎﻬﻨﻣ

ﺎﻳﺃ ﻲﻧﺎﻌﺗ ﻻﺃ ﺰﺋﺎﺠﻟﺍ ﻦﻣ .ﺔﻴﺒﻧﺎﺠﻟﺍ .ﺝﻼﻌﻟﺍ ﻦﻣ ﻊﻴﺑﺎﺳﺃ ﺓﺪﻋ .ﻱﺭﻮﻓ ﻲﺒﻃ ﺝﻼﻋ ﺐﻠﻄﺘﺗﻭ ﺔﻳﺪﺟ ﻥﻮﻜﺗ ﻥﺃ ﺎﻬﻧﺄﺷ ﻦﻣ ﺔﻨﻴﻌﻣ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ .ﻑﻭﺮﻌﻣ ﺮﻴﻏ ﺎﻬﻋﻮﻴﺷ ﻭﺃ ﺓﺭﺩﺎﻧ ﻭﺃ ﺔﻌﺋﺎﺷ ﺮﻴﻏ ﻲﻫ ﻩﺬﻫ ﺔﻴﺒﻧﺎﺠﻟﺍ ﺽﺍﺮﻋﻷﺍ :ﺔﻴﻟﺎﺘﻟﺍ ﺕﻻﺎﺤﻟﺍ ﻯﺪﺣﺇ ﻚﻠﻔﻃ ﻰﻠﻋ ﻭﺃ ﻚﻴﻠﻋ ﺖﻘﺒﻄﻧﺇ ﺍﺫﺇ ﺐﻴﺒﻄﻟﺍ ﻰﻟﺇ

ﻻﺎﺣ ﻪﺟﻮﺘﻟﺍﻭ ﺀﺍﻭﺪﻟﺍ ﻝﻭﺎﻨﺗ ﻦﻋ ﻒﻗﻮﺘﻟﺍ ﺐﺠﻳ (ﺪﻳﺪﺷ ﻲﺴﺴﺤﺗ ﻞﻌﻓ ﺩﺮﻟ ﺕﺎﻣﻼﻋ) ﺓﺮﺠﻨﺤﻟﺍﻭ ﻢﻔﻠﻟ ﺔﺻﺎﺧ ﺥﺎﻔﺘﻧﺇ ﻭﺃ ﺭﺍﻭﺩﻭ ﺲﻔﻨﺘﻟﺍ ﻲﻓ ﺕﺎﺑﻮﻌﺻ ﻭﺃ ﺪﻳﺪﺷ ﺢﻔﻃ ﻞﻌﻓ ﺩﺮﻟ ﺕﺎﻣﻼﻋ) ﺓﺮﺠﻨﺤﻟﺍ ﻲﻓ ﻡﻻﺁ ،ﺪﻠﺠﻟﺍ ﺮﺸﻘﺗ ،ﻢﻔﻟﺍ ﻭﺃ ﻦﻴﻨﻴﻌﻟﺍ ،ﻦﻴﺘﻔﺸﻟﺍ ﻲﻓ ﺕﻼﺼﻳﻮﺣ ،ﺪﻠﺠﻟﺍ ﺭﺍﺮﻤﺣﺇ ،ﺪﻳﺪﺷ ﺢﻔﻃ (ﺪﻳﺪﺷ ﻱﺪﻠﺟ (ﻰﻠﻜﻟﺍ ﻲﻓ ﺔﻠﻜﺸﻤﻟ ﺔﻣﻼﻋ) ﻝﻮﺒﺘﻟﺍ ﻲﻓ ﺩﺎﺣ ﺽﺎﻔﺨﻧﺇ

ﻦﻛﺍﺩ ﻝﻮﺑﻭ ﻦﻴﻨﻴﻌﻟﺍ ﻭﺃ ﺪﻠﺠﻟﺍ ﺭﺍﺮﻔﺻﺇ ﺓﺩﺎﻳﺯ ﻭﺃ ﺭﺍﺮﻔﺻﺇ ،ﻦﻄﺒﻟﺍ ﻦﻣ ﻦﻤﻳﻷﺍ ﻱﻮﻠﻌﻟﺍ ﺐﻧﺎﺠﻟﺍ ﻲﻓ ﻢﻟﺃ ،ﺱﺎﻌﻨﻟﺍ ﻦﻣ ﺞﻳﺰﻣ (ﺪﺒﻜﻟﺍ ﻲﻓ ﻞﻛﺎﺸﻤﻟ ﺕﺎﻣﻼﻋ) ﺩﻮﺳﺃ ﺯﺍﺮﺑ ﻭﺃ/ﻭ ﻱﻮﻣﺩ ﺆﻴﻘﺗ ﺪﻴﺠﺴﻛﺇ ﻝﻭﺎﻨﺗ ﻭﺃ ﻡﺎﻌﻄﻟﺍ ﺪﻌﺑ ﺔﺻﺎﺧ ،ﻦﻄﺒﻟﺍ ﻲﻓ ﺓﺭﺮﻜﺘﻣ ﻡﻻﺁ

ﺭﺮﻜﺘﻣ ﻥﺎﻗﺮﺣ ﻲﺋﺰﺟ ﻞﻜﺸﺑ ﺔﻳﺅﺮﻟﺍ ﻥﺍﺪﻘﻓ .ﺔﻳ

ﺪﺟ ﺢﺒﺼﺗ ﻥﺃ ﺎﻬﻧﺄﺷ ﻦﻣ ﺔﻨﻴﻌﻣ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ .ﺞﻟﺎﻌﻣ ١٠٠ ﻞﻛ ﻦﻣ ١ ﺞﻟﺎﻌﻣ ﻰﺘﺣ ﻰﻠﻋ ﺮﺛﺆﺗ ﺪﻗ ﻲﻫ ﻱﺃ ،ﺔﻌﺋﺎﺷ ﺮﻴﻏ ﻲﻫ ﻩﺬﻫ ﺔﻴﺒﻧﺎﺠﻟﺍ ﺽﺍﺮﻋﻷﺍ :ﺍﺫﺇ ﻦﻜﻤﻣ ﺖﻗﻭ ﻉﺮﺳﺄﺑ ﺐﻴﺒﻄﻟﺍ ﺔﻌﺟﺍﺮﻣ ﺐﺠﻳ ﺔﻳﺅﺮﻟﺍ ﻲﻓ ﺔﻴﺑﺎﺒﺿ ﻭﺃ ﺵﻮﺸﺗ ﻦﻣ ﻲﻧﺎﻌﺗ ﺖﻨﻛ ﻊﻤﺴﻟﺍ ﻲﻓ ﻲﻧﺪﺗ ﻦﻣ ﻲﻧﺎﻌﺗ ﺖﻨﻛ :ﺔﻴﻓﺎﺿﺇ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ .ﺐﻴﺒﻄﻟﺍ ﻎ

ﻠﺑ ،ﺪﻳﺪﺷ ﻞﻜﺸﺑ ﺮﺜﻛﺃ ﻭﺃ ﺔﻴﻟﺎﺘﻟﺍ ﺔﻴﺒﻧﺎﺠﻟﺍ ﺽﺍﺮﻋﻷﺍ ﻯﺪﺣﺇ ﻚﻴﻠﻋ ﺕﺮﺛﺃ ﺍﺫﺇ :(ﻦﻴﺠﻟﺎﻌﻣ ١٠ ﻞﻛ ﻲﻓ ﺪﺣﺍﻭ ﺞﻟﺎﻌﻣ ﻦﻣ ﺮﺜﻛﺃ ﻰﻠﻋ ﺮﺛﺆﺗ ﺪﻗ)

ﺍﺪﺟ ﺔﻌﺋﺎﺷ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﺔﻴﻠﻜﻠﻟ ﻲﻔﻴﻇﻮﻟﺍ ﺀﺍﺩﻷﺎﺑ ﺔﻗﻼﻋ ﺕﺍﺫ ﺔﻤﻴﻠﺳ ﺮﻴﻏ ﻡﺩ ﺹﻮﺤﻓ :(ﻦﻴﺠﻟﺎﻌﻣ ١٠ ﻞﻛ ﻲﻓ ﺪﺣﺍﻭ ﺞﻟﺎﻌﻣ ﻰﺘﺣ ﻰﻠﻋ ﺮﺛﺆﺗ ﺪﻗ) ﺔﻌﺋﺎﺷ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﻢﻀﻬﻟﺍ ﻲﻓ ﺕﺎﺑﻮﻌﺻ ،ﻙﺎﺴﻣﺇ ،ﺔﺨﻔﻧ ،ﻦﻄﺒﻟﺍ ﻲﻓ ﻢﻟﺃ ،ﻝﺎﻬﺳﺇ ،ﺆﻴﻘﺗ ،ﻥﺎﻴﺜﻏ ﻞﺜﻣ ﻲﻤﻀﻬﻟﺍ ﺯﺎﻬﺠﻟﺍ ﻲﻓ ﺕﺎﺑﺍﺮﻄﺿﺇ

ﺢﻔﻃ ﻉﺍﺪﺻ ﺪﺒﻜﻠﻟ ﻲﻔﻴﻇﻮﻟﺍ ﺀﺍﺩﻷﺎﺑ ﺔﻗﻼﻋ ﺕﺍﺫ ﺔﻤﻴﻠﺳ ﺮﻴﻏ ﻡﺩ ﺹﻮﺤﻓ ﺔﻜﺣ (ﻝﻮﺒﻟﺍ ﻲﻓ ﻦﻴﺗﻭﺮﭘ) ﺔﻤﻴﻠﺳ ﺮﻴﻏ ﻝﻮﺑ ﺹﻮﺤﻓ :(ﺞﻟﺎﻌﻣ ١٠٠ ﻞﻛ ﻲﻓ ﺪﺣﺍﻭ ﺞﻟﺎﻌﻣ ﻰﺘﺣ ﻰﻠﻋ ﺮﺛﺆﺗ ﻥﺃ ﻦﻜﻤﻳ) ﺔﻌﺋﺎﺷ ﺮﻴﻏ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﺭﺍﻭﺩ ﺔﻧﻮﺨﺳ ﺓﺮﺠﻨﺤﻟﺍ ﻲﻓ ﻢﻟﺃ

ﻦﻴﻠﺟﺮﻟﺍ ﻭﺃ ﻦﻴﻋﺍﺭﺬﻟﺍ ﻲﻓ ﺥﺎﻔﺘﻧﺇ

ﺪﻠﺠﻟﺍ ﻥﻮﻟ ﻲﻓ ﺮﻴﻐﺗ ﻖﻠﻗ ﻡﻮﻨﻟﺍ ﻲﻓ ﺕﺎﺑﺍﺮﻄﺿﺇ

ﻕﺎﻫﺭﺇ

:(ﺓﺮﻓﻮﺘﻤﻟﺍ ﺕﺎﻴﻄﻌﻤﻟﺍ ﻦﻣ ﻉﻮﻴﺸﻟﺍ ﻢﻴﻴﻘﺗ ﻦﻜﻤﻳ ﻻ) ﻑﻭﺮﻌﻣ ﺮﻴﻏ ﻉﻮﻴﺷ ﺕﺍﺫ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﻡﺩ ﺮﻘﻓ) ﺀﺍﺮﻤﺤﻟﺍ ﻡﺪﻟﺍ ﺎﻳﻼﺧ ﺩﺪﻋ ﻲﻓ ،(

thrombocytopenia

) ﻡﺪﻟﺍ ﺮﺜﺨﺗ ﻲﻓ ﻙﺮﺘﺸﺗ ﻲﺘﻟﺍ ﻡﺪﻟﺍ ﺎﻳﻼﺧ ﺩﺪﻋ ﻲﻓ ﺽﺎﻔﺨﻧﺇ

pancytopenia

) ﻡﺪﻟﺍ ﺎﻳﻼﺧ ﻉﺍﻮﻧﺃ ﺔﻓﺎﻛ ﺩﺪﻋ ﻲﻓ ﻭﺃ (

neutropenia

) ﺀﺎﻀﻴﺒﻟﺍ ﻡﺪﻟﺍ ﺎﻳﻼﺧ ﺩﺪﻋ ﻲﻓ ،(ﺪﻳﺪﺷ ﺮﻌﺸﻟﺍ ﻂﻗﺎﺴﺗ ﻰﻠﻜﻟﺍ ﻲﻓ ﻰﺼﺣ ﻝﻮﺒﻠﻟ ﺾﻔﺨﻨﻣ ﺝﺎﺘﻧ ﺀﺎﻌﻣﻷﺍ ﻭﺃ ﺓﺪﻌﻤﻟﺍ ﻲﻓ ﺐﻘﺛ ﻞﻜﺸﺗ ﻡﺪﻟﺍ ﻲﻓ ﺾﻤﺤﻟﺍ ﻦﻣ ﺓﺫﺎﺷ ﺔﺒﺴﻧ ﻚﻴﻠﻋ ،ﺓﺮﺸﻨﻟﺍ ﻩﺬﻫ ﻲﻓ ﺮﻛﺬﻳ ﻢﻟ ﻲﺒﻧﺎﺟ ﺽﺮﻋ ﻦﻣ ﻲﻧﺎﻌﺗ ﺎﻣﺪﻨﻋ ﻭﺃ ،ﺔﻴﺒﻧﺎﺠﻟﺍ ﺽﺍﺮﻋﻷﺍ ﻯﺪﺣﺇ ﺖﻤﻗﺎﻔﺗ ﺍﺫﺇ ،ﻲﺒﻧﺎﺟ ﺽﺮﻋ ﺮﻬﻇ ﺍﺫﺇ .ﻲﺒﻄﻟﺍ ﻢﻗﺎﻄﻟﺍ ﻦﻣ ﺩﺮﻓ ﻭﺃ ﻲﻟﺪﻴﺼﻟﺍ ،ﺐﻴﺒﻄﻟﺍ ﺓﺭﺎﺸﺘﺳﺇ ﺝﻼﻋ ﺐﻘﻋ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﻦﻋ ﻎﻴﻠﺒﺗ» ﻂﺑﺍﺮﻟﺍ ﻰﻠﻋ ﻂﻐﻀﻟﺍ ﺔﻄﺳﺍﻮﺑ ﺔﺤﺼﻟﺍ ﺓﺭﺍﺯﻮﻟ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﻦﻋ ﻎﻴﻠﺒﺘﻟﺍ ﻥﺎﻜﻣﻹﺎﺑ ﺮﺷﺎﺒﻤﻟﺍ ﺝﺫﻮﻤﻨﻠﻟ ﻚﻬﺟﻮﻳ ﻱﺬﻟﺍ (

www.health.gov.il

) ﺔﺤﺼﻟﺍ ﺓﺭﺍﺯﻭ ﻊﻗﻮﻤﻟ ﺔﻴﺴﻴﺋﺮﻟﺍ ﺔﺤﻔﺼﻟﺍ ﻰﻠﻋ ﺩﻮﺟﻮﻤﻟﺍ «ﻲﺋﺍﻭﺩ ،ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﻦﻋ ﻎﻴﻠﺒﺘﻠﻟ :ﻂﺑﺍﺮﻟﺍ ﺢﻔﺼﺗ ﻖﻳﺮﻃ ﻦﻋ ﻭﺃ ؟ﺀﺍﻭﺪﻟﺍ ﻦﻳﺰﺨﺗ ﺔﻴﻔﻴﻛ(٥ ﻚﻟﺫﻭ ،ﻊﺿﺮﻟﺍ ﻭﺃ/ﻭ ﻝﺎﻔﻃﻷﺍ ﻱﺪﻳﺃ ﻝﻭﺎﻨﺘﻣ ﻦﻋ

ﺍﺪﻴﻌﺑ ﻖﻠﻐﻣ ﻥﺎﻜﻣ ﻲﻓ ﺮﺧﺁ ﺀﺍﻭﺩ ﻞﻛﻭ ﺀﺍﻭﺪﻟﺍ ﺍﺬﻫ ﻆﻔﺣ ﺐﺠﻳ !ﻢﻤﺴﺘﻟﺍ ﺐﻨﺠﺗ .ﺐﻴﺒﻄﻟﺍ ﻦﻣ ﺔﺤﻳﺮﺻ ﺕﺎﻤﻴﻠﻌﺗ ﻥﻭﺪﺑ ﺆﻴﻘﺘﻟﺍ ﺐﺒﺴﺗ ﻻ .ﻢﻤﺴﺘﻟﺎﺑ ﻢﻬﺘﺑﺎﺻﺇ ﻱﺩﺎﻔﺘﻟ ﺔﻴﺣﻼﺼﻟﺍ ﺦﻳﺭﺎﺗ ﺮﻴﺸﻳ .ﺔﺒﻠﻌﻟﺍ ﺮﻬﻇ ﻰﻠﻋ ﺮﻬﻈﻳ ﻱﺬﻟﺍ (

date

) ﺔﻴﺣﻼﺼﻟﺍ ﺦﻳﺭﺎﺗ ﺀﺎﻀﻘﻧﺇ ﺪﻌﺑ ﺀﺍﻭﺪﻟﺍ ﻝﺎﻤﻌﺘﺳﺇ ﺯﻮﺠﻳ ﻻ .ﺮﻬﺸﻟﺍ ﺲﻔﻧ ﻦﻣ ﺮﻴﺧﻷﺍ ﻡﻮﻴﻟﺍ ﻰﻟﺇ .ﺔﻳﻮﺌﻣ ﺔﺟﺭﺩ ٣٠ ﻦﻋ ﺪﻳﺰﺗ ﺓﺭﺍﺮﺣ ﺔﺟﺭﺪﺑ ﻦﻳﺰﺨﺘﻟﺍ ﺯﻮﺠﻳ ﻻ .ﺔﺑﻮﻃﺮﻟﺍ ﻦﻣ ﺔﻳﺎﻤﺤﻠﻟ ﺔﻴﻠﺻﻷﺍ ﺔﺒﻠﻌﻟﺍ ﻲﻓ ﻦﻳﺰﺨﺘﻟﺍ ﺐﺠﻳ .ﻢﻬﺘﻳﺅﺭ ﻝﺎﺠﻣ ﻦﻋﻭ ﻝﺎﻔﻃﻷﺍ ﻱﺪﻳﺃ ﻝﻭﺎﻨﺘﻣ ﻦﻋ ﺀﺍﻭﺪﻟﺍ ﺩﺎﻌﺑﺇ ﺐﺠﻳ .ﺐﻄﻋ ﺩﻮﺟﻭ ﻰﻠﻋ ﻝﺪﺗ ﺕﺎﻣﻼﻋ ﺕﺍﺫ ﻭﺃ ،ﺔﺑﻮﻄﻌﻣ ﺔﺒﻠﻋ ﻝﺎﻤﻌﺘﺳﺇ ﺯﻮﺠﻳ ﻻ ﺔﻴﻓﺎﺿﺇ ﺕﺎﻣﻮﻠﻌﻣ (٦

ﺎﻀﻳﺃ ﺔﻟﺎﻌﻔﻟﺍ ﺓﺩﺎﻤﻠﻟ ﺔﻓﺎﺿﻹﺎﺑ ﺀﺍﻭﺪﻟﺍ ﻱﻮﺘﺤﻳ :ﺔﺒﻠﻌﻟﺍ ﻯﻮﺘﺤﻣ ﺎﻣﻭ ﺀﺍﻭﺪﻟﺍ ﻭﺪﺒﻳ ﻒﻴﻛ

ﺎﺻﺮﻗ ٢٨ ﺕﺍﺫ ﺔﺒﻠﻋ ﻢﺠﺤﺑ ﺔﺑﺍﻭﺫ ﺹﺍﺮﻗﺃ ﻞﻜﺷ ﻰﻠﻋ ﻕ

ﻮﺴﻣ ﺪﻴﺠﺴﻛﺇ ﻊﻣ ﺔﻠﺋﺎﻣ ﻑﺍﺮﻃﺃ ﻊﻣ ﺔﺤﻄﺴﻣﻭ ﺓﺮﻳﺪﺘﺴﻣ ،ﺮﻔﺻﻸﻟ ﻞﺋﺎﻣ ﺾﻴﺑﺃ ﻥﻮﻠﺑ ﻲﻫ ﻎﻠﻣ ٥٠٠ ـ ﻭ ﻎﻠﻣ ٢٥٠ ،ﻎﻠﻣ ١٢٥ ﺪﻴﺠﺴﻛﺇ ﺹﺍﺮﻗﺃ .ﺮﺧﻵﺍ ﺐﻧﺎﺠﻟﺍ ﻲﻓ «

» ـﻭ ﺪﺣﺍﻭ ﺐﻧﺎﺟ ﻲﻓ ﻞﺴﻠﺴﺘﻟﺍ ﺐﺴﺣ ،«

J500

»-ﻭ «

J250

» ،«

J125

» ﺔﻌﺒﻄﻟﺍ .ﺎﭭﻜﺗ ـ ﺢﺘﻴﭘ ،٣٦ ﻡﺎﺣﺎﺷ ﻉﺭﺎﺷ ،.ﺽ.ﻡ ﻞﻴﺋﺍﺮﺳﺇ ﺲﻴﺗﺭﺎﭬﻮﻧ :ﻪﻧﺍﻮﻨﻋﻭ ﺯﺎﻴﺘﻣﻹﺍ ﺐﺣﺎﺻ ،ﻝﺯﺎﺑ ،ﻲﺟ ﻲﻳﺍ ﺎﻣﺭﺎﻓ ﺲﻴﺗﺭﺎﭬﻮﻧ ﻞﺟﺃ ﻦﻣ ﺍﺮﺴﻳﻮﺳ ،ﻦﻳﺎﻄﺷ ،ﻲﺟ ﻲﻳﺍ ﻦﻳﺎﻄﺷ ﺎﻣﺭﺎﻓ ﺲﻴﺗﺭﺎﭬﻮﻧ :ﻪﻧﺍﻮﻨﻋﻭ ﺞﺘﻨﻤﻟﺍ ﻢﺳﺇ .ﺍﺮﺴﻳﻮﺳ ٢٠١٥ ﻝﻭﻷﺍ ﻥﻮﻧﺎﻛ :ﺦﻳﺭﺎﺗ ﻲﻓ ﺺﺧﺭﻭ ﺺﺤﻓ ﺎﻫﺍﻮﺘﺤﻣﻭ ﺓﺮﺸﻨﻟﺍ ﻩﺬﻫ ﺔﻐﻴﺻ ﺔﺤﺼﻟﺍ ﺓﺭﺍﺯﻭ ﺕﺮﻗﺃ :ﺔﺤﺼﻟﺍ ﺓﺭﺍﺯﻭ ﻲﻓ ﻲﻣﻮﻜﺤﻟﺍ ﺔﻳﻭﺩﻷﺍ ﻞﺠﺳ ﻲﻓ ﺀﺍﻭﺪﻟﺍ ﻞﺠﺳ ﻢﻗﺭ ١٣٣ ٩٩ ٣١٣٣٧ :ﻎﻠﻣ ١٢٥ ﺪﻴﺠﺴﻛﺇ ١٣٤ ٠٢ ٣١٣٣٨ :ﻎﻠﻣ ٢٥٠ ﺪﻴﺠﺴﻛﺇ ١٣٤ ٠١ ٣١٣٣٩ :ﻎﻠﻣ ٥٠٠ ﺪﻴﺠﺴﻛﺇ ﻼﻜﻟ ﺺﺼﺨﻣ ﺀﺍﻭﺪﻟﺍ ﻥﺈﻓ ،ﻚﻟﺫ ﻦﻣ ﻢﻏﺮﻟﺍ ﻰﻠﻋ . ﺮﻛﺬﻤﻟﺍ ﺔﻐﻴﺼﺑ ﺓﺮﺸﻨﻟﺍ ﻩﺬﻫ ﺔﻏﺎﻴﺻ ﺖﻤﺗ ،ﺓﺀﺍﺮﻘﻟﺍ ﻞﻴﻬﺴﺗﻭ ﻦﻳﻮﻬﺗ ﻞﺟﺃ ﻦﻣ .ﻦﻴﺴﻨﺠﻟﺍ

Crospovidone, lactose monohydrate (200 mesh), lactose monohydrate (spray dried),

microcrystalline cellulose (NF) / cellulose, microcrystalline (Ph. Eur.), povidone (K30), sodium

lauryl sulphate, colloidal silicon dioxide (NF) / silica, colloidal anhydrous (Ph. Eur.), magnesium

stearate.

https://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@

moh.gov.il

EXJ API DEC15 CL V11 COR DEC15 CL

REF SmPC APR15

This leaflet format has been determined by the Ministry of Health and the content thereof has

been checked and approved in December 2015.

1.

NAME OF THE MEDICINAL PRODUCT

EXJADE 125 mg, 250 mg, 500 mg

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Exjade 125mg: Each dispersible tablet contains 125 mg deferasirox.

Exjade 250mg: Each dispersible tablet contains 250 mg deferasirox.

Exjade 500mg: Each dispersible tablet contains 500 mg deferasirox.

Excipient:

Exjade 125mg: Each dispersible tablet contains about 136 mg lactose monohydrate and 0.33mg

sodium.

Exjade 250mg: Each dispersible tablet contains about 272 mg lactose monohydrate and 0.67mg

sodium.

Exjade 500mg: Each dispersible tablet contains about 544 mg lactose monohydrate and 1.34mg

sodium.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Dispersible tablet

Exjade 125mg: White to slightly yellow, round, flat tablets with bevelled edges and imprints (NVR on

one face and J 125 on the other).

Exjade 250mg: White to slightly yellow, round, flat tablets with bevelled edges and imprints (NVR on

one face and J 250 on the other).

Exjade 500mg: White to slightly yellow, round, flat tablets with bevelled edges and imprints (NVR on

one face and J 500 on the other).

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

EXJADE is indicated for the treatment of chronic iron overload due to blood transfusions

(transfusional haemosiderosis) in adult and paediatric patients (aged 2 years and over).

EXJADE is also indicated for the treatment of chronic iron overload in patients with non-transfusion-

dependent thalassaemia syndromes aged 10 years and older.

Chelation therapy should only be initiated when there is evidence of iron overload (liver iron

concentration [LIC] ≥5 mg Fe/g dry weight [dw] or serum ferritin consistently >800 μg/l). LIC is the

preferred method of iron overload determination and should be used wherever available.

4.2

Posology and method of administration

Treatment with EXJADE should be initiated and maintained by physicians experienced in the

treatment of chronic iron overload.

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REF SmPC APR15

Posology - transfusional iron overload

It is recommended that treatment be started after the transfusion of approximately 20 units (about

100 ml/kg) of packed red blood cells or when there is evidence from clinical monitoring that chronic

iron overload is present (e.g. serum ferritin >1,000 µg/l). Doses (in mg/kg) must be calculated and

rounded to the nearest whole tablet size.

The goals of iron chelation therapy are to remove the amount of iron administered in transfusions and,

as required, to reduce the existing iron burden.

Starting dose

The recommended initial daily dose of EXJADE is 20 mg/kg body weight.

An initial daily dose of 30 mg/kg may be considered for patients who require reduction of elevated

body iron levels and who are also receiving more than 14 ml/kg/month of packed red blood cells

(approximately >4 units/month for an adult).

An initial daily dose of 10 mg/kg may be considered for patients who do not require reduction of body

iron levels and who are also receiving less than 7 ml/kg/month of packed red blood cells

(approximately <2 units/month for an adult). The patient’s response must be monitored and a dose

increase should be considered if sufficient efficacy is not obtained (see section 5.1).

For patients already well managed on treatment with deferoxamine, a starting dose of EXJADE that is

numerically half that of the deferoxamine dose could be considered (e.g. a patient receiving

40 mg/kg/day of deferoxamine for 5 days per week (or equivalent) could be transferred to a starting

daily dose of 20 mg/kg/day of EXJADE). When this results in a daily dose less than 20 mg/kg body

weight, the patient’s response must be monitored and a dose increase should be considered if

sufficient efficacy is not obtained (see section 5.1).

Dose adjustment

It is recommended that serum ferritin be monitored every month and that the dose of EXJADE be

adjusted, if necessary, every 3 to 6 months based on the trends in serum ferritin. Dose adjustments

may be made in steps of 5 to 10 mg/kg and are to be tailored to the individual patient’s response and

therapeutic goals (maintenance or reduction of iron burden). In patients not adequately controlled

with doses of 30 mg/kg (e.g. serum ferritin levels persistently above 2,500 µg/l and not showing a

decreasing trend over time), doses of up to 40 mg/kg may be considered. The availability of long-term

efficacy and safety data with EXJADE used at doses above 30 mg/kg is currently limited (264 patients

followed for an average of 1 year after dose escalation). If only very poor haemosiderosis control is

achieved at doses up to 30 mg/kg, a further increase (to a maximum of 40 mg/kg) may not achieve

satisfactory control, and alternative treatment options may be considered. If no satisfactory control is

achieved at doses above 30 mg/kg, treatment at such doses should not be maintained and alternative

treatment options should be considered whenever possible. Doses above 40 mg/kg are not

recommended because there is only limited experience with doses above this level.

In patients treated with doses greater than 30 mg/kg, dose reductions in steps of 5 to 10 mg/kg should

be considered when control has been achieved (e.g. serum ferritin levels persistently below 2,500 µg/l

and showing a decreasing trend over time). In patients whose serum ferritin level has reached the

target (usually between 500 and 1,000 µg/l), dose reductions in steps of 5 to 10 mg/kg should be

considered to maintain serum ferritin levels within the target range. If serum ferritin falls consistently

below 500 µg/l, an interruption of treatment should be considered (see section 4.4).

Posology - non-transfusion-dependent thalassaemia syndromes

Chelation therapy should only be initiated when there is evidence of iron overload (liver iron

concentration [LIC] ≥5 mg Fe/g dry weight [dw] or serum ferritin consistently >800 µg/l). LIC is the

preferred method of iron overload determination and should be used wherever available. Caution

should be taken during chelation therapy to minimise the risk of over-chelation in all patients.

EXJ API DEC15 CL V11 COR DEC15 CL

REF SmPC APR15

Starting dose

The recommended initial daily dose of EXJADE in patients with non-transfusion-dependent

thalassaemia syndromes is 10 mg/kg body weight.

Dose adjustment

It is recommended that serum ferritin be monitored every month. After every 3 to 6 months of

treatment, a dose increase in increments of 5 to 10 mg/kg should be considered if the patient’s LIC is

≥7 mg Fe/g dw, or if serum ferritin is consistently >2,000 µg/l and not showing a downward trend,

and the patient is tolerating the medicinal product well. Doses above 20 mg/kg are not recommended

because there is no experience with doses above this level in patients with non-transfusion-dependent

thalassaemia syndromes.

In patients in whom LIC was not assessed and serum ferritin is ≤2,000 µg/l, dosing should not exceed

10 mg/kg.

For patients in whom the dose was increased to >10 mg/kg, dose reduction to 10 mg/kg or less is

recommended when LIC is <7 mg Fe/g dw or serum ferritin is ≤2,000 µg/l.

Treatment cessation

Once a satisfactory body iron level has been achieved (LIC <3 mg Fe/g dw or serum ferritin

<300 µg/l), treatment should be stopped. There are no data available on the retreatment of patients

who reaccumulate iron after having achieved a satisfactory body iron level and therefore retreatment

cannot be recommended.

Special populations

Elderly patients (≥65 years of age)

The dosing recommendations for elderly patients are the same as described above. In clinical trials,

elderly patients experienced a higher frequency of adverse reactions than younger patients (in

particular, diarrhoea) and should be monitored closely for adverse reactions that may require a dose

adjustment.

Paediatric population

The dosing recommendations for paediatric patients aged 2 to 17 years with transfusional iron

overload are the same as for adult patients. Changes in weight of paediatric patients over time must be

taken into account when calculating the dose.

In children with transfusional iron overload aged between 2 and 5 years, exposure is lower than in

adults (see section 5.2). This age group may therefore require higher doses than are necessary in

adults. However, the initial dose should be the same as in adults, followed by individual titration.

In paediatric patients with non-transfusion-dependent thalassaemia syndromes, dosing should not

exceed 10 mg/kg. In these patients, closer monitoring of LIC and serum ferritin is essential to avoid

overchelation: in addition to monthly serum ferritin assessments, LIC should be monitored every three

months when serum ferritin is ≤800 µg/l.

The safety and efficacy of EXJADE in children from birth to 23 months of age have not been

established. No data are available.

Patients with renal impairment

EXJADE has not been studied in patients with renal impairment and is contraindicated in patients

with estimated creatinine clearance <60 ml/min (see sections 4.3 and 4.4).

Patients with hepatic impairment

EXJADE is not recommended in patients with severe hepatic impairment (Child-Pugh Class C). In

patients with moderate hepatic impairment (Child-Pugh Class B), the dose should be considerably

EXJ API DEC15 CL V11 COR DEC15 CL

REF SmPC APR15

reduced followed by progressive increase up to a limit of 50% (see sections 4.4 and 5.2), and

EXJADE must be used with caution in such patients. Hepatic function in all patients should be

monitored before treatment, every 2 weeks during the first month and then every month (see section

4.4).

Method of administration

For oral use.

EXJADE must be taken once daily on an empty stomach at least 30 minutes before food, preferably at

the same time each day (see sections 4.5 and 5.2).

The tablets are dispersed by stirring in a glass of water or orange or apple juice (100 to 200 ml) until a

fine suspension is obtained. After the suspension has been swallowed, any residue must be

resuspended in a small volume of water or juice and swallowed. The tablets must not be chewed or

swallowed whole (see also section 6.2).

4.3

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Combination with other iron chelator therapies as the safety of such combinations has not been

established (see section 4.5).

Patients with estimated creatinine clearance <60 ml/min.

4.4

Special warnings and precautions for use

Renal function:

EXJADE has been studied only in patients with baseline serum creatinine within the age-appropriate

normal range.

During clinical trials, increases in serum creatinine of >33% on ≥2 consecutive occasions, sometimes

above the upper limit of the normal range, occurred in about 36% of patients. These were dose-

dependent. About two-thirds of the patients showing serum creatinine increase returned below the

33% level without dose adjustment. In the remaining third the serum creatinine increase did not

always respond to a dose reduction or a dose interruption. Cases of acute renal failure have been

reported following post-marketing use of EXJADE (see section 4.8). In some post-marketing cases,

renal function deterioration has led to renal failure requiring temporary or permanent dialysis.

The causes of the rises in serum creatinine have not been elucidated. Particular attention should

therefore be paid to monitoring of serum creatinine in patients who are concomitantly receiving

medicinal products that depress renal function, and in patients who are receiving high doses of

EXJADE and/or low rates of transfusion (<7 ml/kg/month of packed red blood cells or

<2 units/month for an adult). While no increase in renal adverse events was observed after dose

escalation to doses above 30 mg/kg in clinical trials, an increased risk of renal adverse events with

EXJADE doses above 30 mg/kg cannot be excluded.

It is recommended that serum creatinine be assessed in duplicate before initiating therapy. Serum

creatinine, creatinine clearance (estimated with the Cockcroft-Gault or MDRD formula in adults

and with the Schwartz formula in children) and/or plasma cystatin C levels should be monitored

weekly in the first month after initiation or modification of therapy with EXJADE, and monthly

thereafter. Patients with pre-existing renal conditions and patients who are receiving medicinal

products that depress renal function may be more at risk of complications. Care should be taken to

maintain adequate hydration in patients who develop diarrhoea or vomiting.

There have been post-marketing reports of metabolic acidosis occurring during treatment with

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EXJADE. The majority of these patients had renal impairment, renal tubulopathy (Fanconi’s

syndrome) or diarrhoea, or conditions where acid-base imbalance is a known complication. Acid-base

balance should be monitored as clinically indicated in these populations. Interruption of EXJADE

therapy should be considered in patients who develop metabolic acidosis.

For adult patients, the daily dose may be reduced by 10 mg/kg if a rise in serum creatinine by >33%

above the average of the pre-treatment measurements and estimated creatinine clearance decreases

below the lower limit of the normal range (<90 ml/min) are seen at two consecutive visits, and cannot

be attributed to other causes (see section 4.2). For paediatric patients, the dose may be reduced by

10 mg/kg if estimated creatinine clearance decreases below the lower limit of the normal range

(<90 ml/min) and/or serum creatinine levels rise above the age-appropriate upper limit of normal at

two consecutive visits.

After a dose reduction, for adult and paediatric patients, treatment should be interrupted if a rise in

serum creatinine >33% above the average of the pre-treatment measurements is observed and/or the

calculated creatinine clearance falls below the lower limit of the normal range. Treatment may be

reinitiated depending on the individual clinical circumstances.

Tests for proteinuria should be performed monthly. As needed, additional markers of renal tubular

function (e.g. glycosuria in non-diabetics and low levels of serum potassium, phosphate, magnesium

or urate, phosphaturia, aminoaciduria) may also be monitored. Dose reduction or interruption may be

considered if there are abnormalities in levels of tubular markers and/or if clinically indicated. Renal

tubulopathy has been mainly reported in children and adolescents with beta-thalassaemia treated with

EXJADE.

If, despite dose reduction and interruption, the serum creatinine remains significantly elevated and

there is also persistent abnormality in another marker of renal function (e.g. proteinuria, Fanconi’s

Syndrome), the patient should be referred to a renal specialist, and further specialised investigations

(such as renal biopsy) may be considered.

Hepatic function:

Liver function test elevations have been observed in patients treated with EXJADE. Post-marketing

cases of hepatic failure, sometimes fatal, have been reported in patients treated with EXJADE. Most

reports of hepatic failure involved patients with significant morbidities including pre-existing liver

cirrhosis. However, the role of EXJADE as a contributing or aggravating factor cannot be excluded

(see section 4.8).

It is recommended that serum transaminases, bilirubin and alkaline phosphatase be checked before the

initiation of treatment, every 2 weeks during the first month and monthly thereafter. If there is a

persistent and progressive increase in serum transaminase levels that cannot be attributed to other

causes, EXJADE should be interrupted. Once the cause of the liver function test abnormalities has

been clarified or after return to normal levels, cautious re-initiation of treatment at a lower dose

followed by gradual dose escalation may be considered.

EXJADE is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) (see

section 5.2).

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Summary of safety monitoring recommendations:

In patients with a short life expectancy (e.g. high-risk myelodysplastic syndromes), especially when

co-morbidities could increase the risk of adverse events, the benefit of EXJADE might be limited and

may be inferior to risks. As a consequence, treatment with EXJADE is not recommended in these

patients.

Caution should be used in elderly patients due to a higher frequency of adverse reactions (in

particular, diarrhoea).

Data in children with non-transfusion-dependent thalassaemia are very limited (see section 5.1). As a

consequence, EXJADE therapy should be closely monitored to detect side effects and to follow iron

burden in the paediatric population. In addition, before treating heavily iron-overloaded children with

non-transfusion-dependent thalassaemia with EXJADE, the physician should be aware that the

consequences of long-term exposure in such patients are currently not known.

Gastrointestinal

Upper gastrointestinal ulceration and haemorrhage have been reported in patients, including children

and adolescents, receiving EXJADE. Multiple ulcers have been observed in some patients (see section

4.8). There have been reports of ulcers complicated with digestive perforation. Also, there have been

reports of fatal gastrointestinal haemorrhages, especially in elderly patients who had haematological

malignancies and/or low platelet counts. Physicians and patients should remain alert for signs and

symptoms of gastrointestinal ulceration and haemorrhage during EXJADE therapy and promptly

initiate additional evaluation and treatment if a serious gastrointestinal adverse reaction is suspected.

Caution should be exercised in patients who are taking EXJADE in combination with substances that

have known ulcerogenic potential, such as NSAIDs, corticosteroids, or oral bisphosphonates, in

patients receiving anticoagulants and in patients with platelet counts below 50,000/mm

(50 x 10

(see section 4.5).

Skin disorders

Skin rashes may appear during EXJADE treatment. The rashes resolve spontaneously in most cases.

When interruption of treatment may be necessary, treatment may be reintroduced after resolution of

the rash, at a lower dose followed by gradual dose escalation. In severe cases this reintroduction could

Test

Frequency

Serum creatinine, creatinine clearance

and/or plasma cystatin C

In duplicate prior to therapy.

Weekly during first month of therapy and

during first month after dose modification.

Monthly thereafter.

Proteinuria

Monthly

Other markers of renal tubular function

(such as glycosuria in non-diabetics and

low levels of serum potassium,

phosphate, magnesium or urate,

phosphaturia, aminoaciduria)

As needed.

Serum transaminases, bilirubin, alkaline

phosphatase

Prior to therapy.

Every 2 weeks during first month of

therapy.

Monthly thereafter.

Auditory and ophthalmic testing

Prior to therapy.

Annually thereafter.

Body weight, height and sexual

development

Annually in paediatric patients.

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be conducted in combination with a short period of oral steroid administration. Cases of Stevens-

Johnson syndrome (SJS) have been reported post marketing. The risk of other more severe skin

reactions (TEN [toxic epidermal necrolysis], DRESS [drug reaction with eosinophilia and systemic

symptoms]) cannot be excluded. If SJS

or any other severe skin reaction is suspected, EXJADE

should be discontinued immediately and should not be reintroduced.

Hypersensitivity reactions

Cases of serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported

in patients receiving EXJADE, with the onset of the reaction occurring in the majority of cases within

the first month of treatment (see section 4.8). If such reactions occur, EXJADE should be

discontinued and appropriate medical intervention instituted. Deferasirox should not be reintroduced

in patients who have experienced a hypersensitivity reaction due to the risk of anaphylactic shock (see

section 4.3).

Vision and hearing

Auditory (decreased hearing) and ocular (lens opacities) disturbances have been reported (see section

4.8). Auditory and ophthalmic testing (including fundoscopy) is recommended before the start of

treatment and at regular intervals thereafter (every 12 months). If disturbances are noted during the

treatment, dose reduction or interruption may be considered.

Blood disorders

There have been post-marketing reports of leukopenia, thrombocytopenia or pancytopenia (or

aggravation of these cytopenias) and of aggravated anaemia in patients treated with EXJADE. Most of

these patients had pre-existing haematological disorders that are frequently associated with bone

marrow failure. However, a contributory or aggravating role cannot be excluded. Interruption of

treatment should be considered in patients who develop unexplained cytopenia.

Other considerations

Monthly monitoring of serum ferritin is recommended in order to assess the patient’s response to

therapy (see section 4.2). If serum ferritin falls consistently below 500 µg/l (in transfusional iron

overload) or below 300 µg/l (in non-transfusion-dependent thalassaemia syndromes), an interruption

of treatment should be considered.

The results of the tests for serum creatinine, serum ferritin and serum transaminases should be

recorded and regularly assessed for trends. The results should also be noted in the provided patient’s

booklet.

In one clinical study, growth and sexual development of paediatric patients treated with EXJADE for

up to 5 years were not affected. However, as a general precautionary measure in the management of

paediatric patients with transfusional iron overload, body weight, height and sexual development

should be monitored at regular intervals (every 12 months).

Cardiac dysfunction is a known complication of severe iron overload. Cardiac function should be

monitored in patients with severe iron overload during long-term treatment with EXJADE.

The tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp

lactase deficiency, glucose-galactose malabsorption or severe lactase deficiency should not take this

medicine.

4.5

Interaction with other medicinal products and other forms of interaction

The safety of EXJADE in combination with other iron chelators has not been established. Therefore,

it must not be combined with other iron chelator therapies (see section 4.3).

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The concomitant administration of EXJADE with substances that have known ulcerogenic potential,

such as NSAIDs (including acetylsalicylic acid at high dosage), corticosteroids or oral

bisphosphonates may increase the risk of gastrointestinal toxicity (see section 4.4). The concomitant

administration of EXJADE with anticoagulants may also increase the risk of gastrointestinal

haemorrhage. Close clinical monitoring is required when deferasirox is combined with these

substances.

The bioavailability of deferasirox was increased to a variable extent when taken along with food.

EXJADE must therefore be taken on an empty stomach at least 30 minutes before food, preferably at

the same time each day (see sections 4.2 and 5.2).

Deferasirox metabolism depends on UGT enzymes. In a healthy volunteer study, the concomitant

administration of EXJADE (single dose of 30 mg/kg) and the potent UGT inducer, rifampicin,

(repeated dose of 600 mg/day) resulted in a decrease of deferasirox exposure by 44% (90% CI: 37% -

51%). Therefore, the concomitant use of EXJADE with potent UGT inducers (e.g. rifampicin,

carbamazepine, phenytoin, phenobarbital, ritonavir) may result in a decrease in EXJADE efficacy.

The patient’s serum ferritin should be monitored during and after the combination, and the dose of

EXJADE adjusted if necessary.

Cholestyramine significantly reduced the deferasirox exposure in a mechanistic study to determine the

degree of enterohepatic recycling (see section 5.2).

In a healthy volunteer study, the concomitant administration of EXJADE and midazolam (a CYP3A4

probe substrate) resulted in a decrease of midazolam exposure by 17% (90% CI: 8% - 26%). In the

clinical setting, this effect may be more pronounced. Therefore, due to a possible decrease in efficacy,

caution should be exercised when deferasirox is combined with substances metabolised through

CYP3A4 (e.g. ciclosporin, simvastatin, hormonal contraceptive agents, bepridil, ergotamine).

In a healthy volunteer study, the concomitant administration of deferasirox as a moderate CYP2C8

inhibitor (30 mg/kg daily), with repaglinide, a CYP2C8 substrate, given as a single dose of 0.5 mg,

increased repaglinide AUC and C

about 2.3-fold (90% CI [2.03-2.63]) and 1.6-fold (90% CI

[1.42-1.84]), respectively. Since the interaction has not been established with dosages higher than

0.5 mg for repaglinide, the concomitant use of deferasirox with repaglinide should be avoided. If the

combination appears necessary, careful clinical and blood glucose monitoring should be performed

(see section 4.4). An interaction between deferasirox and other CYP2C8 substrates like paclitaxel

cannot be excluded.

In a healthy volunteer study, the concomitant administration of EXJADE as a CYP1A2 inhibitor

(repeated dose of 30 mg/kg/day) and the CYP1A2 substrate theophylline (single dose of 120 mg)

resulted in an increase of theophylline AUC by 84% (90% CI: 73% to 95%). The single dose C

not affected, but an increase of theophylline C

is expected to occur with chronic dosing. Therefore,

the concomitant use of EXJADE with theophylline is not recommended. If EXJADE and theophylline

are used concomitantly, monitoring of theophylline concentration and theophylline dose reduction

should be considered. An interaction between EXJADE and other CYP1A2 substrates cannot be

excluded. For substances that are predominantly metabolised by CYP1A2 and that have a narrow

therapeutic index (e.g. clozapine, tizanidine), the same recommendations apply as for theophylline.

The concomitant administration of EXJADE and aluminium-containing antacid preparations has not

been formally studied. Although deferasirox has a lower affinity for aluminium than for iron, it is not

recommended to take EXJADE tablets with aluminium-containing antacid preparations.

The concomitant administration of EXJADE and vitamin C has not been formally studied. Doses of

vitamin C up to 200 mg per day have not been associated with adverse consequences.

No interaction was observed between EXJADE and digoxin in healthy adult volunteers.

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4.6

Fertility, pregnancy and lactation

Pregnancy

No clinical data on exposed pregnancies are available for deferasirox. Studies in animals have shown

some reproductive toxicity at maternally toxic doses (see section 5.3). The potential risk for humans is

unknown.

As a precaution, it is recommended that EXJADE is not used during pregnancy unless clearly

necessary.

EXJADE may decrease the efficacy of hormonal contraceptives (see section 4.5).

Breast-feeding

In animal studies, deferasirox was found to be rapidly and extensively secreted into maternal milk. No

effect on the offspring was noted. It is not known if deferasirox is secreted into human milk. Breast-

feeding while taking EXJADE is not recommended.

Fertility

No fertility data is available for humans. In animals, no adverse effects on male or female fertility

were found (see section 5.3).

4.7

Effects on ability to drive and use machines

No studies on the effects of EXJADE on the ability to drive and use machines have been performed.

Patients experiencing the uncommon adverse reaction of dizziness should exercise caution when

driving or operating machinery (see section 4.8).

4.8

Undesirable effects

Summary of the safety profile

The most frequent reactions reported during chronic treatment with EXJADE in adult and paediatric

patients include gastrointestinal disturbances in about 26% of patients (mainly nausea, vomiting,

diarrhoea or abdominal pain) and skin rash in about 7% of patients. Diarrhoea is reported more

commonly in paediatric patients aged 2 to 5 years and in the elderly. These reactions are dose-

dependent, mostly mild to moderate, generally transient and mostly resolve even if treatment is

continued.

During clinical trials, increases in serum creatinine of >33% on two or more consecutive occasions,

sometimes above the upper limit of the normal range, occurred in about 36% of patients. These were

dose-dependent. About two-thirds of the patients showing serum creatinine increase returned below

the 33% level without dose adjustment. In the remaining third the serum creatinine increase did not

always respond to a dose reduction or a dose interruption. Indeed, in some cases, only a stabilisation

of the serum creatinine values has been observed after dose reduction (see section 4.4).

In a retrospective meta-analysis of 2,102 adult and paediatric beta-thalassaemia patients with

transfusional iron overload (including patients with different characteristics such as transfusion

intensity, posology and treatment duration) treated in two randomised clinical trials and four open

label studies of up to five years’ duration, a mean creatinine clearance decrease of 13.2% in adult

patients (95% CI: -14.4% to -12.1%; n=935) and 9.9% (95% CI: -11.1% to -8.6%; n=1,142) in

paediatric patients was observed during the first year of treatment. In a subset of patients followed for

more than one year (n=250 up to five years), no further decrease in mean creatinine clearance levels

was observed in subsequent years.

In a 1-year, randomised, double-blind, placebo-controlled study in patients with non-transfusion-

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dependent thalassaemia syndromes and iron overload, diarrhoea (9.1%), rash (9.1%), and nausea

(7.3%) were the most frequent study drug-related adverse events reported by patients receiving

10 mg/kg/day of EXJADE. Abnormal serum creatinine and creatinine clearance values were reported

in 5.5% and 1.8%, respectively, of patients receiving 10 mg/kg/day of EXJADE. Elevations of liver

transaminases greater than 2 times the baseline and 5 times the upper limit of normal were reported in

1.8% of patients treated with 10 mg/kg/day of EXJADE.

Tabulated list of adverse reactions

Adverse reactions are ranked below using the following convention: very common (≥1/10); common

(≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare

(<1/10,000); not known (cannot be estimated from the available data). Within each frequency

grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1

Blood and lymphatic system disorders

Not known:

Pancytopenia

, thrombocytopenia

, anaemia aggravated

neutropenia

Immune system disorders

Not known:

Hypersensitivity reactions (including anaphylaxis and angioedema)

Metabolism and nutrition disorders

Not known:

Metabolic acidosis

Psychiatric disorders

Uncommon:

Anxiety, sleep disorder

Nervous system disorders

Common:

Headache

Uncommon:

Dizziness

Eye disorders

Uncommon:

Early cataract, maculopathy

Rare:

Optic neuritis

Ear and labyrinth disorders

Uncommon:

Hearing loss

Respiratory, thoracic and mediastinal disorders

Uncommon:

Pharyngolaryngeal pain

Gastrointestinal disorders

Common:

Diarrhoea, constipation, vomiting, nausea, abdominal pain,

abdominal distension, dyspepsia

Uncommon:

Gastrointestinal haemorrhage, gastric ulcer (including multiple

ulcers), duodenal ulcer, gastritis

Rare:

Oesophagitis

Not known:

Gastrointestinal perforation

Hepatobiliary disorders

Common:

Transaminases increased

Uncommon:

Hepatitis, cholelithiasis

Not known:

Hepatic failure

Skin and subcutaneous tissue disorders

Common:

Rash, pruritus

Uncommon:

Pigmentation disorder

Not known:

Stevens-Johnson syndrome

, leukocytoclastic vasculitis

, urticaria

erythema multiforme

, alopecia

Renal and urinary disorders

Very common:

Blood creatinine increased

Common:

Proteinuria

Uncommon:

Renal tubulopathy (acquired Fanconi’s syndrome), glycosuria

Not known:

Acute renal failure

, tubulointerstitial nephritis

, nephrolithiasis,

renal tubular necrosis

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General disorders and administration site conditions

Uncommon:

Pyrexia, oedema, fatigue

Adverse reactions reported during post-marketing experience. These are derived from

spontaneous reports for which it is not always possible to reliably establish frequency or a

causal relationship to exposure to the medicinal product.

Gallstones and related biliary disorders were reported in about 2% of patients. Elevations of liver

transaminases were reported as an adverse reaction in 2% of patients. Elevations of transaminases

greater than 10 times the upper limit of the normal range, suggestive of hepatitis, were uncommon

(0.3%). During post-marketing experience, hepatic failure, sometimes fatal, has been reported with

EXJADE, especially in patients with pre-existing liver cirrhosis (see section 4.4). There have been

post-marketing reports of metabolic acidosis. The majority of these patients had renal impairment,

renal tubulopathy (Fanconi’s syndrome) or diarrhoea, or conditions where acid-base imbalance is a

known complication (see section 4.4). Serious acute pancreatitis may potentially occur as a

complication of gallstones (and related biliary disorders). As with other iron chelator treatment, high-

frequency hearing loss and lenticular opacities (early cataracts) have been uncommonly observed in

patients treated with EXJADE (see section 4.4).

Paediatric population

Diarrhoea is reported more commonly in paediatric patients aged 2 to 5 years than in older patients.

Renal tubulopathy has been mainly reported in children and adolescents with beta-thalassaemia

treated with EXJADE.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It

allows continued monitoring of the benefit/risk balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health according to the

National Regulation by using an online form

(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.h

ealth.gov.il ).

4.9

Overdose

Cases of overdose (2-3 times the prescribed dose for several weeks) have been reported. In one case,

this resulted in subclinical hepatitis which resolved after a dose interruption. Single doses of 80 mg/kg

in iron-overloaded thalassaemic patients caused mild nausea and diarrhoea.

Acute signs of overdose may include nausea, vomiting, headache and diarrhoea. Overdose may be

treated by induction of emesis or by gastric lavage, and by symptomatic treatment.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Iron chelating agent, ATC code: V03AC03

Mechanism of action

Deferasirox is an orally active chelator that is highly selective for iron (III). It is a tridentate ligand

that binds iron with high affinity in a 2:1 ratio. Deferasirox promotes excretion of iron, primarily in

the faeces. Deferasirox has low affinity for zinc and copper, and does not cause constant low serum

levels of these metals.

Pharmacodynamic effects

In an iron-balance metabolic study in iron-overloaded adult thalassaemic patients, EXJADE at daily

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doses of 10, 20 and 40 mg/kg induced the mean net excretion of 0.119, 0.329 and 0.445 mg Fe/kg

body weight/day, respectively.

Clinical efficacy and safety

EXJADE has been investigated in 411 adult (age

16 years) and 292 paediatric patients (aged 2 to

<16 years) with chronic iron overload due to blood transfusions. Of the paediatric patients 52 were

aged 2 to 5 years. The underlying conditions requiring transfusion included beta-thalassaemia, sickle

cell disease and other congenital and acquired anaemias (myelodysplastic syndromes, Diamond-

Blackfan syndrome, aplastic anaemia and other very rare anaemias).

Daily treatment at doses of 20 and 30 mg/kg for one year in frequently transfused adult and paediatric

patients with beta-thalassaemia led to reductions in indicators of total body iron; liver iron

concentration was reduced by about -0.4 and -8.9 mg Fe/g liver (biopsy dry weight (dw)) on average,

respectively, and serum ferritin was reduced by about -36 and -926 µg/l on average, respectively. At

these same doses the ratios of iron excretion : iron intake were 1.02 (indicating net iron balance) and

1.67 (indicating net iron removal), respectively. EXJADE induced similar responses in iron-

overloaded patients with other anaemias. Daily doses of 10 mg/kg for one year could maintain liver

iron and serum ferritin levels and induce net iron balance in patients receiving infrequent transfusions

or exchange transfusions. Serum ferritin assessed by monthly monitoring reflected changes in liver

iron concentration indicating that trends in serum ferritin can be used to monitor response to therapy.

Limited clinical data (29 patients with normal cardiac function at baseline) using MRI indicate that

treatment with EXJADE 10-30 mg/kg/day for 1 year may also reduce levels of iron in the heart (on

average, MRI T2* increased from 18.3 to 23.0 milliseconds).

The principal analysis of the pivotal comparative study in 586 patients suffering from beta-

thalassaemia and transfusional iron overload did not demonstrate non-inferiority of EXJADE to

deferoxamine in the analysis of the total patient population. It appeared from a post-hoc analysis of

this study that, in the subgroup of patients with liver iron concentration ≥7 mg Fe/g dw treated with

EXJADE (20 and 30 mg/kg) or deferoxamine (35 to ≥50 mg/kg), the non-inferiority criteria were

achieved. However, in patients with liver iron concentration <7 mg Fe/g dw treated with EXJADE (5

and 10 mg/kg) or deferoxamine (20 to 35 mg/kg), non-inferiority was not established due to

imbalance in the dosing of the two chelators. This imbalance occurred because patients on

deferoxamine were allowed to remain on their pre-study dose even if it was higher than the protocol

specified dose. Fifty-six patients under the age of 6 years participated in this pivotal study, 28 of them

receiving EXJADE.

It appeared from preclinical and clinical studies that EXJADE could be as active as deferoxamine

when used in a dose ratio of 2:1 (i.e. a dose of EXJADE that is numerically half of the deferoxamine

dose). However, this dosing recommendation was not prospectively assessed in the clinical trials.

In addition, in patients with liver iron concentration ≥7 mg Fe/g dw with various rare anaemias or

sickle cell disease, EXJADE up to 20 and 30 mg/kg produced a decrease in liver iron concentration

and serum ferritin comparable to that obtained in patients with beta-thalassaemia.

In patients with non-transfusion-dependent thalassaemia syndromes and iron overload, treatment with

EXJADE was assessed in a 1-year, randomised, double-blind, placebo-controlled study. The study

compared the efficacy of two different deferasirox regimens (starting doses of 5 and 10 mg/kg/day,

55 patients in each arm) and of matching placebo (56 patients). The study enrolled 145 adult and 21

paediatric patients. The primary efficacy parameter was the change in liver iron concentration (LIC)

from baseline after 12 months of treatment. One of the secondary efficacy parameters was the change

in serum ferritin between baseline and fourth quarter. At a starting dose of 10 mg/kg/day, EXJADE

led to reductions in indicators of total body iron. On average, liver iron concentration decreased by

3.80 mg Fe/g dw in patients treated with EXJADE (starting dose 10 mg/kg/day) and increased by

0.38 mg Fe/g dw in patients treated with placebo (p<0.001). On average, serum ferritin decreased by

222.0 µg/l in patients treated with EXJADE (starting dose 10 mg/kg/day) and increased by 115 µg/l in

patients treated with placebo (p<0.001).

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The European Medicines Agency has deferred the obligation to submit the results of studies with

EXJADE in one or more subsets of the paediatric population in the treatment of chronic iron overload

requiring chelation therapy (see section 4.2 for information on paediatric use).

5.2

Pharmacokinetic properties

Absorption

Deferasirox is absorbed following oral administration with a median time to maximum plasma

concentration (t

) of about 1.5 to 4 hours. The absolute bioavailability (AUC) of deferasirox from

EXJADE tablets is about 70% compared to an intravenous dose. Total exposure (AUC) was

approximately doubled when taken along with a high-fat breakfast (fat content >50% of calories) and

by about 50% when taken along with a standard breakfast. The bioavailability (AUC) of deferasirox

was moderately (approx. 13–25%) elevated when taken 30 minutes before meals with normal or high

fat content.

Distribution

Deferasirox is highly (99%) protein bound to plasma proteins, almost exclusively serum albumin, and

has a small volume of distribution of approximately 14 litres in adults.

Biotransformation

Glucuronidation is the main metabolic pathway for deferasirox, with subsequent biliary excretion.

Deconjugation of glucuronidates in the intestine and subsequent reabsorption (enterohepatic

recycling) is likely to occur: in a healthy volunteer study, the administration of cholestyramine after a

single dose of deferasirox resulted in a 45% decrease in deferasirox exposure (AUC).

Deferasirox is mainly glucuronidated by UGT1A1 and to a lesser extent UGT1A3. CYP450-catalysed

(oxidative) metabolism of deferasirox appears to be minor in humans (about 8%). No inhibition of

deferasirox metabolism by hydroxyurea was observed in vitro.

Elimination

Deferasirox and its metabolites are primarily excreted in the faeces (84% of the dose). Renal

excretion of deferasirox and its metabolites is minimal (8% of the dose). The mean elimination half-

life (t

) ranged from 8 to 16 hours. The transporters MRP2 and MXR (BCRP) are involved in the

biliary excretion of deferasirox.

Linearity / non-linearity

The C

and AUC

0-24h

of deferasirox increase approximately linearly with dose under steady-state

conditions. Upon multiple dosing exposure increased by an accumulation factor of 1.3 to 2.3.

Characteristics in patients

Paediatric patients

The overall exposure of adolescents (12 to ≤17

years) and children (2 to <12 years) to deferasirox

after single and multiple doses was lower than that in adult patients. In children younger than 6 years

old exposure was about 50% lower than in adults. Since dosing is individually adjusted according to

response this is not expected to have clinical consequences.

Gender

Females have a moderately lower apparent clearance (by 17.5%) for deferasirox compared to males.

Since dosing is individually adjusted according to response this is not expected to have clinical

consequences.

Elderly patients

The pharmacokinetics of deferasirox have not been studied in elderly patients (aged 65 or older).

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Renal or hepatic impairment

The pharmacokinetics of deferasirox have not been studied in patients with renal impairment. The

pharmacokinetics of deferasirox were not influenced by liver transaminase levels up to 5 times the

upper limit of the normal range.

In a clinical study using single doses of 20 mg/kg deferasirox, the average exposure was increased by

16% in subjects with mild hepatic impairment (Child-Pugh Class A) and by 76% in subjects with

moderate hepatic impairment (Child-Pugh Class B) compared to subjects with normal hepatic

function. The average C

of deferasirox in subjects with mild or moderate hepatic impairment was

increased by 22%. Exposure was increased 2.8-fold in one subject with severe hepatic impairment

(Child-Pugh Class C) (see sections 4.2 and 4.4).

5.3

Preclinical safety data

Preclinical data reveal no special hazard for patients with iron overload, based on conventional studies

of safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenic potential. The main

findings were kidney toxicity and lens opacity (cataracts). Similar findings were observed in neonatal

and juvenile animals. The kidney toxicity is considered mainly due to iron deprivation in animals that

were not previously overloaded with iron.

Tests of genotoxicity in vitro were either negative (Ames test, chromosomal aberration test) or

positive (V79 screen). Deferasirox caused formation of micronuclei in vivo in the bone marrow, but

not liver, of non-iron-loaded rats at lethal doses. No such effects were observed in iron-preloaded rats.

Deferasirox was not carcinogenic when administered to rats in a 2-year study and transgenic p53+/-

heterozygous mice in a 6-month study.

The potential for toxicity to reproduction was assessed in rats and rabbits. Deferasirox was not

teratogenic, but caused increased frequency of skeletal variations and stillborn pups in rats at high

doses that were severely toxic to the non-iron-overloaded mother. Deferasirox did not cause other

effects on fertility or reproduction.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Crospovidone

Lactose monohydrate (200 mesh)

Lactose monohydrate (spray dried)

Microcrystalline cellulose (NF) / Cellulose, microcrystalline (Ph. Eur.)

Povidone (K30)

Sodium lauril sulfate

Colloidal silicone dioxide (NF) / Silica, colloidal anhydrous (Ph. Eur.)

Magnesium stearate

6.2

Incompatibilities

Dispersion in carbonated drinks or milk is not recommended due to foaming and slow dispersion,

respectively.

6.4

Special precautions for storage

Do not store above 30°C.

EXJ API DEC15 CL V11 COR DEC15 CL

REF SmPC APR15

Store in the original package in order to protect from moisture.

6.5

Nature and contents of container

PVC/PE/PVDC/Aluminium blisters.

Packs containing 28 or 84 dispersible tablets.

Not all pack sizes may be marketed.

6.6

Special precautions for disposal

No special requirements.

7.

REGISTRATION LICENSE HOLDER

Novartis Israel Ltd., 36 Shacham St.,Petach-Tikva.

8.

REGISTRATION NUMBER(S)

Exjade 125mg: 133 99 31337

Exjade 250mg: 134 02 31338

Exjade 500mg: 134 01 31339

9. MANUFACTURER

Novartis Pharma Stein AG., Stein, Switzerland.

For: Novartis Pharma AG, Basel, Switzerland

אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה ןכדועמ(

05.2013

:ךיראת

22.1.2013

.

:םושירה רפסמו תילגנאב רישכת םש

[

31337-9

]

Exjade 125mg, 250mg, 500mg dispersible tablets

,

:םושירה לעב םש

Novartis Pharma Services AG

.

! דבלב תורמחהה טורפל דעוימ הז ספוט תושקובמה תורמחהה ןולעב קרפ יחכונ טסקט שדח טסקט

Warnings and

precautions

Skin

Skin disorders

Cases of Stevens-Johnson syndrome )SJS(

have been reported during the post-

marketing period. If SJS is suspected

EXJADE should be discontinued.

Warnings and

precautions

Skin

Skin rashes may appear during Exjade

treatment. For rashes of mild to moderate

severity, Exjade may be continued without

dose adjustment, since the rash often

resolves spontaneously. For more severe

rash, where interruption of treatment may

be necessary, Exjade may be reintroduced

after resolution of the rash at a lower dose,

followed by gradual dose escalation. In

severe cases, this reintroduction may be

conducted in combination with a short

course of oral corticosteroids.

Rare cases of erythema multiforme have

been reported during EXJADE treatment.

Skin disorders

Rare cases of erythema multiforme have

been reported during EXJADE treatment.

Skin rashes may appear during Exjade

treatment. For rashes of mild to moderate

severity, Exjade may be continued without

dose adjustment, since the rash often

resolves spontaneously. For more severe

rash, where interruption of treatment may

be necessary, Exjade may be reintroduced

after resolution of the rash at a lower dose,

followed by gradual dose escalation. In

severe cases, this reintroduction may be

conducted in combination with a short

course of oral corticosteroids.

תושקובמה תורמחהה

Adverse drug

reactions

Table 2

Adverse drug reactions

derived from spontaneous reports

חפסנב תפרוצמ הלבט ואר אנא

Table 2

Adverse drug reactions

derived from spontaneous reports

חפסנב תפרוצמ הלבט ואר אנא

Women

of

child-bearing

potential,

p

regnancy

and

breast-

feeding

and

fertility

Pregnancy and breast-feeding

Pregnancy

There have been no controlled clinical

studies of the use of deferasirox during

pregnancy. Studies in animals have shown

some reproductive toxicity at maternally

toxic doses )see Non-clinical safety data(.

The potential risk for humans is unknown.

It is therefore recommended that Exjade

should not be used during pregnancy

unless absolutely necessary.

Breast-feeding

In animal studies deferasirox was found to

be rapidly and extensively secreted into

milk. No effect on the offspring was

noted. It is not known if deferasirox passes

into human milk. Breastfeeding is not

recommended during treatment with

Exjade.

Women of child-bearing potential

Animal studies showed that deferasirox

was not teratogenic in rats or rabbits, but

caused increased frequency of skeletal

variations and stillborn pups in rats at high

doses that were severely toxic to the non-

iron-overloaded mother. Deferasirox did

not cause other effects on fertility or

reproduction )see section 13 Non-clinical

safety data(. The potential risk for humans

is unknown.

Caution

should

exercised

when

deferasirox is combined with hormonal

contraceptive agents that are metaboliszed

through CYP3A4 due to a possible

decrease in efficacy of contraceptive

agents )see section 8 Interactions(.

Fertility

EXJADE did not affect fertility or

reproduction in rat studies even at toxic

doses )see section 13 Non-clinical safety

data(.

Pregnancy

There have been no controlled clinical

studies of the use of deferasirox during

pregnancy. Studies in animals have shown

some reproductive toxicity at maternally

toxic doses )see Non-clinical safety data(.

The potential risk for humans is unknown.

It is therefore recommended that Exjade

should not be used during pregnancy

unless absolutely necessary.

Breast-feeding

In animal studies deferasirox was found to

be rapidly and extensively secreted into

maternal milk. No effects on the offspring

were noted at maternally non-toxic doses

of deferasirox. It is not known if

deferasirox passes into human milk.

Breastfeeding is not recommended during

treatment with Exjade.

תושקובמה תורמחהה חפסנ

Table 2Adverse drug reactions derived from spontaneous reports

Renal and urinary disorders

Cases of acute renal failure )mostly serum creatinine increased ≥ 2x upper limit of

normal, and usually reversible after treatment interruption(, some with fatal

outcome have been described , tubulointerstitial nephritis

Hepatobiliary disorders

hepatic failure

Skin and subcutaneous tissue disorders

leukocytoclastic vasculitis, urticaria, alopecia

Immune system disorders

hypersensitivity reactions )including anaphylaxis and angioedema, urticaria(

חפסנ

Table 2Adverse drug reactions derived from spontaneous reports

Renal and urinary disorders

Cases of acute renal failure )mostly serum creatinine increased ≥ 2x upper limit of

normal, and usually reversible after treatment interruption(, some with fatal

outcome have been described , tubulointerstitial nephritis.

Hepatobiliary disorders

hepatic failure.

Skin and subcutaneous tissue disorders

Stevens-Johnson syndrome, leukocytoclastic vasculitis, urticaria, alopecia.

Immune system disorders

hypersensitivity reactions )including anaphylaxis and angioedema, urticaria(.

ןכרצל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה ןכדועמ(

05.2013

:ךיראת

22.1.2013

.

:םושירה רפסמו תילגנאב רישכת םש

[

31337-9

]

Exjade 125mg, 250mg, 500mg dispersible tablets

,

:םושירה לעב םש

Novartis Pharma Services AG

.

! דבלב תורמחהה טורפל דעוימ הז ספוט תושקובמה תורמחהה ןולעב קרפ יחכונ טסקט שדח טסקט תודחוימ תורהזא שומישב תועגונה הפורתב

אפורה תא עדייל שי

תווצ שיא וא חקורה יאופר ידיימ ןפואב הדימב וא דחאב שח התאו

םיאבה םימוטפמיסהמ רתוי תליטנ ךלהמב דיי'גסקא

םד איקמ התאו הדימב

האוצ ךל שי וא הרוחש

שח התא םא ןטב באכ וא תורידת תוברצ ליטנ וא הליכא רחאל דוחייב )םיביכ(

.דיי'גסקא

ןיחבמ התא םא ןתש ןתמב הרומח הדיריב .)תוילכב היעבל ןמיס(

הרומח החירפ ךל שי םא

המישנ יישק וא םינפה לש רקיעב תוחיפנ וא תרוחרחסו תיגרלא הבוגת לש םינמיס( ןורגהו )הרומח

,רועה לש המדאה ,החירפ ךל שי םא ,הפ וא םייניע ,םייתפשה לע תויחופלש לש םינמיס( ןורג באכ ,רועה לש ףוליק )הפירח רוע תבוגת

דצב באכ ,םונמנ לש בוליש שח התא םא היילע וא הבהצה ,ןטבה לש ינמיה ןוילעה ההכ ןתשו םיינעה וא רועה תבהצהב .)דבכב תויעב לש םינמיס( :בקעמו תוקידב הפורתב לופיטה ךלהמבו לופיטה תליחת ינפל ,רידס ןפואב )ןתשו םד( תוקידב רובעל ךילע וז תומר( ךפוגב לזרבה תמר רחא בקעמ ךרוצל עיפשמ ד'ייגסקא םאה ןוחבל ידכ )ןיטירפ רחא בקעמב םג ועייסי ולא תוקידב .שרדנכ תוחכונ ,םדב ןיניטאירק תומר( תוילכה ידוקפת תומר( דבכה ידוקפתו )ןתשב ןובלח ןיילקלאו ןיבוריליב ,םדב תוזנימאסנארט תוקידב תואצותב בשחתי אפורה .)זאטפסופ דיי'גסקא לש ןונימ הזיא טילחי רשאכ ולא .רתויב ךל םיאתמ הפורתב לופיטה ךלהמבו לופיטה תליחת ינפל םד( תוקידב רובעל ךילע וז

ןתש

וא הימדה

והת [ תיטנגמ הד

רידס ןפואב

תוקידב ורטני ולא רחא בקעמ ךרוצל תא לזרבה תמר ןיטירפ תומר( ךפוגב

וא/ו דבכב לזרב תלוכת בלב עיפשמ ד'ייגסקא םאה ןוחבל ידכ ) רחא בקעמב םג ועייסי ולא תוקידב .שרדנכ תוחכונ ,םדב ןיניטאירק תומר( תוילכה ידוקפת תומר( דבכה ידוקפתו )ןתשב ןובלח ןיילקלאו ןיבוריליב ,םדב תוזנימאסנארט תוקידב תואצותב בשחתי אפורה .)זאטפסופ דיי'גסקא לש ןונימ הזיא טילחי רשאכ ולא רתויב ךל םיאתמ

ולא תוקידבב שמתשי ןכו טילחהל ידכ

לופיטה תא קיספהל יתמ דיי'גסקאב

יאוול תועפות

ו דיי'גסקא לוטיל קיספהל שי

תלבקל תונפ םא ידיימ ןפואב תיאופר הרזע םירקמה דחא לע וא ךילע םילח םיאבה ךדלי

הבוגת לע עיבצהל םילוכיה םימוטפמיס :תיגרלא

העילב וא המישנ יישק

יתפשה ,םינפה לש תוחפנתה

ןושלה ,ם ןורגה וא

וא המודא החירפ םע ,רועב רומח דרג תומרומ תוטילב

יאוול תועפות

הפורתה תא לוטיל קיספהל שי :םיאבה םירקמב אפורל דימ חוודלו

הפורתה תא לוטיל קיספהל שי :םיאבה םירקמב אפורל דימ חוודלו תועפות עיפשהל תולולע( תוחיכש אל יאוול לכב דחא לפוטמ דע תוחפ לע

100

)םילפוטמ

ןטבה לש ינמיה דצב וא בגב ימואתפ באכ

םינבאל םינמי )הרמה סיכב תושקובמה תורמחהה תונמוסמ ובש ,ןולעה ב"צמ בוהצ עקר לע

.

ונמוס תורמחה רדגב םניאש םייוניש )ןולעב( םוקימב םייוניש אלו יתוהמ ןכות קר ןמסל שי .הנוש עבצב .טסקטה

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