Deferasirox Accord

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Deferasirox Accord 90 mg film-coated tablets  
Deferasirox Accord 180 mg film-coated tablets  
Deferasirox Accord 360 mg film-coated tablets  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Deferasirox Accord 90 mg film-coated tablets 
 
Each film-coated tablet contains 90 mg deferasirox. 
 
Excipients with known effect 
Each 90 mg tablet also contains 27 mg of lactose (as monohydrate) and 2.95 mg of castor oil. 
 
Deferasirox Accord 180 mg film-coated tablets 
 
Each film-coated tablet contains 180 mg deferasirox. 
 
Excipients with known effect 
Each 180 mg tablet also contains 54 mg of lactose (as monohydrate) and 5.9 mg of castor oil. 
 
Deferasirox Accord 360 mg film-coated tablets 
 
Each film-coated tablet contains 360 mg deferasirox.  
 
Excipients with known effect 
Each 360 mg tablet also contains 108 mg of lactose (as monohydrate) and 11.8 mg of castor oil. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet 
 
Deferasirox Accord 90 mg film-coated tablets 
 
Yellow colored, film coated oval, biconvex tablets with beveled edges debossed with ‘D’ on one side 
and ‘90’ on another side. Approximate tablet dimensions 11.0 mm x 4.20 mm. 
 
Deferasirox Accord 180 mg film-coated tablets 
 
Yellow colored, film coated oval, biconvex tablets with beveled edges debossed with ‘D’ on one side 
and ‘180’ on another side. Approximate tablet dimensions 14.0 mm x 5.50 mm. 
 
Deferasirox Accord 360 mg film-coated tablets 
 
Yellow colored, film coated oval, biconvex tablets with beveled edges debossed with ‘D’ on one side 
and ‘360’ on another side. Approximate tablet dimensions 17.0 mm x 6.80 mm. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 



3 

Deferasirox Accord is indicated for the treatment of chronic iron overload due to frequent blood 
transfusions (≥7 ml/kg/month of packed red blood cells) in patients with beta thalassaemia major aged 
6 years and older. 
 
Deferasirox Accord is also indicated for the treatment of chronic iron overload due to blood 
transfusions when deferoxamine therapy is contraindicated or inadequate in the following patient 
groups: 
- in paediatric patients with beta thalassaemia major with iron overload due to frequent blood 

transfusions (≥7 ml/kg/month of packed red blood cells) aged 2 to 5 years, 
- in adult and paediatric patients with beta thalassaemia major with iron overload due to 

infrequent blood transfusions (<7 ml/kg/month of packed red blood cells) aged 2 years and 
older, 

- in adult and paediatric patients with other anaemias aged 2 years and older. 
 
Deferasirox Accord is also indicated for the treatment of chronic iron overload requiring chelation 
therapy when deferoxamine therapy is contraindicated or inadequate in patients with non-transfusion-
dependent thalassaemia syndromes aged 10 years and older. 
 
4.2 Posology and method of administration 
 
Treatment with deferasirox should be initiated and maintained by physicians experienced in the 
treatment of chronic iron overload. 
 
Deferasirox Accord is only available as film-coated tablets. 
All references to the dispersible tablet formulation throughout the SmPC refer to the reference 
medical product dispersible tablets. 
 
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 (PRBC) 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. 
 
Caution should be taken during chelation therapy to minimise the risk of overchelation in all patients 
(see section 4.4). 
 
Deferasirox film-coated tablets demonstrate higher bioavailability compared to the deferasirox 
dispersible tablet formulation (see section 5.2). In case of switching from dispersible tablets to film-
coated tablets, the dose of the film-coated tablets should be 30% lower than the dose of the dispersible 
tablets, rounded to the nearest whole tablet. 
 
Table 1 Recommended doses for transfusional iron overload 
 
 Film-coated tablets Transfusions Serum ferritin 
Starting dose 14 mg/kg/day After 20 units 

(about 100 ml/kg) 
of PRBC 

or >1,000 µg/l 

Alternative 
starting doses 

21 mg/kg/day >14 ml/kg/month 
of PRBC (approx. 
>4 units/month for 
an adult) 

 



4 

7 mg/kg/day <7 ml/kg/month 
of PRBC (approx. 
<2 units/month for 
an adult) 

 

For patients well 
managed on 
deferoxamine 

One third of deferoxamine dose   

Monitoring  Monthly 
Target range  500-1,000 µg/l 
Adjustment step 
(every 
3-6 month) 

Increase  
 

>2,500 µg/l 
3.5-7 mg/kg/day 
Up to 28 mg/kg/day 

Decrease  <2,500 µg/l 
3.5-7 mg/kg/day 
In patients treated with doses  
>21 mg/kg/day 
-When target is reached 500-1,000 µg/l  

Maximum dose 28 mg/kg/day   

Consider 
interruption 

 <500 µg/l 

 
Starting dose 
The recommended initial daily dose of deferasirox film-coated tablets is 14 mg/kg body weight. 
 
An initial daily dose of 21 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 7 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 deferasirox 
film-coated tablets that is numerically one third 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 14 mg/kg/day of deferasirox film-coated tablets). When this 
results in a daily dose less than 14 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 deferasirox be 
adjusted, if necessary, every 3 to 6 months based on the trends in serum ferritin. Dose adjustments 
may be made in steps of 3.5 to 7 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 21 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 28 mg/kg may be considered. The availability of long-term 
efficacy and safety data from clinical studies conducted with deferasirox dispersible tablets 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 21 mg/kg, a further 
increase (to a maximum of 28 mg/kg) may not achieve satisfactory control, and alternative treatment 
options may be considered. If no satisfactory control is achieved at doses above 21 mg/kg, treatment at 
such doses should not be maintained and alternative treatment options should be considered whenever 



5 

possible. Doses above 28 mg/kg are not recommended because there is only limited experience with 
doses above this level (see section 5.1). 
 
In patients treated with doses greater than 21 mg/kg, dose reductions in steps of 3.5 to 7 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 3.5 to 7 mg/kg should be 
considered to maintain serum ferritin levels within the target range and to minimise the risk of 
overchelation. If serum ferritin falls consistently below 500 µg/l, an interruption of treatment should 
be considered (see section 4.4). 
 
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 overchelation in all patients (see 
section 4.4). 
 
Deferasirox film-coated tablets demonstrate higher bioavailability compared to the deferasirox 
dispersible tablet formulation (see section 5.2). In case of switching from dispersible tablets to film-
coated tablets, the dose of the film-coated tablets should be 30% lower than the dose of the dispersible 
tablets, rounded to the nearest whole tablet. 
 
Table 2 Recommended doses for non-transfusion-dependent thalassaemia syndromes 
 
 Film-coated tablets Liver iron 

concentration 
(LIC)* 

Serum ferritin 

Starting dose 7 mg/kg/day ≥5 mg Fe/g dw or >800 µg/l 
Monitoring  Monthly 
Adjustment steps 
(every 3-
6 months) 

Increase 
≥7 mg Fe/g dw >2,000 µg/l 3.5-7 mg/kg/day 

Decrease <7 mg Fe/g dw ≤2,000 µg/l 3.5-7 mg/kg/day 
Maximum dose 14 mg/kg/day   

7 mg/kg/day   
For adults 

For paediatric patients not assessed and ≤2,000 µg/l 

Interruption  <3 mg Fe/g dw or <300 µg/l 

Retreatment  Not recommended 
 
* LIC is the preferred method of iron overload determination. 
 
Starting dose 
The recommended initial daily dose of deferasirox film-coated tablets in patients with non-transfusion-
dependent thalassaemia syndromes is 7 mg/kg body weight. 
 
Dose adjustment 
It is recommended that serum ferritin be monitored every month to assess the patient’s response to 
therapy and to minimise the risk of overchelation (see section 4.4). After every 3 to 6 months of 
treatment, a dose increase in increments of 3.5 to 7 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 14 mg/kg are not recommended 



6 

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 
7 mg/kg. 
 
For patients in whom the dose was increased to >7 mg/kg, dose reduction to 7 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 (≥65 years of age) 
The dosing recommendations for elderly patients are the same as described above. In clinical studies, 
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. 
 
Renal impairment 
Deferasirox 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). 
 
Hepatic impairment 
Deferasirox 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 
reduced followed by progressive increase up to a limit of 50% (see sections 4.4 and 5.2), and 
deferasirox 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). 
 
Paediatric population 
 
Transfusional iron overload: 
The dosing recommendations for paediatric patients aged 2 to 17 years with transfusional iron 
overload are the same as for adult patients (see section 4.2). It is recommended that serum ferritin be 
monitored every month to assess the patient’s response to therapy and to minimise the risk of 
overchelation (see section 4.4). 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. 
 
Non-transfusion-dependent thalassaemia syndromes: 
In paediatric patients with non-transfusion-dependent thalassaemia syndromes, dosing should not 
exceed 7 mg/kg. In these patients, closer monitoring of LIC and serum ferritin is essential to avoid 
overchelation (see section 4.4). In addition to monthly serum ferritin assessments, LIC should be 
monitored every three months when serum ferritin is ≤800 µg/l. 
 
Children from birth to 23 months: 
The safety and efficacy of deferasirox in children from birth to 23 months of age have not been 
established. No data are available. 



7 

 
Method of administration 
  
For oral use. 
 
The film-coated tablets should be swallowed whole with some water. For patients who are unable to 
swallow whole tablets, the film-coated tablets may be crushed and administered by sprinkling the full 
dose onto soft food, e.g. yogurt or apple sauce (pureed apple). The dose should be immediately and 
completely consumed, and not stored for future use. 
 
The film-coated tablets should be taken once a day, preferably at the same time each day, and may be 
taken on an empty stomach or with a light meal (see sections 4.5 and 5.2). 
 
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 
 
Deferasirox has been studied only in patients with baseline serum creatinine within the age-appropriate 
normal range. 
 
During clinical studies, 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. In some cases, only a stabilisation of the serum 
creatinine values has been observed after dose reduction. Cases of acute renal failure have been reported 
following post-marketing use of deferasirox (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 
deferasirox 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 reactions as observed after dose 
escalation of deferasirox dispersible tablets to doses above 30 mg/kg in clinical studies, an increased 
risk of renal adverse reactions with film-coated tablet doses above 21 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 prior to 
therapy, weekly in the first month after initiation or modification of therapy with deferasirox 
(including switch of formulation), 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 
deferasirox. The majority of these patients had renal impairment, renal tubulopathy (Fanconi 



8 

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 deferasirox 
therapy should be considered in patients who develop metabolic acidosis. 
 
Post-marketing cases of severe forms of renal tubulopathy (such as Fanconi syndrome) and renal failure 
associated with changes in consciousness in the context of hyperammonaemic encephalopathy have 
been reported in patients treated with deferasirox, mainly in children. It is recommended that 
hyperammonaemic encephalopathy be considered and ammonia levels measured in patients who 
develop unexplained changes in mental status while on deferasirox therapy. 
 
Table 3 Dose adjustment and interruption of treatment for renal monitoring 
 

 Serum creatinine  Creatinine clearance 
Before initiation of 
therapy 

Twice (2x) and Once (1x) 

Contraindicated   <60 ml/min 
Monitoring 
- First month after 

start of therapy or 
dose modification 
(including switch 
of formulation) 

- Thereafter 

 
Weekly 

 
 
 
 
 
Monthly 

 
and 

 
 
 
 
 
and 

 
Weekly 

 
 
 
 
 
Monthly 

Reduction of daily dose by 7 mg/kg/day (film-coated tablet formulation), 
if following renal parameters are observed at two consecutive visits and cannot be attributed to 
other causes 
Adult patients 

 
Paediatric patients 

>33% above pre- 
treatment average 
> age appropriate ULN** 

and 
 
and/or 

Decreases <LLN* (<90 ml/min) 
 
Decreases <LLN* (<90 ml/min) 

After dose reduction, interrupt treatment, if 
Adult and paediatric Remains >33% above 

pre-treatment average 
and/or Decreases <LLN* (<90 ml/min) 

*LLN: lower limit of the normal range 
**ULN: upper limit of the normal range 

 
Treatment may be reinitiated depending on the individual clinical circumstances. 
 
Dose reduction or interruption may be also considered if abnormalities occur in levels of markers of renal 
tubular function and/or as clinically indicated: 

• Proteinuria (test should be performed prior to therapy and monthly thereafter) 
• Glycosuria in non-diabetics and low levels of serum potassium, phosphate, magnesium or urate, 

phosphaturia, aminoaciduria (monitor as needed). 
• Renal tubulopathy has been mainly reported in children and adolescents with beta-thalassaemia 

treated with deferasirox. 
 
Patients should be referred to a renal specialist, and further specialised investigations (such as renal 
biopsy) may be considered if the following occur despite dose reduction and interruption: 

• Serum creatinine remains significantly elevated and 
• Persistent abnormality in another marker of renal function (e.g. proteinuria, Fanconi 

Syndrome). 
 
Hepatic function 
 
Liver function test elevations have been observed in patients treated with deferasirox. Post-marketing 
cases of hepatic failure, some of which were fatal, have been reported. Severe forms associated with 
changes in consciousness in the context of hyperammonaemic encephalopathy, may occur in patients 



9 

treated with deferasirox, particularly in children. It is recommended that hyperammonaemic 
encephalopathy be considered and ammonia levels measured in patients who develop unexplained 
changes in mental status while on deferasirox therapy. Care should be taken to maintain adequate 
hydration in patients who experience volume-depleting events (such as diarrhoea or vomiting), 
particularly in children with acute illness. Most reports of hepatic failure involved patients with 
significant morbidities including pre-existing liver cirrhosis. However, the role of deferasirox 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, 
deferasirox 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.  
 
Deferasirox is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) (see 
section 5.2). 
 
Table 4 Summary of safety monitoring recommendations 
 

Test Frequency 
Serum creatinine In duplicate prior to therapy. 

Weekly during first month of therapy or 
after dose modification (including switch of 
formulation). 
Monthly thereafter. 

Creatinine clearance and/or plasma 
cystatin C 

Prior to therapy. 
Weekly during first month of therapy or 
after dose modification (including switch of 
formulation). 
Monthly thereafter. 

Proteinuria Prior to therapy. 
Monthly thereafter. 

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 

Prior to therapy. 
Annually in paediatric patients. 

 

 
In patients with a short life expectancy (e.g. high-risk myelodysplastic syndromes), especially when 
co-morbidities could increase the risk of adverse reactions, the benefit of deferasirox might be limited 
and may be inferior to risks. As a consequence, treatment with deferasirox is not recommended in 
these patients. 
 
Caution should be used in elderly patients due to a higher frequency of adverse reactions (in 
particular, diarrhoea). 
 



10 

Data in children with non-transfusion-dependent thalassaemia are very limited (see section 5.1). As a 
consequence, deferasirox therapy should be closely monitored to detect adverse reactions and to 
follow iron burden in the paediatric population. In addition, before treating heavily iron-overloaded 
children with non-transfusion-dependent thalassaemia with deferasirox, the physician should be 
aware that the consequences of long-term exposure in such patients are currently not known. 
 
Gastrointestinal disorders 
 
Upper gastrointestinal ulceration and haemorrhage have been reported in patients, including children 
and adolescents, receiving deferasirox. 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 deferasirox 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 deferasirox 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/mm3 (50 x 109/l) (see section 4.5). 
 
Skin disorders 
 
Skin rashes may appear during deferasirox 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 be conducted in combination with a short period of oral steroid administration. Severe 
cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal 
necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), which could 
be life- threatening or fatal, have been reported. If any SCAR is suspected, deferasirox should be 
discontinued immediately and should not be reintroduced. At the time of prescription, patients should 
be advised of the signs and symptoms of severe skin reactions, and be closely monitored. 
 
Hypersensitivity reactions 
 
Cases of serious hypersensitivity reactions (such as anaphylaxis and angioedema) have been reported 
in patients receiving deferasirox, 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, deferasirox 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 deferasirox. 
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 



11 

 
Monthly monitoring of serum ferritin is recommended in order to assess the patient’s response to 
therapy and to avoid overchelation (see section 4.2). Dose reduction or closer monitoring of renal and 
hepatic function, and serum ferritin levels are recommended during periods of treatments with high 
doses and when serum ferritin levels are close to the target range. 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. 
 
In two clinical studies, growth and sexual development of paediatric patients treated with deferasirox 
for up to 5 years were not affected (see section 4.8). 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 prior to therapy and 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 deferasirox. 
 
Excipients 
 
Deferasirox Accord contains lactose. Patients with rare hereditary problems of galactose intolerance, 
total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’. 
 
Deferasirox Accord contains castor oil. This medicinal product may cause stomach upset and diarrhea. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
The safety of deferasirox 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). 
 
Interaction with food 
 
The Cmax of deferasirox film-coated tablets was increased (by 29%) when taken with a high-fat meal. 
Deferasirox film-coated tablets may be taken either on an empty stomach or with a light meal, 
preferably at the same time each day (see sections 4.2 and 5.2). 
 
Agents that may decrease deferasirox systemic exposure 
 
Deferasirox metabolism depends on UGT enzymes. In a healthy volunteer study, the concomitant 
administration of deferasirox (single dose of 30 mg/kg, dispersible tablet formulation) 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 deferasirox with potent 
UGT inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital, ritonavir) may result in a 
decrease in deferasirox efficacy. The patient’s serum ferritin should be monitored during and after 
the combination, and the dose of deferasirox adjusted if necessary. 
 
Cholestyramine significantly reduced the deferasirox exposure in a mechanistic study to determine 
the degree of enterohepatic recycling (see section 5.2). 
 
Interaction with midazolam and other agents metabolised by CYP3A4 
 
In a healthy volunteer study, the concomitant administration of deferasirox dispersible tablets and 
midazolam (a CYP3A4 probe substrate) resulted in a decrease of midazolam exposure by 17% (90% 



12 

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). 
 
Interaction with repaglinide and other agents metabolised by CYP2C8 
 
In a healthy volunteer study, the concomitant administration of deferasirox as a moderate 
CYP2C8 inhibitor (30 mg/kg daily, dispersible tablet formulation), with repaglinide, a CYP2C8 
substrate, given as a single dose of 0.5 mg, increased repaglinide AUC and Cmax 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 doses 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. 
 
Interaction with theophylline and other agents metabolised by CYP1A2 
 
In a healthy volunteer study, the concomitant administration of deferasirox as a CYP1A2 inhibitor 
(repeated dose of 30 mg/kg/day, dispersible tablet formulation) 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 Cmax was not affected, but an increase of theophylline Cmax is 
expected to occur with chronic dosing. Therefore, the concomitant use of deferasirox with 
theophylline is not recommended. If deferasirox and theophylline are used concomitantly, 
monitoring of theophylline concentration and theophylline dose reduction should be considered. An 
interaction between deferasirox 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. 
 
Other information 
 
The concomitant administration of deferasirox 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 deferasirox tablets with aluminium-containing antacid preparations. 
 
The concomitant administration of deferasirox 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 deferasirox with anticoagulants may also increase the risk of gastrointestinal 
haemorrhage. Close clinical monitoring is required when deferasirox is combined with these 
substances. 
 
Concomitant administration of deferasirox and busulfan resulted in an increase of busulfan exposure 
(AUC), but the mechanism of the interaction remains unclear. If possible, evaluation of the 
pharmacokinetics (AUC, clearance) of a busulfan test dose should be performed to allow dose 
adjustment. 
 
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 Deferasirox Accord is not used during pregnancy unless 
clearly necessary. 



13 

 
Deferasirox Accord may decrease the efficacy of hormonal contraceptives (see section 4.5). Women of 
childbearing potential are recommended to use additional or alternative non-hormonal methods of 
contraception when using Deferasirox Accord. 
 
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 Deferasirox Accord 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 
 
Deferasirox Accord has minor influence on the ability to drive and use machines. Patients 
experiencing the uncommon adverse reaction of dizziness should exercise caution when driving or 
operating machines (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequent reactions reported during chronic treatment in clinical studies conducted with 
deferasirox dispersible tablets in adult and paediatric patients include gastrointestinal disturbances 
(mainly nausea, vomiting, diarrhoea or abdominal pain) and skin rash. 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 studies dose-dependent increases in serum creatinine occurred in about 36% of 
patients, though most remained within the normal range. Decreases in mean creatinine clearance have 
been observed in both paediatric and adult patients with beta-thalassemia and iron overload during 
the first year of treatment, but there is evidence that this does not decrease further in subsequent 
years of treatment. Elevations of liver transaminases have been reported. Safety monitoring schedules 
for renal and liver parameters are recommended. Auditory (decreased hearing) and ocular (lens 
opacities) disturbances are uncommon, and yearly examinations are also recommended (see 
section 4.4). 
 
Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic 
epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) 
have been reported with the use of deferasirox (see section 4.4). 
 
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 5: Adverse reactions 
 
Blood and lymphatic system disorders 

Not known: Pancytopenia1, thrombocytopenia1, anaemia 



14 

aggravated1, neutropenia1 
Immune system disorders 

Not known: Hypersensitivity reactions (including anaphylactic reactions 
and angioedema)1 

Metabolism and nutrition disorders 
Not known: Metabolic acidosis1 

Psychiatric disorders 
Uncommon: Anxiety, sleep disorder 

Nervous system disorders 
Common: Headache 
Uncommon: Dizziness 

Eye disorders 
Uncommon: Cataract, maculopathy 
Rare: Optic neuritis 

Ear and labyrinth disorders 
Uncommon: Deafness 

Respiratory, thoracic and mediastinal disorders 
Uncommon: Laryngeal 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 perforation1, acute pancreatitis1 

Hepatobiliary disorders 
Common: Transaminases increased 
Uncommon: Hepatitis, cholelithiasis  
Not known: Hepatic failure1,2 

Skin and subcutaneous tissue disorders  
Common: Rash, pruritus  
Uncommon: Pigmentation disorder 
Rare: Drug reaction with eosinophilia and systemic symptoms (DRESS) 
Not known: Stevens-Johnson syndrome1, hypersensitivity vasculitis1, urticaria1, 

erythema multiforme1, alopecia1, toxic epidermal necrolysis 
(TEN)1 

Renal and urinary disorders 
Very common: Blood creatinine increased 
Common: Proteinuria 
Uncommon: Renal tubular disorder2 (acquired Fanconi syndrome), 

glycosuria  
Not known: Acute renal failure1,2, tubulointerstitial nephritis1, 

nephrolithiasis1, renal tubular necrosis1 
General disorders and administration site conditions 

Uncommon: Pyrexia, oedema, fatigue 
 

1 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. 

2 Severe forms associated with changes in consciousness in the context of hyperammonaemic 
encephalopathy have been reported. 

 
Description of selected adverse reactions 
 
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 



15 

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 
the deferasirox dispersible tablet formulation, 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 syndrome) or diarrhoea, or conditions 
where acid-base imbalance is a known complication (see section 4.4). Cases of serious acute 
pancreatitis were observed without documented underlying biliary conditions. As with other iron 
chelator treatment, high-frequency hearing loss and lenticular opacities (early cataracts) have been 
uncommonly observed in patients treated with deferasirox (see section 4.4). 
 
Creatinine clearance in transfusional iron overload 
 
In a retrospective meta-analysis of 2,102 adult and paediatric beta-thalassaemia patients with 
transfusional iron overload treated with deferasirox dispersible tablets in two randomised 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 250 patients who were 
followed for up to five years, no further decrease in mean creatinine clearance levels was observed. 
 
Clinical study in patients with non-transfusion-dependent thalassaemia syndromes 
 
In a 1-year study in patients with non-transfusion-dependent thalassaemia syndromes and iron 
overload (dispersible tablets at a dose of 10 mg/kg/day), diarrhoea (9.1%), rash (9.1%), and nausea 
(7.3%) were the most frequent study drug-related adverse reactions. Abnormal serum creatinine and 
creatinine clearance values were reported in 5.5% and 1.8% of patients, respectively. 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. 
 
Paediatric population 
 
In two clinical studies, growth and sexual development of paediatric patients treated with deferasirox 
for up to 5 years were not affected (see section 4.4). 
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 deferasirox. In post-marketing reports, a high proportion of cases of metabolic acidosis occurred in 
children in the context of Fanconi syndrome. 
 
Acute pancreatitis has been reported, particularly in children and adolescents. 
 
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. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in in Appendix V. 
 
4.9 Overdose 
 
Early signs of acute overdose are digestive effects such as abdominal pain, diarrhea, nausea and 
vomiting. Hepatic and renal disorders have been reported, including cases of liver enzyme and 
creatinine increased with recovery after treatment discontinuation. An erroneously administered single 
dose of 90 mg/kg led to Fanconi syndrome which resolved after treatment. 
 
There is no specific antidote for deferasirox. Standard procedures for management of overdose may be 
indicated as well as symptomatic treatment, as medically appropriate. 
 
 



16 

5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Iron chelating agents, 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, deferasirox at daily 
doses of 10, 20 and 40 mg/kg (dispersible tablet formulation) induced the mean net excretion of 0.119, 
0.329 and 0.445 mg Fe/kg body weight/day, respectively. 
 
Clinical efficacy and safety 
 
Clinical efficacy studies were conducted with deferasirox dispersible tablets. 
 
Deferasirox 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 with the deferasirox dispersible tablet formulation 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. Deferasirox 
induced similar responses in iron-overloaded patients with other anaemias. Daily doses of 10 mg/kg 
(dispersible tablet formulation) 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 deferasirox 10-
30 mg/kg/day (dispersible tablet formulation) 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 deferasirox 
dispersible tablets 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 deferasirox dispersible tablets (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 deferasirox dispersible tablets (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 deferasirox dispersible 
tablets. 
 



17 

It appeared from preclinical and clinical studies that deferasirox dispersible tablets could be as active 
as deferoxamine when used in a dose ratio of 2:1 (i.e. a dose of deferasirox dispersible tablets that is 
numerically half of the deferoxamine dose). For deferasirox film-coated tablets, a dose ratio of 3:1 can 
be considered (i.e. a dose of deferasirox film-coated tablets that is numerically one third of the 
deferoxamine dose). However, this dosing recommendation was not prospectively assessed in the 
clinical studies. 
 
In addition, in patients with liver iron concentration ≥7 mg Fe/g dw with various rare anaemias or 
sickle cell disease, deferasirox dispersible tablets 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 a 5-year observational study in which 267 children aged 2 to <6 years (at enrollment) with 
transfusional haemosiderosis received deferasirox, there were no clinically meaningful differences in 
the safety and tolerability profile of deferasirox in paediatric patients aged 2 to <6 years compared to 
the overall adult and older paediatric population, including increases in serum creatinine of >33% and 
above the upper limit of normal on ≥2 consecutive occasions (3.1%), and elevation of alanine 
aminotransferase (ALT) greater than 5 times the upper limit of normal (4.3%). Single events of 
increase in ALT and aspartate aminotransferase were reported in 20.0% and 8.3%, respectively, of the 
145 patients who completed the study. 
 
In a study to assess the safety of deferasirox film-coated and dispersible tablets, 173 adult and 
paediatric patients with transfusion dependent thalassaemia or myelodysplastic syndrome were treated 
for 24 weeks. A comparable safety profile for film-coated and dispersible tablets was observed. 
 
In patients with non-transfusion-dependent thalassaemia syndromes and iron overload, treatment with 
deferasirox dispersible tablets was assessed in a 1-year, randomised, double-blind, placebo-controlled 
study. The study compared the efficacy of two different deferasirox dispersible tablet 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, deferasirox dispersible tablets 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 deferasirox dispersible tablets (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 deferasirox dispersible tablets (starting dose 10 mg/kg/day) and increased by 115 µg/l in 
patients treated with placebo (p<0.001). 
 
5.2 Pharmacokinetic properties 
 
Deferasirox film-coated tablets demonstrate higher bioavailability compared to the deferasirox 
dispersible tablet formulation. After adjustment of the strength, the film-coated tablet formulation 
(360 mg strength) was equivalent to deferasirox dispersible tablets (500 mg strength) with respect to 
the mean area under the plasma concentration time curve (AUC) under fasting conditions. The Cmax 
was increased by 30% (90% CI: 20.3% - 40.0%); however a clinical exposure/response analysis 
revealed no evidence of clinically relevant effects of such an increase. 
 
Absorption 
 
Deferasirox (dispersible tablet formulation) is absorbed following oral administration with a median 
time to maximum plasma concentration (tmax) of about 1.5 to 4 hours. The absolute bioavailability 
(AUC) of deferasirox (dispersible tablet formulation) is about 70% compared to an intravenous dose. 
The absolute bioavailability of the film-coated tablet formulation has not been determined. 
Bioavailability of deferasirox film-coated tablets was 36% greater than that with dispersible tablets. 
 
A food-effect study involving administration of the film-coated tablets to healthy volunteers under 
fasting conditions and with a low-fat (fat content <10% of calories) or high-fat (fat content >50% of 



18 

calories) meal indicated that the AUC and Cmax were slightly decreased after a low-fat meal (by 
11% and 16%, respectively). After a high-fat meal, AUC and Cmax were increased (by 18% and 
29%, respectively). The increases in Cmax due to the change in formulation and due to the effect of a 
high-fat meal may be additive and therefore, it is recommended that the film-coated tablets should 
be taken either on an empty stomach or with a light meal. 
 
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 (t1/2) ranged from 8 to 16 hours. The transporters MRP2 and MXR (BCRP) are involved in the 
biliary excretion of deferasirox. 
 
Linearity / non-linearity 
 
The Cmax and AUC0-24h 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 
Elderly 
The pharmacokinetics of deferasirox have not been studied in elderly patients (aged 65 or older). 
 
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 dispersible tablets, 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 Cmax 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). 
 
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. 
 
Paediatric population 



19 

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. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans 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 negative (Ames test, chromosomal aberration test) while 
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 
 
Tablet core 
 
Cellulose, microcrystalline 
Croscarmellose sodium 
Low-substituted hydroxypropyl cellulose 
Povidone 
Poloxamer 
Lactose monohydrate 
Silica colloidal anhydrous 
Sodium stearyl fumarate 
Hydrogenated castor oil 
 
Tablet coat 
 
Hypromellose (E464) 
Propylene glycol (E1520) 
Talc (E553b) 
Iron oxide yellow (E172) 
Titanium dioxide (E171) 
 
6.2 Incompatibilities 
 
Not applicable.  
 
6.3 Shelf life 
 
2 years. 
 



20 

6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
PVC/PE/PVdC-Aluminium blisters. 
 
Unit packs containing 28 x 1, 30 x 1, 56 x 1 or 90 x 1 film-coated tablet. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U. 
World Trade Center, Moll de Barcelona s/n, 
Edifici Est, 6a Planta,  
Barcelona, 08039 
Spain 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Deferasirox Accord 90 mg film-coated tablets  
 
EU/1/19/1412/001 
EU/1/19/1412/002 
EU/1/19/1412/003 
EU/1/19/1412/004 
 
Deferasirox Accord 180 mg film-coated tablets  
 
EU/1/19/1412/005 
EU/1/19/1412/006 
EU/1/19/1412/007 
EU/1/19/1412/008 
 
Deferasirox Accord 360 mg film-coated tablets  
 
EU/1/19/1412/009 
EU/1/19/1412/010 
EU/1/19/1412/011 
EU/1/19/1412/012 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 09th January 2020 
 
 
10. DATE OF REVISION OF THE TEXT 
 



21 

 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu



22 

  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A.  MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
B.  CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D.  CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 



23 

 
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Accord Healthcare Polska Sp.z.o.o. 
Ul. Lutomierska 50,  
96-200, Pabianice, Poland 
 
Pharmadox Healthcare Limited  
KW20A Kordin Industrial Park,  
Paola PLA 3000, Malta 
 
LABORATORI FUNDACIÓ DAU 
C/ C, 12-14 Pol. Ind. Zona Franca,  
Barcelona, 08040 Barcelona, Spain 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic safety update report (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
 Additional risk minimisation measures 
 
The MAH must inform the European Medicines Agency and the CHMP of the results of the 
surveillance programme in each Member State. 
 
As well as the requirements in the legislation, the following serious ADRs should be forwarded on an 
expedited basis to the appropriate competent authority as well as summarised in the periodic safety 
update reports: 



24 

o Increase in hepatic enzymes >10x ULN 
o Serious rise in creatinine 
o Results of renal biopsies, if available 
o Cataracts 
o Hearing loss 
o Gallstones 

 
Prior to launch of Deferasirox Accord in each Member State the Marketing Authorisation Holder 
(MAH) must agree about the content and format of the educational programme, including 
communication media, distribution modalities, and any other aspects of the programme, with the 
National Competent Authority. 
 
The educational programme is aimed to inform healthcare professionals and patients to minimise 
the risks of: 
 Non-compliance of the posology and biological monitoring 
 Medication errors [due to switching between formulations available on the market by 

different MAHs (dispersible tablets and film-coated tablets/granules)] 
 
The MAH shall ensure that, at launch, in each Member State where Deferasirox Accord is marketed, 
all healthcare professionals and patients who are expected to prescribe, dispense and use Deferasirox 
Accord are provided with the following educational package for all available formulations (e.g. 
dispersible tablets, film-coated tablets and granules) for all indications: 
 Physician educational material 
 Patient information pack 
 
Additional periodic distributions after launch should be performed, notably after substantial safety 
modifications of the product information justifying educational material updates. 
 
The physician educational material should contain: 
 The Summary of Product Characteristics 
 Guide for healthcare professionals 
 
The Guide for healthcare professionals shall contain the following key elements: 
 Description of available deferasirox formulations on the market (e.g. dispersible tablets, film-

coated tablets and granules) 
◦ Different posology regimen 
◦ Different conditions of administration 
◦ Dose conversion table when switching from one formulation to another 

 The recommended doses and the rules for starting treatment 
 The need to monitor serum ferritin monthly 
 
 That deferasirox causes rises in serum creatinine in some patients 

◦ The need to monitor serum creatinine 
▪ On two occasions prior to initiation of treatment 
▪ Every week during the first month of initiation of treatment or after therapy 

modification 
▪ Monthly thereafter 

 
◦ The need to reduce by 10 mg/kg the dose if serum creatinine rises: 

▪ Adults: >33% above baseline and creatinine clearance <LLN (90 ml/min) 
▪ Paediatrics: either >ULN or creatinine clearance falls to <LLN at two 

consecutive visits. 
 

◦ The need to interrupt treatment after a dose reduction if serum creatinine rises: 
▪ Adults and Paediatrics: remain >33% above baseline or creatinine clearance 

<LLN (90 ml/min) 
 



25 

◦ The need to consider renal biopsy: 
▪ When serum creatinine is elevated and if another abnormality has been 

detected (e.g. proteinuria, signs of Fanconi syndrome). 
 
 The importance of measuring creatinine clearance 
 Brief overview of methods of measuring creatinine clearance 
 
 That rises in serum transaminases may occur in patients treated with Deferasirox Accord 

◦ The need for liver function tests prior to prescription, then at monthly intervals or 
more often if clinically indicated 

◦ Not to prescribe to patients with pre-existing severe hepatic disease 
◦ The need to interrupt treatment if persistent and progressive increase in liver enzyme 

were noted. 
 The need for annual auditory and ophthalmic testing 
 
 The need for a guidance table highlighting pre-treatment measurements of serum creatinine, 

creatinine clearance, proteinuria, hepatic enzymes, ferritin, such as: 
Before initiating treatment 
Serum creatinine at Day – X Value 1 
Serum creatinine at Day – Y Value 2 
X and Y are the days (to be determined) when pre-treatment measurements should be 
performed. 

 
 A warning on the risk of overchelation and on the necessity of close monitoring of serum 

ferritin levels and renal and hepatic function. 
 
 The rules for treatment dose adjustments and interruption when target serum ferritin +/− 

liver iron concentration are reached. 
 
 Recommendations for treatment of non-transfusion-dependent thalassaemia (NTDT) 

syndromes: 
◦ Information that only one course of treatment is proposed for NTDT patients 
◦ A warning on the necessity of closer monitoring of liver iron concentration and 

serum ferritin in the paediatric population 
◦ A warning on the currently unknown safety consequences of long-term treatment in 

the paediatric population 
 
The patient information pack should contain: 
 Patient information leaflet 
 Patient guide 
 
Patient guide should contain the following key elements: 

◦ Information on the need for regular monitoring, and when it should be carried out, 
of serum creatinine, creatinine clearance, proteinuria, hepatic enzymes, ferritin 

◦ Information that renal biopsy may be considered if significant renal abnormalities occur 
◦ Availability of several oral formulations (e.g. dispersible tablets, film-coated tablets 

and granules) and the main differences associated with these formulations (i.e., 
different posology regimen, different conditions of administration notably with food) 



26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



27 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



28 

  
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Deferasirox Accord 90 mg film-coated tablets 
deferasirox 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 90 mg deferasirox. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose and castor oil. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablets 
 
28 x 1 film-coated tablet 
30 x 1 film-coated tablet 
56 x 1 film-coated tablet 
90 x 1 film-coated tablet 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



29 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U. 
World Trade Center, Moll de Barcelona s/n, 
Edifici Est, 6a Planta, 
Barcelona, 08039 
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/19/1412/001 
EU/1/19/1412/002 
EU/1/19/1412/003 
EU/1/19/1412/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Deferasirox Accord 90 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



30 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Blister label 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Deferasirox Accord 90 mg film-coated tablets 
deferasirox 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Accord 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



31 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Deferasirox Accord 180 mg film-coated tablets 
deferasirox 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 180 mg deferasirox. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose and castor oil. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablets 
 
28 x 1 film-coated tablet 
30 x 1 film-coated tablet 
56 x 1 film-coated tablet 
90 x 1 film-coated tablet 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



32 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U. 
World Trade Center, Moll de Barcelona s/n, 
Edifici Est, 6a Planta, 
Barcelona, 08039 
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/19/1412/005 
EU/1/19/1412/006 
EU/1/19/1412/007 
EU/1/19/1412/008 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Deferasirox Accord 180 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



33 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Blister label  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Deferasirox Accord 180 mg film-coated tablets 
deferasirox 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Accord 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



34 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Outer carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Deferasirox Accord 360 mg film-coated tablets 
deferasirox 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 360 mg deferasirox. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains lactose and castor oil. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Film-coated tablets 
28 x 1 film-coated tablet 
30 x 1 film-coated tablet 
56 x 1 film-coated tablet 
90 x 1 film-coated tablet 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



35 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Accord Healthcare S.L.U. 
World Trade Center, Moll de Barcelona s/n, 
Edifici Est, 6a Planta, 
Barcelona, 08039 
Spain 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/19/1412/009 
EU/1/19/1412/010 
EU/1/19/1412/011 
EU/1/19/1412/012 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Deferasirox Accord 360 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



36 

 
 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
Blister label 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Deferasirox Accord 360 mg film-coated tablets 
deferasirox 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Accord 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



37 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



38 

Package leaflet: Information for the patient 
 

Deferasirox Accord 90 mg film-coated tablets  
Deferasirox Accord 180 mg film-coated tablets  
Deferasirox Accord 360 mg film-coated tablets  

deferasirox 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
 Keep this leaflet. You may need to read it again.  
 If you have any further questions, ask your doctor or pharmacist. 
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  
 If you get any side effects, talk to your doctor or pharmacist.This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Deferasirox Accord is and what it is used for  
2. What you need to know before you take Deferasirox Accord  
3. How to take Deferasirox Accord 
4. Possible side effects  
5. How to store Deferasirox Accord 
6. Contents of the pack and other information 
 
 
1. What Deferasirox Accord is and what it is used for 
 
What Deferasirox Accord is 
Deferasirox Accord contains an active substance called deferasirox. It is an iron chelator which is a 
medicine used to remove the excess iron from the body (also called iron overload). It traps and 
removes excess iron which is then excreted mainly in the stools. 
 
What Deferasirox Accord is used for 
Repeated blood transfusions may be necessary in patients with various types of anaemia (for example 
thalassaemia, sickle cell disease or myelodysplastic syndromes (MDS)). However, repeated blood 
transfusions can cause a build-up of excess iron. This is because blood contains iron and your body 
does not have a natural way to remove the excess iron you get with your blood transfusions. In patients 
with non-transfusion-dependent thalassaemia syndromes, iron overload may also 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. 
 
Deferasirox Accord is used to treat chronic iron overload caused by frequent blood transfusions in 
patients with beta thalassaemia major aged 6 years and older. 
 
Deferasirox Accord is also used to treat chronic iron overload when deferoxamine therapy is 
contraindicated or inadequate in patients with beta thalassaemia major with iron overload caused by 
infrequent blood transfusions, in patients with other types of anaemias, and in children aged 2 to 
5 years. 
 
Deferasirox Accord is also used when deferoxamine therapy is contraindicated or inadequate to treat 
patients aged 10 years or older who have iron overload associated with their thalassaemia syndromes, 
but who are not transfusion dependent. 
 
 
2. What you need to know before you take Deferasirox Accord 



39 

 
Do not take Deferasirox Accord 
• if you are allergic to deferasirox or any of the other ingredients of this medicine (listed in 

section 6). If this applies to you, tell your doctor before taking Deferasirox Accord. If you 
think you may be allergic, ask your doctor for advice. 

• if you have moderate or severe kidney disease. 
• if you are currently taking any other iron chelator medicines. 
 
Deferasirox Accord is not recommended 
• if you are at an advanced stage of myelodysplastic syndrome (MDS; decreased production of 

blood cells by the bone marrow) or have advanced cancer. 
 

Warnings and precautions  
Talk to your doctor or pharmacist before taking Deferasirox Accord: 
• if you have a kidney or liver problem. 
• if you have a cardiac problem due to iron overload. 
• if you notice a marked decrease in your urine output (sign of kidney problem). 
• if 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 “Possible side effects”). 
• if you experience a combination of any of the following symptoms: rash, red skin, blistering of 

the lips, eyes or mouth, skin peeling, high fever, flu-like symptoms, enlarged lymph nodes 
(signs of severe skin reaction, see also section 4 “Possible side effects”). 

• if 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). 

• if you experience difficulty thinking, remembering information, or solving problems, being less 
alert or aware or feeling very sleepy with low energy (signs of a high level of ammonia in your 
blood, which may be associated with liver or renal problems, see also section 4 “Possible side 
effects”). 

• if you vomit blood and/or have black stools. 
• if you experience frequent abdominal pain, particularly after eating or taking Deferasirox 

Accord. 
• if you experience frequent heartburn. 
• if you have a low level of platelets or white blood cells in your blood test. 
• if you have blurred vision 
• if you have diarrhoea or vomiting. 
• If any of these apply to you, tell your doctor straight away. 
 
Monitoring your Deferasirox Accord treatment 
You will have regular blood and urine tests during treatment. These will monitor the amount of iron in 
your body (blood level of ferritin) to see how well Deferasirox Accord is working. The tests will also 
monitor your kidney function (blood level of creatinine, presence of protein in the urine) and liver 
function (blood level of transaminases). Your doctor may require you to undergo a kidney biopsy, if 
he/she suspects significant kidney damage. 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 Deferasirox Accord most suitable for you and will also use these tests to 
decide when you should stop taking Deferasirox Accord. 
 
Your eyesight and hearing will be tested each year during treatment as a precautionary measure. 
 
Other medicines and Deferasirox Accord 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  
This includes in particular: 
• other iron chelators, which must not be taken with Deferasirox Accord, 
• antacids (medicines used to treat heartburn) containing aluminium, which should not be taken at 

the same time of day as Deferasirox Accord, 



40 

• 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 (used for heart problems and migraines), 
• 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). 
• busulfan (used as a treatment prior to transplantation in order to destroy the original bone 

marrow before the transplant). 
 
Additional tests may be required to monitor the blood levels of some of these medicines. 
 
Older people (age 65 years and over) 
Deferasirox Accord can be used by people aged 65 years and over 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 side effects that may require a dose adjustment. 
 
Children and adolescents 
Deferasirox Accord can be used in children and adolescents receiving regular blood transfusions aged 
2 years and over and in children and adolescents not receiving regular blood transfusions aged 
10 years and over. As the patient grows the doctor will adjust the dose. 
 
Deferasirox Accord is not recommended for children aged under 2 years. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
 
Deferasirox Accord is not recommended during pregnancy unless clearly necessary. 
 
If you are currently using an oral contraceptive or using a patch contraceptive to prevent pregnancy, 
you should use an additional or different type of contraception (e.g. condom), as Deferasirox Accord 
may reduce the effectiveness of oral and patch contraceptives. 
 
Breast-feeding is not recommended during treatment with Deferasirox Accord. 
 
Driving and using machines 
If you feel dizzy after taking Deferasirox Accord, do not drive or operate any tools or machines until 
you are feeling normal again. 
 
Deferasirox Accord contains lactose (a type of sugar) 
If you have been told by your doctor that you have an intolerance to some sugars contact your doctor 
before taking this medicinal product. 
 
Deferasirox Accord contains sodium 



41 

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 
‘sodium-free’. 
 
Deferasirox Accord contains castor oil 
This medicinal product may cause stomach upset and diarrhea. 
 
 
3. How to take Deferasirox Accord 
 
Treatment with Deferasirox Accord will be overseen by a doctor who is experienced in the treatment 
of iron overload caused by blood transfusions. 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 
How much Deferasirox Accord to take 
The dose of Deferasirox Accord 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 for Deferasirox Accord film-coated tablets at the start of the treatment for 

patients receiving regular blood transfusions is 14 mg per kilogram body weight. A higher or 
lower starting dose may be recommended by your doctor based on your individual treatment 
needs. 

• The usual daily dose for Deferasirox Accord film-coated tablets at the start of the treatment for 
patients not receiving regular blood transfusions is 7 mg per kilogram body weight. 

• Depending on how you respond to treatment, your doctor may later adjust your treatment to a 
higher or lower dose. 

• The maximum recommended daily dose for Deferasirox Accord film-coated tablets is: 
- 28 mg per kilogram body weight for patients receiving regular blood transfusions, 
- 14 mg per kilogram body weight for adult patients not receiving regular blood 

transfusions, 
- 7 mg per kilogram body weight for children and adolescents not receiving regular 

blood transfusions. 
 
Deferasirox also comes as “dispersible” tablets. If you are switching from the dispersible tablets to 
these film-coated tablets, you will need an adjustment of the dose. 
 
When to take Deferasirox Accord 
• Take Deferasirox Accord once a day, every day, at about the same time each day with some 

water. 
• Take Deferasirox Accord film-coated tablets either on an empty stomach or with a light meal. 
Taking Deferasirox Accord at the same time each day will also help you remember when to take your 
tablets. 
 
For patients who are unable to swallow whole tablets, Deferasirox Accord film-coated tablets may be 
crushed and taken by sprinkling the full dose onto soft food such as yogurt or apple sauce (pureed 
apple). The food should be immediately and completely consumed. Do not store it for future use. 
 
How long to take Deferasirox Accord 
Continue taking Deferasirox Accord every day for as long as your doctor tells you. This is a long-term 
treatment, possibly lasting for months or years. Your doctor will regularly monitor your condition to 
check that the treatment is having the desired effect (see also section 2: “Monitoring your Deferasirox 
Accord treatment”). 
 
If you have questions about how long to take Deferasirox Accord, talk to your doctor. 
 
If you take more Deferasirox Accord than you should 



42 

If you have taken too much Deferasirox Accord, or if someone else accidentally takes your tablets, 
contact your doctor or hospital for advice straight away. Show the doctor the pack of tablets. Urgent 
medical treatment may be necessary. You may experience effects such as abdominal pain, diarrhoea, 
nausea and vomiting and kidney or liver problems that can be serious. 
 
If you forget to take Deferasirox Accord 
If you miss a dose, take it as soon as you remember on that day. Take your next dose as scheduled. Do 
not take a double dose on the next day to make up for the forgotten tablet(s). 
 
If you stop taking Deferasirox Accord 
Do not stop taking Deferasirox Accord unless your doctor tells you to. If you stop taking it, the excess 
iron will no longer be removed from your body (see also above section “How long to take Deferasirox 
Accord”). 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets 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 (may affect up to 1 in 100 people) or rare (may affect up to 1 in 
1,000 people). 
• If you get a severe rash, or difficulty breathing and dizziness or swelling mainly of the face and 

throat (signs of severe allergic reaction), 
• If you experience a combination of any of the following symptoms: rash, red skin, blistering of 

the lips, eyes or mouth, skin peeling, high fever, flu-like symptoms, enlarged lymph nodes, 
(signs of severe skin reactions), 

• If you notice a marked decrease in your urine output (sign of kidney problem), 
• If 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), 
• If you experience difficulty thinking, remembering information, or solving problems, being less 

alert or aware or feeling very sleepy with low energy (signs of a high level of ammonia in your 
blood, which may be associated with liver or renal problems and lead to a change in your brain 
function), 

• If you vomit blood and/or have black stools, 
• If you experience frequent abdominal pain, particularly after eating or taking Deferasirox 

Accord, 
• If you experience frequent heartburn, 
• If you experience partial loss of vision, 
• If you experience severe upper stomach pain (pancreatitis), 
stop taking this medicine and tell your doctor straight away. 
 
Some side effects could become serious. 
These side effects are uncommon. 
• If you get blurred or cloudy eyesight, 
• If you get reduced hearing, 
tell your doctor as soon as possible. 
 
Other side effects 
Very common (may affect more than 1 in 10 people) 
• Disturbance in kidney function tests. 
 
Common (may affect up to 1 in 10 people) 
• Gastrointestinal disorders, such as nausea, vomiting, diarrhoea, pain in the abdomen, bloating, 



43 

constipation, indigestion 
• Rash 
• Headache 
• Disturbance in liver function tests 
• Itching 
• Disturbance in urine test (protein in the urine)  
If any of these affects you severely, tell your doctor. 
 
Uncommon (may affect up to 1 in 100 people) 
• Dizziness 
• Fever 
• Sore throat 
• Swelling of arms or legs 
• Change in the colour of the skin 
• Anxiety 
• Sleep disorder 
• Tiredness 
If any of these affects you severely, tell your doctor. 
 
Frequency not known (cannot be estimated from the available data). 
• A decrease in the number of 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 
• Tear in stomach or intestine wall that can be painful and cause nausea 
• Severe upper stomach pain (pancreatitis) 
• Abnormal level of acid in blood 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Deferasirox Accord 
 
• Keep this medicine out of the sight and reach of children. 
• Do not use this medicine after the expiry date which is stated on the blister and the carton after 

EXP. The expiry date refers to the last day of that month. 
• Do not use any pack that is damaged or shows signs of tampering. 
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how 

to throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Deferasirox Accord contains: 
The active substance is deferasirox. 
Each film-coated tablet contains 90 mg deferasirox. 
Each film-coated tablet contains 180 mg deferasirox. 
Each film-coated tablet contains 360 mg deferasirox.  
 
The other ingredients are: 



44 

Tablet core: cellulose, microcrystalline, croscarmellose sodium, low-substituted hydroxypropyl 
cellulose, povidone, poloxamer, lactose monohydrate, silica colloidal anhydrous, sodium stearyl 
fumarate, hydrogenated castor oil (see section 2). 
 
Tablet coat: hypromellose (E464), propylene glycol (E1520), talc (E553b), iron oxide yellow (E172), 
titanium dioxide (E171). 
 
What Deferasirox Accord looks like and contents of the pack: 
Deferasirox Accord 90 mg are yellow colored, film coated oval, biconvex tablets with beveled edges 
debossed with ‘D’ on one side and ‘90’ on another side. 
 
Deferasirox Accord 180 mg are yellow colored, film coated oval, biconvex tablets with beveled edges 
debossed with ‘D’ on one side and ‘180’ on another side. 
 
Deferasirox Accord 360 mg are yellow colored, film coated oval, biconvex tablets with beveled edges 
debossed with ‘D’ on one side and ‘360’ on another side. 
 
Deferasirox Accord film-coated tablets are available in PVC/PE/PVdC-Aluminium blisters, unit packs 
containing 28 x 1, 30 x 1, 56 x 1 or 90 x 1 film-coated tablet. 
 
Marketing Authorisation Holder 
Accord Healthcare S.L.U. 
World Trade Center, Moll de Barcelona s/n, 
Edifici Est, 6a Planta,  
Barcelona, 08039 
Spain 
 
Manufacturer 
Accord Healthcare Polska Sp.z.o.o. 
Ul. Lutomierska 50,  
96-200, Pabianice, Poland 
 
Pharmadox Healthcare Limited  
KW20A Kordin Industrial Park,  
Paola PLA 3000, Malta 
 
LABORATORI FUNDACIÓ DAU 
C/ C, 12-14 Pol. Ind. Zona Franca,  
Barcelona, 08040 Barcelona, Spain 
 
This leaflet was last revised in {MM/YYYY} 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET