Deferasirox

Registered South African indications:

• Chronic iron overload 

Contraindications

South African manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients 
• Pregnancy 
• Breastfeeding 
• CrCl<60ml/min
• eGFR<40ml/min/1.73m² (fct)
• Severe hepatic impairment
• High risk myelodysplastic syndrome (MDS)
• Haematological and non-haematological malignancies with limited expected survival (<1 year) who are not expected to benefit from chelation therapy due to rapid progression of their disease
• Platelet counts<50x10⁹/l (fct)
• Poor performance status (fct)
• Advanced malignancies (fct)
• Coadministation with repaglinide 
• Coadministration with other iron chelator therapies (fct)

International manufacturer recommendations 

• Hypersensitivity to the active ingredient or any of its excipients 
• eGFR<40ml/min/1.73m² 
• Coadministration with other iron chelator therapies

Cautions

South African manufacturer recommendations

• eGFR>40ml/min/1.73m² 
• Mild to moderate hepatic impairment
• Elderly
• Children
  - Decreases in eGFR
  - Beta-thalassaemia and serum ferritin <1,500 microgram/l 
• Significant comorbidities including liver cirrhosis and multi-organ failure
• Pre-existing renal conditions
• Pre-existing haematological disorders associated with bone marrow failure 
• Previous severe cutaneous adverse reactions (SCARs) experience
• Previous hypersensitivity reaction experience
• Unexplained anaemia or other cytopenias
• High doses given to patients with low iron burden or with serum ferritin levels that are slightly elevated
• Continued administration in the 14-28mg/kg/day range when the body iron burden is approaching or within the normal range
• Coadministration with aluminium-containing antacids (fct)
• Coadministration with agents with ulcerogenic potential e.g. non-steroidal anti-inflammatory drugs, corticosteroids, or oral bisphosphonates
• Coadministration with anticoagulants
• Coadministration with medicinal agents that depress renal function
• Galactose intolerance 
• Lapp lactase deficiency 
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

International manufacturer recommendations 

• Pregnancy
• Breastfeeding
• eGFR 40-59ml/min/1.73m² 
• Hepatic impairment
• Elderly
• Children
  - Acute illness 
• Pre-existing renal conditions (e.g. Fanconi syndrome)
• Pre-existing chronic hepatic conditions (including cirrhosis and hepatitis C) and multi-organ failure
• 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)
• High doses and when serum ferritin levels are close to the target range
• Short life expectancy e.g. high risk myelodysplastic syndrome
• Haematological malignancies
• Previous severe cutaneous adverse reactions (SCARs) experience
• Previous hypersensitivity reaction experience
• Pre-existing haematological disorders associated with bone marrow failure 
• Retreatment of patients who reaccumulate iron after having achieved a satisfactory body iron level
• Platelet counts <50,000/mm³ 
• Unexplained cytopenia
• Coadministration with medicinal agents that depress renal function
• Coadministration with aluminium-containing antacids 
• Coadministration with agents with ulcerogenic potential e.g. non-steroidal anti-inflammatory drugs, corticosteroids, or oral bisphosphonates
• Coadministration with anticoagulants
• May impair ability to drive and operate machinery 

Forms avail. in SA and covered in this monograph: dsp, fct

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Treatment should be initiated and maintained by a medical practitioner experienced in the treatment of chronic iron overload

Chronic iron overload
- Due to blood transfusions (transfusional haemosiderosis) 

• Oral (dsp): Initial: 10-30mg/kg, dly; Titrate up or down by 5-10mg/kg at intervals of 3-6 months; Max: 40mg/kg/24hrs (See table)
• Oral (fct): Initial: 7-21mg/kg, dly (See table); Titrate up or down by 3.5-7mg/kg at intervals of 3-6 months; Max: 28mg/kg/24hrs (See table)

	Dispersible tablets starting dose/day	Film-coated tablets starting dose/day
After >20 units (about 100ml/kg of packed red blood cells (PRBC)) OR serum ferritin >1000ug/l	20mg/kg	14mg/kg
>14ml/kg/month of PRBC / >4 units/month	30mg/kg	21mg/kg
<7ml/kg/month of PRBC / <2 units/month	10mg/kg	7mg/kg
Patients well managed on deferoxamine
	Half of deferoxamine dose	One third of deferoxamine dose
Dose adjustments (every 3-6 months)
Increase dose (if serum ferritin >2500μg/l)	Increase by 5-10mg/kg Up to 28mg/kg	Increase by 3.5-7mg/kg Up to 28mg/kg
Decrease dose (if serum ferritin <2500μg/l)	Decrease by 5-10mg/kg In patients treated with doses >30mg/kg	Decrease by 3.5-7mg/kg In patients treated with doses >21mg/kg
Maximum dose	40mg/kg	28mg/kg

---

The starting dose is determined by the frequency of blood transfusions. It is recommended that therapy be started after the transfusion of approximately 20 units (about 100ml/kg) of packed red blood cells or when there is evidence from clinical monitoring that chronic iron overload is present (e.g. serum ferritin >1000microgram/l) 

---

The decision to remove accumulated iron should be individualised based on anticipated clinical benefit and risks of chelation therapy

---

Doses (in mg/kg) must be calculated and rounded to the nearest whole tablet size

---

Serum ferritin target range: 500-1000microgram/l . If serum ferritin falls consistently below 500microgram/l, an interruption of treatment should be considered

---

Film coated tablets can be taken on an empty stomach or with a light meal. May be crushed and mixed with soft foods (e.g. yogurt or apple sauce (pureed apple))

---

Dispersible tablets should be taken once daily on an empty stomach at least 30min before food, and must not be chewed or swallowed whole. Disperse by stirring in a glass of 100-200ml water or juice (apple or orange) until a fine suspension is obtained. Dispersion in carbonated drinks or milk is not recommended

---

If 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

---

Chronic iron overload
- Non-transfusion-dependent thalassemia syndrome

• Oral (dsp): Initial: 10mg/kg, dly; Titrate up or down by 5-10mg/kg at intervals of 3-6 months; Max: 20mg/kg/24hrs 
• Oral (fct): Initial: 7mg/kg, dly; Titrate up or down by 3.5-7mg/kg at intervals of 3-6 months; Max: 14mg/kg/24hrs

	Dispersible tablets dose/day	Film-coated tablets dose/day
Liver iron concentration (LIC) ≥5mg Fe/g dw* OR serum ferritin >800μg/l	Starting dose: 10mg/kg	Starting dose: 7mg/kg
Dose adjustments (every 3-6 months)
Increase dose (LIC≥7mg Fe/g dw OR serum ferritin >2000μg/l)	Increase by 5-10mg/kg	Increase by 3.5-7mg/kg
Decrease dose (LIC<7mg Fe/g dw OR serum ferritin <2000μg/l)	Decrease by 5-10mg/kg	Decrease by 3.5-7mg/kg
Maximum dose	20mg/kg/day	14mg/kg

*dw - dry weight

---

Target iron level is liver iron concentration (LIC) <3mg Fe/g dry weight (dw) or serum ferritin <300microgram/l, and then treatment may be interrupted

---

Serum ferritin to be monitored every month to assess the patients’s response to therapy and to minimise the risk of overchelation 

---

Doses (in mg/kg) must be calculated and rounded to the nearest whole tablet size

---

Therapy should only be initiated when there is evidence of iron overload - LIC ≥5mg Fe/g dw or serum ferritin consistently >800microgram/l

---

If the baseline LIC is greater than 15mg Fe/g dw, consider increasing the dose to a maximum of 14mg/kg/day after 4 weeks (dispersible tablets)

---

In patients in whom LIC was not assessed and serum ferritin is ≤2,000microgram/l dosing should not exceed 10mg/kg (dispersible tablets) or 7mg/kg (film coated tablets) 

---

Film coated tablets can be taken on an empty stomach or with a light meal. May be crushed and mixed with soft foods (e.g. yogurt or apple sauce (pureed apple))

---

Dispersible tablets should be taken once daily on an empty stomach at least 30min before food, and must not be chewed or swallowed whole. Disperse by stirring in a glass of 100-200ml water or juice (apple or orange) until a fine suspension is obtained. Dispersion in carbonated drinks or milk is not recommended

---

If 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

---

International manufacturer recommendations

Treatment should be initiated and maintained by a medical practitioner experienced in the treatment of chronic iron overload

Chronic iron overload
- Due to blood transfusions (≥7ml/kg/month of packed red blood cells) in those with beta thalassaemia major
- Due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in those with beta thalassaemia major with iron overload due to infrequent blood transfusions (<7ml/kg/month of packed red blood cells)
- Due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in patients with other anaemias

• Oral (dsp): Initial: 10-30mg/kg, dly; Titrate up or down by 5-10mg/kg at intervals of 3-6 months; Max: 40mg/kg/24hrs (See table)
• Oral (fct): Initial: 7-21mg/kg, dly (See table); Titrate up or down by 3.5-7mg/kg at intervals of 3-6 months; Max: 28mg/kg/24hrs (See table)

	Dispersible tablets starting dose/day	Film-coated tablets starting dose/day
After >20 units (about 100ml/kg of packed red blood cells (PRBC)) OR serum ferritin >1000ug/l	20mg/kg	14mg/kg
>14ml/kg/month of PRBC / >4 units/month	30mg/kg	21mg/kg
<7ml/kg/month of PRBC / <2 units/month	10mg/kg	7mg/kg
Patients well managed on deferoxamine
	Half of deferoxamine dose	One third of deferoxamine dose
Dose adjustments (every 3-6 months)
Increase dose (if serum ferritin >2500μg/l)	Increase by 5-10mg/kg	Increase by 3.5-7mg/kg
Decrease dose (if serum ferritin <2500μg/l)	Decrease by 5-10mg/kg In patients treated with doses >30mg/kg	Decrease by 3.5-7mg/kg In patients treated with doses >21mg/kg
Maximum dose	40mg/kg	28mg/kg

---

 It is recommended that therapy be started after the transfusion of approximately 20 units (about 100ml/kg) of packed red blood cells or when there is evidence from clinical monitoring that chronic iron overload is present (e.g. serum ferritin >1000microgram/l) 

---

Serum ferritin to be monitored every month to assess the patients’s response to therapy and to minimize the risk of overchelation 

---

Doses (in mg/kg) must be calculated and rounded to the nearest whole tablet size

---

Serum ferritin target range: 500-1000microgram/l . If serum ferritin falls consistently below 500microgram/l, an interruption of treatment should be considered

---

Film coated tablets can be taken on an empty stomach or with a light meal. May be crushed and mixed with soft foods (e.g. yogurt or apple sauce (pureed apple))

---

If 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

---

Chronic iron overload
- Requiring chelation therapy when deferoxamine therapy is contraindicated or inadequate in patients with non-transfusion-dependent thalassaemia syndromes

• Oral (dsp): Initial: 10mg/kg, dly; Titrate up or down by 5-10mg/kg at intervals of 3-6 months; Max: 20mg/kg/24hrs
• Oral (fct): Initial: 7mg/kg, dly; Titrate up or down by 3.5-7mg/kg at intervals of 3-6 months; Max: 14mg/kg/24hrs

	Dispersible tablets dose/day	Film-coated tablets dose/day
Liver iron concentration (LIC) ≥5mg Fe/g dw OR serum ferritin >800ug/l	Starting dose: 10mg/kg	Starting dose: 7mg/kg
Dose adjustments (every 3-6 months)
Increase dose (LIC≥7mg Fe/g dw OR serum ferritin >2000ug/l)	Increase by 5-10mg/kg	Increase by 3.5-7mg/kg
Decrease dose (LIC<7mg Fe/g dw OR serum ferritin <2000ug/l)	Decrease by 5-10mg/kg	Decrease by 3.5-7mg/kg
Maximum dose	20mg/kg/day	14mg/kg

*dw - dry weight

---

Target iron level is liver iron concentration (LIC) <3mg Fe/g dry weight (dw) or serum ferritin <300microgram/l, and then treatment may be interrupted

---

Serum ferritin to be monitored every month to assess the patients’s response to therapy and to minimize the risk of overchelation 

---

Doses (in mg/kg) must be calculated and rounded to the nearest whole tablet size

---

Therapy should only be initiated when there is evidence of iron overload - LIC≥5mg Fe/g dw or serum ferritin consistently >800microgram/l

---

In patients in whom LIC was not assessed and serum ferritin is ≤2,000microgram/l dosing should not exceed 10mg/kg (dispersible tablets) or 7mg/kg (film coated tablets) 

---

Film coated tablets can be taken on an empty stomach or with a light meal. May be crushed and mixed with soft foods (e.g. yogurt or apple sauce (pureed apple))

---

If 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

Paed. forms avail. in SA and covered in this monograph: dsp, fct

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Chronic iron overload
- Due to blood transfusions (transfusional haemosiderosis)

Younger than 2 years

• Not established for use

Between 2-17 years 

• See adult dosage 

- Non-transfusion-dependent thalassemia syndromes

Younger than 10 years

• No information available

Older than 10 years 

• See adult dosage

---

Changes in weight of paediatric patients over time must be taken into account when calculating the dose

---

International manufacturer recommendations

Chronic iron overload
- Due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in patients with beta thalassaemia major with iron overload due to frequent blood transfusions (≥7ml/kg/month of PRBC)

Younger than 2 years

• Not established for use

Between 2-5 years

• See adult dosage

Older than 5 years

• No information available

- Due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in patients with beta thalassaemia major with iron overload due to infrequent blood transfusions (<7ml/kg/month of PRBC)
- Due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in patients with other anaemias

Younger than 2 years

• Not established for use

Between 2-17 years

• See adult dosage 
  Since dosing is individually adjusted according to response the lower exposure is not expected to have clinical consequences

---

The dosing recommendations for paediatric patients aged 2-17 years with transfusional iron overload are the same as for adult patients. 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. 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 2-5 years, exposure is lower than in adults. 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

---

- Due to blood transfusions (≥7ml/kg/month of packed red blood cells (PRBC)) in those with beta thalassaemia major

Younger than 6 years

• Not established for use

6 years and older

• See adult dosage 

- Requiring chelation therapy when deferoxamine therapy is contraindicated or inadequate in patients with non-transfusion-dependent thalassaemia syndromes

Younger than 10 years

• No information available

10 years and older

• See adult dosage

---

In paediatric patients with non-transfusion-dependent thalassaemia syndromes, dosing should not exceed 7mg/kg. In these patients, closer monitoring of LIC and serum ferritin is essential to avoid overchelation. In addition to monthly serum ferritin assessments, LIC should be monitored every three months when serum ferritin is ≤800µg/l

Pregnancy 

South African manufacturer recommendations

• Contraindicated
• Safety in pregnancy has not been established
• Should not be used during pregnancy
• Studies in animals have shown some reproductive toxicity. The potential risk for humans is unknown
• Coadministration with hormonal contraceptives can render the contraceptive ineffective; patients are to be advised on the use of non-hormonal method(s) of contraception

International manufacturer recommendations

• Caution; not recommended
• No clinical data on exposed pregnancies are available for deferasirox
• Studies in animals have shown some reproductive toxicity at maternally toxic doses. The potential risk for humans is unknown
• Not to be used during pregnancy unless clearly necessary
• Deferasirox may decrease the efficacy of hormonal contraceptives. Women of childbearing potential are recommended to use additional or alternative non-hormonal methods of contraception

Breastfeeding 

South African manufacturer recommendations

• Contraindicated 
• In animal studies, was found to be rapidly and extensively secreted into maternal milk. It is not known if it is secreted into human milk
• Breastfeeding is not recommended

International manufacturer recommendations

• Caution; not recommended 
• It is not known if deferasirox is secreted into human milk
• In animal studies, deferasirox was found to be rapidly and extensively secreted into maternal milk. No effect on the offspring was noted

Fertility 

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

Renal Impairment 

South African manufacturer recommendations

• eGFR>60ml/min/1.73m²: Caution; no dose adjustment recommended 
• eGFR 40-60ml/min/1.73m²: Caution; dose adjustment recommended 
  Reduce starting dose by 50%  
  Serum creatinine should be monitored monthly in all patients and if necessary daily doses can be reduced by 7mg/kg (fct) or by 10mg/kg (dsp)
• CrCl<60ml/min and/or eGFR<40ml/min/1.73m²: Contraindicated 

International manufacturer recommendations

• eGFR≥60ml/min/1.73m²: No dose adjustment recommended 
• eGFR 40-59ml/min/1.73m²: Caution; dose adjustment recommended 
  Reduce starting dose by 50% 
  Monitor serum creatinine and eGFR during therapy
• eGFR<40ml/min/1.73m²: Contraindicated 

Hepatic Impairment 

South African manufacturer recommendations

• Mild (Child-Pugh Class A): Caution; no dose adjustment recommended 
• Moderate (Child-Pugh Class B): Caution; dose adjustment recommended 
  Starting dose should be reduced by approximately 50%
• Severe (Child-Pugh Class C): Contraindicated 

International manufacturer recommendations

• Mild: Caution; no dose adjustment recommended 
• Moderate (Child-Pugh Class B): Caution; dose adjustment recommended
  Dose should be considerably reduced followed by progressive increase up to a limit of 50%
• Severe (Child-Pugh Class C): Caution; not recommended

Elderly 

• Caution; no dose adjustment recommended  
  Higher frequency of adverse reactions (in particular, diarrhoea) and should be monitored closely for adverse reactions that may require a dose adjustment

Porphyria Information

• Probably not porphyrinogenic (PNP) 

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders 

• Anxiety 
• Sleep disorder 
• Headache 
• Dizziness 
• Fatigue 

Respiratory Disorders 

• Laryngeal pain 

Gastrointestinal Disorders

• Diarrhoea 
• Constipation 
• Nausea and vomiting 
• Abdominal pain 
• Abdominal distension 
• Dyspepsia 
• Gastrointestinal haemorrhage 
• Gastric ulcer (incl. multiple ulcers) 
• Duodenal ulcer 
• Gastritis 
• Oesophagitis 
• Gastrointestinal perforation 
• Acute pancreatitis

Hepatobiliary Disorders

• Increased transaminases 
• Hepatitis 
• Cholelithiasis 
• Hepatic failure 

Genitourinary Disorders

• Increased blood creatinine 
• Decreased CrCl
• Proteinuria 
• Renal tubular disorder (acquired Fanconi syndrome)
  - Hyperammonaemic encephalopathy (See additional prescribing points) 
• Glycosuria 
• Acute renal failure 
• Tubulointerstitial nephritis 
• Nephrolithiasis 
• Renal tubular necrosis 

Endocrine and Metabolic Disorders

•  Metabolic acidosis 

Skin and Subcutaneous Tissue Disorders

• Rash 
• Pruritus
• Pigmentation disorder 
• Severe cutaneous adverse reactions
  - Stevens-Johnson syndrome (SJS) 
  - Drug reaction with eosinophilia and systemic symptoms (DRESS) 
  - Toxic epidermal necrolysis (TEN) 
• Urticaria 
• Erythema multiforme 
• Alopecia 
• Hypersensitivity vasculitis 

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions 
  - Anaphylactic reactions
  - Angioedema 
• Fever  
• Pancytopenia 
• Thrombocytopenia 
• Aggravated anaemia 
• Neutropenia 
• Oedema 

Sensory Disorders 

• Cataract 
• Lens opacity
• Maculopathy 
• Optic neuritis 
• Decreased hearing
• Deafness 

• Other iron chelating agents 
• Repaglinide 
• Potent UDP-glucuronosyltransferase (UGT) inducers
• Rifampicin
• Carbamazepine
• Phenytoin 
• Phenobarbital
• Ritonavir 
• Cholestyramine 
• CYP3A4 substrates 
• Midazolam 
• Ciclosporin 
• Simvastatin 
• Hormonal contraceptive agents 
• Bepridil
• Ergotamine
• CYP2C8 substrates 
• Paclitaxel 
• CYP1A2 substrates
• Theophylline 
• Clozapine
• Tizanidine
• Aluminium-containing antacids 
• Ulcerogenic agents
• Non-steroidal anti-inflammatory drugs
• Acetylsalicylic acid at high doses
• Corticosteroids 
• Oral bisphosphonates
• Anticoagulants 
• Busulfan (See additional prescribing points)

Other interactions

• High-fat meal 

• Serum ferritin
• Full blood count with differential
• Electrolytes 
• Renal function (See additional prescribing points)
  - Serum creatinine
  - eGFR
  - Cystatin C
• Hepatic function
  - Serum transaminases
  - Bilirubin
  - Alkaline phosphatase
• Hepatic iron concentration
• Urinalysis
  - Urine protein
• Auditory examination
• Ophthalmic examination

Specific cases may require 

• Blood glucose
• Body weight, height and sexual development (paediatrics)
• Acid-base balance
• Ammonia
• Glycosuria
• Cardiac function

Additional observations

• Cumulative number of red blood cell units received 
• Signs/symptoms of toxicities in
  - Elderly
  - Paediatric patients experiencing volume depletion or overchelation
  - Patients receiving nephrotoxic agents 
• Signs/symptoms of
  - Dermatologic toxicity
  - Gastrointestinal ulcers
  - Haemorrhage
  - Hypersensitivity
  - Renal tubular toxicity

Renal function

• Serum creatinine should be assessed in duplicate before initiating therapy
• Serum creatinine, CrCl (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 (including switch of formulation), and monthly thereafter
• Maintain adequate hydration in patients who experience volume-depleting events, such as diarrhoea or vomiting
• Monitor renal function more frequently in paediatric patients in the presence of renal toxicity risk factors, including episodes of dehydration, fever and acute illness that may result in volume depletion or decreased renal perfusion
• For adult patients, the daily dose may be reduced by 10mg/kg (dsp) or 7mg/kg (fct) if a non-progressive rise in serum creatinine by >33% above the average of the pre-treatment measurements is seen at two consecutive visits, and cannot be attributed to other causes (South African manufacturer recommendations)
• For paediatric patients, the dose may be reduced by 10mg/kg (dsp) or 7mg/kg (fct)  if serum creatinine levels rise above the age- appropriate upper limit of normal at two consecutive visits (South African manufacturer recommendations)
• If serum creatinine increases 2-fold above the baseline, reduce dose by up to 50%. Patients with observed reduction in renal function (eGFR<40ml/min/1.73m²), discontinue treatment (International manufacturer recommendations)

Hyperammonaemic encephalopathy

• 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
• 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 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 therapy

Coadministration with busulfan

• Concomitant administration of deferasirox and busulfan resulted in an increase of busulfan exposure (area under the curve [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

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. 

Tablet dispersible 125mg

• Exjade (Novartis) originator (Discontinued: 05/03/2021)

Tablet dispersible 250mg

• Exjade (Novartis) originator

Tablet dispersible 500mg

• Exjade (Novartis) originator

Film-coated tablet 90mg

• Deferasirox Cipla (Cipla Medpro) 
• Jadenu (Novartis) originator
• Nujade (Cipla Medpro) 

Film-coated tablet 180mg

• Deferasirox Cipla (Cipla Medpro) 
• Jadenu (Novartis) originator
• Nujade (Cipla Medpro) 

Film-coated tablet 360mg

• Deferasirox Cipla (Cipla Medpro) 
• Jadenu (Novartis) originator
• Nujade (Cipla Medpro)