Deferasirox

Generic name
Deferasirox
Brand name
ATC Code
V03AC03
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Deferasirox

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

The total exposure of adolescents (12 to 17 years) and children (2 to 12 years) to
deferasirox after single and multiple doses was lower than in adult patients. In children younger than 6 years, the exposure was about 50% lower than in adults. Given the dosage is adjusted to the individual based on the response, there is no reason to expect this to have clinical consequences.

 

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Transfusion-related iron accumulation
  • Oral
    • Film-coated tablet
      • 2 years up to 18 years
        [1]
        • Initial dose 14 mg/kg/day in 1 dose. Max: 28 mg/kg/day. Titrate the initial dose in steps of 3.5-7 mg/kg/day based on the serum ferritin.
          • If a reduction of the iron level is not necessary and < 7 ml/kg/month of red blood cells is being given:
            initial dose 7 mg/kg/day in a single dose
          • If a reduction of the iron level is necessary and >14 ml/kg/month of red blood cells is being given:
            starting dose 21 mg/kg/day in a single dose
          .
          • When switching from deferoxamine to deferasirox: 33% of the deferoxamine dose = deferasirox dose.
          • Children aged 2 to 5 years might need higher doses than adults (see kinetic data)
    • Orodispersable tablet
      • 2 years up to 18 years
        [1]
        • Initial dose: 20 mg/kg/day in 1 dose. Max: 40 mg/kg/day. Titrate the initial dose in steps of 5-10 mg/kg/day based on the serum ferritin.
          • If a reduction of the iron level is not necessary and < 7 ml/kg/month of red blood cells is being given:
            starting dose 10 mg/kg/day in a single dose
          • If a reduction of the iron level is necessary and >14 ml/kg/month of red blood cells is being given:
            starting dose 30 mg/kg/day in a single dose
          • When switching from deferoxamine to deferasirox: 50% of the deferoxamine dose = deferasirox dose.
          .

        • Children aged 2 to 5 years might need higher doses than adults (see kinetic data)
Non-transfusion-dependent thalassaemia syndromes
  • Oral
    • Film-coated tablet
      • 10 years up to 18 years
        [1]
        • 7 mg/kg/day in 1 dose. Max: 14 mg/kg/day. Adjust dosage every 3-6 months based on the liver iron concentration (LIC) and serum ferritin: LIC ≥7 mg Fe/g dry weight or serum ferritin > 2000 μg/l: increase dose by 3.5-7 mg/kg/day
          LIC < 7 mg Fe/g dry weight or serum ferritin < 2000 μg/l: decrease doseby 3.5-7 mg/kg/day.

        • Chelation therapy should only be started if there are indications of iron accumulation (liver iron concentration [LIC] ≥5 mg Fe/g dry weight [dw] or serum ferritin is continually >800 μg/l).
          When an appropriate iron level in the body has been achieved (LIC <3 mg Fe/g dw or serum ferritin < 300 μg/l), the treatment should be stopped

    • Orodispersable tablet
      • 10 years up to 18 years
        [1]
        • 10 mg/kg/day in 1 dose. Max: 20 mg/kg/day. Adjust dosage every 3-6 months based on the liver iron concentration (LIC) and serum ferritin:
          • LIC ≥7 mg Fe/g dry weight or serum ferritin > 2000 μg/l: increase the dose by 5-10 mg/kg/day
          • LIC <7 mg Fe/g dry weight or serum ferritin  < 2000 μg/l: decrease the dose by 5-10 mg/kg/day
          .

        • Chelation therapy should only be started if there are indications of iron accumulation (liver iron concentration [LIC] ≥5 mg Fe/g dry weight [dw] or serum ferritin is continually >800 μg/l).
          When an appropriate iron level in the body has been achieved (LIC <3 mg Fe/g dw or serum ferritin < 300 μg/l), the treatment should be stopped.

Renal impaiment in children > 3 months

Adjustment in renal impairment as specified:

GFR 50-80 ml/min/1.73 m2
Adjustment not necessary
GFR 30-50 ml/min/1.73 m2
Do not administer
GFR 10-30 ml/min/1.73 m2
Do not administer
GFR < 10 ml/min/1.73 m2
Do not administer

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Diarrhoea is reported more often in paediatric patients aged 2-5 years than in older patients. Renal tubulopathy was primarily 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.In two clinical studies, growth and sexual development of paediatric patients treated with deferasirox for up to 5 years were not affected

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

In pediatric patients with non-transfusion-dependent thalassemia syndromes, the dose should not exceed 10 mg/kg. In these patients, more close monitoring of the LIC and serum ferritin is necessary to prevent excessive chelation. In addition to monthly determinations of serum ferritin, the LIC should be checked every three months in these patients when serum ferritin is ≤800 μg/l.

Reduce daily dose by 7 mg/kg (film-coated tablet) or 10 mg/kg (dispersible tablet), if necessary, if the following renal parameters are observed at two consecutive check-ups and there is no other explanation: a serum creatinine higher than age appropriate ULN and/or a creatinine clearance < 90 ml/min.

Interrupt treatment if this does not result in a serum creatinine value ≤ 33% above the mean of the measurements prior to treatment and a calculated creatinine clearance > 90 ml/min.

In children, monitor growth and (sexual) development annually. Diarrhea has been reported more frequently in children 2-5 y than in the elderly. Care should be taken to maintain adequate hydration in patients who develop diarrhoea or vomiting.

Experience in children with non-transfusion-related thalassemia is limited; close monitoring is necessary.

Severe forms of renal tubulopathy and renal failure associated with alterations of consciousness in the context of hyperammonaemic encephalopathy have been reported, particularly in children. Measure ammonia levels in case of unexplained changes in mental status.

 

 

 

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

ALL OTHER THERAPEUTIC PRODUCTS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Antidotes
V03AB15
V03AB14
Iron chelating agents
V03AC02
V03AC01
Detoxifying agents for antineoplastic treatment
V03AF03
V03AF01
V03AF07
Drugs for treatment of hypoglycemia
V03AH01
DETOXIFYING AGENTS FOR ANTINEOPLASTIC TREATMENT
V03AF03
V03AF01
V03AF07

Reference

  1. Novartis Pharma BV, SPC Exjade (EU/1/06/356/001-003) 24-11-2017, www.ema.europa.eu

Changes

Therapeutic Drug Monitoring


Overdose