Active Ingredient: Deferasirox
Deferasirox 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 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:
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 14 milligrams deferasirox per kilogram of body weight, once daily. The maximum allowed total dose is 28 milligrams deferasirox per kilogram of body weight daily.
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.
Due to different pharmacokinetic profiles, a 30% lower dose of deferasirox film-coated tablets is needed in comparison to the recommended dose for deferasirox dispersible tablets.
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) | |
| 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 steps (every 3-6 months) | Increase 3.5 – 7 mg/kg/day Up to 28 mg/kg/day | >2,500 µg/l | |
| Decrease 3.5 – 7 mg/kg/day In patients treated with doses >21 mg/kg/day | ≤2,500 µg/l | ||
| - When target is reached | 500-1,000 µg/l | ||
| Maximum dose | 28 mg/kg/day | ||
| Consider interruption | <500 µg/l |
The recommended initial daily dose of deferasirox is 14 mg/kg body weight.
An initial daily dose of 21 mg/kg of deferasirox 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 of deferasirox 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.
For patients already well managed on treatment with deferoxamine, a starting dose of deferasirox 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). 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.
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 possible. Doses above 28 mg/kg are not recommended because there is only limited experience with doses above this level.
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 ≤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.
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.
The dosing recommendations for paediatric patients aged 2 to 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 and 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.
The safety and efficacy of deferasirox in children from birth to 23 months of age have not been established. No data are available.
It should be taken once a day, preferably at the same time each day.
It may be taken on an empty stomach or with a light meal.
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