Maximum dose of Desferrioxamine for Thalassaemia

• Based on the guidelines the dose recommended is 50-60mg/kg.
• To achieve a negative iron balance, a dose of 50mg/kg/day at least 5 days a week is needed
• Overall survival is related to the number of hours per week that deferoxamine is infused. Deferoxamine is more effective when a lower dose is circulated through the body over a longer period of time than when a higher dose is circulated over a short period of time. Therefore, time of exposure is more important than total dose once doses of 60 mg/kg per day are being utilized
• Patients with high degrees of iron loading or at increased risk of cardiac complications receive adequate doses
• Iron excretion with desferrioxamine increases with dose, with body iron stores and in vitamin C deficient patients with the addition of vitamin C

CHILDREN

• Caution in children below 3 years due to potential toxicity to bone development and growth
• children is 20-40mg/kg. this is because a higher dose would affect skeletal and growth.

ADULTS

• 50-60mg/kg for a minimum of 6 times a week
• Rescue Therapy
• A dose of at least 50 mg/kg/day and not exceeding 60 mg/kg/day is recommended as a 24-hour infusion
• Higher doses have been used by some clinicians however DFO is not licensed at these doses and the risk of retinopathy increases
• As ferritin falls, the dose but preferably not the duration of treatment can be reduced, in line with the therapeutic index

DOSE ADJUSTMENTS

• At low ferritin levels, the dose of desferrioxamine may need to be reduced and desferrioxamine-related toxicities monitored particularly carefully. Dose reductions can be made using the therapeutic index
• Therapeutic index = mean daily dose (mg/kg)* / ferritin (Ìg/l)
• The aim is to keep the index < 0.025 at all times *mean daily dose = (actual dose received on each infusion x doses per day /7)
• To avoid wasting a costly drug such as desferrioxamine, the dose can be adjusted to the nearest whole vial (500 mg or 2 g), alternating dose volumes between the higher and lower number of vials to achieve the desired mean daily dose
• optimisation would include increasing the dose to 60 mg/kg/day, increasing the duration of infusion (even up to 24 hours per day) and the number of days of therapy (up to 7 days per week

REFERENCES

1. Guidelines for the Clinical Management of Thalassaemia 2nd edition
2. Malaysian Thalassaemia CPG
3. Treating Thalassaemia Chelation- Desferal. http://thalassemia.com/treatment-chelation-desferal.aspx#gsc.tab=0