Pediatric Clinics of North America - CIPERJ

ORAL IRON CHELATORS
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use in North America and currently is available only to a limited number of
patients through expanded access programs or research trials.
Deferiprone is a bidentate chelator, which forms a 3:1 chelator:iron
complex. Given its short plasma half-life of 1.5 to 2.5 hours [49,50], the
drug usually is dosed 3 times daily, although regimens of 2 or 4 times daily
have been explored [51]. The usual daily dose is 75 mg/kg per day, but
higher doses have been studied [51]. Deferiprone induces iron excretion
almost exclusively in the urine, with minimal contribution from fecal elimination
[52,53].
Efficacy
Urinary iron excretion with deferiprone at 75 mg/kg is comparable to
that induced by deferoxamine at a dose of 50 mg/kg [52,53]. Given that
deferoxamine induces fecal iron excretion, total iron excretion with deferiprone
is approximately 60% of that with deferoxamine at these doses
[52]. The mean urinary iron excretion with deferiprone at 75 mg/kg was
0.48 mg/kg per day in one study, a level predicted to maintain or decrease
iron stores in most patients [52]. Significant interpatient variability exists,
however, so not all patients can achieve a negative iron balance at this
dose. For example, in one study, urinary iron excretion ranged from 11.2 to
74.9 mg per day at a 75 mg/kg dosing level [54]. Higher doses of deferiprone,
90 to 119 mg/kg, induced greater urinary iron excretion and may be beneficial
for patients who have inadequate responses at lower doses [51,54,55].
Short-term studies of deferiprone generally show a reduction [51,56–58]
or stabilization [59] in serum ferritin levels over a treatment period of
1 year or less. Similarly, studies that assessed the response to deferiprone
over longer treatment periods, of 3 to 4 years, show reduced [30,54,60,61]
or stable [62,63] mean serum ferritin levels. Similar responses are shown
across different disease states, including sickle cell disease and thalassemia.
A small proportion of patients demonstrated a significant increase in
serum ferritin levels while receiving long-term deferiprone [30,61–63]. In
a group of 151 Italian patients who received deferiprone for 3 years or
more, 20% of subjects had clinically significant rises in ferritin levels during
the first year of treatment [61]. In general, patients who had higher baseline
ferritin levels showed a greater reduction in serum ferritin than those who
had lower pretreatment ferritin levels. In a long-term, multicenter study,
84 patients received deferiprone for 4 years at a mean daily dosage of 73
mg/kg. Mean serum ferritin levels declined significantly from 3661 to 2630
mg/L in the group whose baseline serum ferritin was above 2500 mg/L,
whereas ferritin levels remained stable in those with baseline values less
than 2500 mg/L [63].
Studies on the effect of chelation with deferiprone on liver iron content
have mixed results [30,57,62,64,65]. In a report of 21 patients who received
deferiprone (75 mg/kg per day), mean liver iron concentration assessed by