Pediatric Clinics of North America - CIPERJ

468 KWIATKOWSKI
[42]. Chelation therapy with deferoxamine prevents other organ toxicities,
such as diabetes [37].
Local infusion site reactions, including induration and erythema,
commonly are seen with administration of deferoxamine. Low zinc levels
also can develop with deferoxamine use. Other adverse effects, including
high frequency hearing loss, ophthalmologic toxicity [43], growth retardation,
and skeletal changes, including rickets-like lesions and genu valgum
[44], are more common when patients receive high doses of deferoxamine
relative to their total body iron burden and can be minimized by maintaining
an optimal chelator dose [45]. Acute pulmonary toxicity with respiratory
distress and hypoxemia and a diffuse interstitial pattern on chest roentgenogram
is reported with the administration of high doses of deferoxamine
(10 to 20 mg/kg per hour) [46].
The major limitation to deferoxamine is the need to administer the drug parenterally,
which is painful and time consuming. As a result, poor compliance
remains a significant problem with administration of this drug, and preventable,
premature deaths related to iron overload continue to occur [47,48].
Characteristics of an ideal chelator
The limitations of treatment with deferoxamine have led investigators to
search for more acceptable iron chelators to be used in the management of
iron overload. An optimal chelator should have adequate gastrointestinal
absorption to allow oral administration, a long half-life permitting once
or twice daily dosing, and a high affinity for iron with lesser affinities for
other metals. The chelator should be able to induce iron excretion at
a rate of at least 0.5 mg/kg per day to offset the amount of transfusional
iron loading, and should be able to remove excess cardiac iron. Finally,
toxicities associated with the drug should be minimal and manageable.
Deferiprone
Pharmacology
Deferiprone, or 1,2 dimethyl-3-hydroxypyrid-4-1 (Ferriprox), was the
first orally active chelator studied extensively for the treatment of transfusional
iron overload, introduced into clinical trials 20 years ago (see Table 2).
Most studies have been open-label, noncomparative studies, often including
patients who had a history of inadequate iron chelation, but a few randomized
trials comparing deferiprone to deferoxamine are reported. A substantial
amount of data on the safety and efficacy of the drug has been acquired,
but considerable controversy surrounding the drug exists. In the European
Union, deferiprone is approved for use for patients in whom deferoxamine
therapy is contraindicated or inadequate, but the drug is not approved for