Pediatric Clinics of North America - CIPERJ

476 KWIATKOWSKI
cells, deferasirox was able to extract intracellular iron and restore ironimpaired
contractility [88]. Similarly, in iron-overloaded gerbils, deferasirox
was as effective as deferiprone in reducing cardiac iron content [89]. Furthermore,
in a preliminary report of 23 patients receiving deferasirox at doses of
10 to 30 mg/kg per day, cardiac iron content measured by T2* MRI
improved from an average of 18 ms to 23 ms over a treatment period of
13 months [90]. Further studies are needed to confirm the effect of deferasirox
on cardiac iron and cardiac disease.
Adverse effects
The toxicity profile of deferasirox is similar across disease states and
seems tolerable. Gastrointestinal disturbances, including nausea, vomiting,
and abdominal pain, are common [15]. Although usually transient and
dose related, these symptoms have led to discontinuation of the drug in
some patients in clinical trials and in actual practice. The gastrointestinal
side effects may be related to lactose intolerance as lactose is present in
the drug preparation [16]. Diffuse, maculopapular skin rashes are reported
in approximately 10% of subjects receiving deferasirox [15,16,28]. The
rash often improves, even if the drug is continued. More than one third
of patients experience mild elevations in serum creatinine levels, but few
patients experience elevations beyond the normal range [15,16]. In some patients,
the creatinine returned to baseline without dose modification,
whereas in others, elevated or fluctuating levels persisted. Elevations in hepatic
transaminases to more than 5 times baseline values also are reported
[15,16]. The abnormalities are transient in some, even with continued
administration of drug, whereas in others the abnormalities resolved with
discontinuation of drug and recurred with drug reinstitution, suggesting
causality. Fulminant hepatic failure is reported in rare cases, often in patients
who have comorbidities. Cataracts or lenticular opacities and audiotoxicity
are reported at low rates, similar to deferoxamine [15,16]. To date,
the use of deferasirox is reported for more than 350 pediatric patients and
the toxicity profile is similar to that seen in adults [15,16,28,86,91]. In addition,
no adverse effects on growth or sexual development have been found,
although longer follow-up is needed to assess fully for this potential complication.
Agranulocytosis is not seen with deferasirox administration and the
rare reports of neutropenia with deferasirox all are believed related to the
underlying hematologic disorder and unlikely a drug effect.
Long-term data on treatment with deferasirox are lacking, and less common
side effects may become evident only when larger numbers of patients
are treated with the drug for a longer duration. Ongoing extension studies
and postmarketing surveillance will help better define the long-term efficacy
and safety profile of this drug. In addition, the use of deferasirox in combination
with other chelators is not yet tested, and studies are needed to evaluate
the efficacy and safety of such an approach before combination therapy
can be recommended for clinical use.