ICL670A: Preclinical Profile

The iron chelator deferasirox protects mice from mucormycosis through iron starvation

“…In preclinical investigations of deferasirox, no toxicities were seen in non-iron-overloaded marmosets after 39 weeks of treatment with up to 40 mg/kg/d, and during subacute treatment (4 weeks), doses up to 65 mg/kg/d were well tolerated, with no adverse effects (27). In clinical investigations (25,28,35), deferasirox was very well tolerated at doses up to 40 mg/kg/d for up to 12 days, and over months to years, at up to 30 mg/kg/d.…”

“…Furthermore, it is known that deferasirox chelation is specific for iron and that other trace metals and cations are not affected by the drug (27,28). However, deferasirox was associated with an enhancement of the suppressed inflammatory response in diabetic ketoacidotic mice.…”

Thalassemia Major: Who Is Afraid of Serum Ferritin below 500 μg/l?

“…The actual condition of a patient with normal or near-normal serum ferritin seems to be complex; low serum ferritin values, even in the normal range, do not per se exclude iron excess, particularly in the heart. Only the incidence of intermittent proteinuria in patients treated with deferasirox, even though remaining reversible in all cases, seems to be clearly dependent on the iron loading status, as demonstrated in preclinical studies [5]. The few negative effects with a suspected causal link to low levels of ferritin are nonspecific and have not been confirmed using comparative analyses of different levels of serum ferritin.…”

Pharmacokinetics, Metabolism, and Disposition of Deferasirox in β-Thalassemic Patients with Transfusion-Dependent Iron Overload Who Are at Pharmacokinetic Steady State

“…As a result, the most common difficulty associated with long-term deferoxamine is erratic compliance with therapy (Kushner et al, 2001). The need for an iron chelator that can be given orally has been recognized for a long time.Deferasirox (ICL670, Exjade; Novartis Pharma AG, Basel, Switzerland) is a potent and specific iron chelator, recently approved as first-line therapy for blood transfusion-related iron overload; it binds Fe 3ϩ in a 2:1 ratio (Nick et al, 2002). The recommended initial daily dose is 20 mg/kg b.wt., rounded to the nearest available tablet strength; the currently recommended maximal dose is 30 mg/kg/day .…”

“…Deferasirox (ICL670, Exjade; Novartis Pharma AG, Basel, Switzerland) is a potent and specific iron chelator, recently approved as first-line therapy for blood transfusion-related iron overload; it binds Fe 3ϩ in a 2:1 ratio (Nick et al, 2002). The recommended initial daily dose is 20 mg/kg b.wt., rounded to the nearest available tablet strength; the currently recommended maximal dose is 30 mg/kg/day .…”