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4-[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid; CGP-72670; ICL-670; ICL-670A
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Transfusion-induced hemosiderosis
Deferasirox (marketed as Exjade, Desirox, Defrijet, Desifer...) is an iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. It is the first oral medication approved in the USA for this purpose.
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Deferasirox is a synthetic, orally bioavailable, achiral, tridentate triazole derived from salicylic acid with iron-chelating activity. It is an Iron Chelator. The mechanism of action of deferasirox is as an Iron Chelating Activity, and Cytochrome P450 3A4 Inducer, and Cytochrome P450 2C8 Inhibitor, and Cytochrome P450 1A2 Inhibitor. Deferasirox chelates iron at a 2:1 (ligand:iron) ratio. Because of its oral availability and long plasma half-life, this agent may be superior to desferrioxamine (desferal, DFO), which is orally inactive and has a short plasma half-life.

Iron accumulation is a consequence of regular red cell transfusions, and can occur as a result of ineffective erythropoiesis secondary to increased intestinal iron absorption, in patients with various anemias. Without appropriate treatment, iron overload can lead to increased morbidity and mortality. Deferasirox is an oral iron chelator effective for reduction of body iron in iron-overloaded patients with transfusion-dependent anemias and non-transfusion-dependent thalassemia, with a well-established safety profile. This review summarizes the clinical pharmacokinetics, pharmacodynamics, and drug-drug interaction profile of deferasirox, and the claims supporting once-daily dosing for effective chelation.

Tanaka, C. (2014). Clinical pharmacology of deferasirox. Clinical pharmacokinetics, 53(8), 679-694.

The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed(chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults.

Trachtenberg, F., Vichinsky, E., Haines, D., Pakbaz, Z., Mednick, L., Sobota, A., ... & Giardina, P. J. (2011). Iron chelation adherence to deferoxamine and deferasirox in thalassemia. American journal of hematology, 86(5), 433-436.

Thirty-nine children with Fanconi aplastic anemia (FAA) have been followed up in our center between January 2008 and November 2010. Eight of these children (20%) with a transfusional iron overload had been undergoing deferasirox treatment during the study period. In the English literature, transfusional iron overload and the use of an iron chelator in children with FAA has not yet been evaluated. Here, we have presented the effectivity and tolerability of deferasirox in children with FAA and a transfusional iron overload. Before the deferasirox treatment, the mean serum ferritin level was 3377 ± 2200 ng/mL. After a mean 13.6-month treatment duration, the mean ferritin level decreased to 2274 ± 1300 ng/mL (P<0.05). In our series, 3 patients had renal and 3 had hepatic toxicity during the treatment. Two patients had peliosis hepatis and 2 had congenital renal abnormalities before the treatment. There may be differences in the side-effect profiles of deferasirox treatment in patients with FAA. In our series, despite the low number of cases, nephrotoxicity and hepatotoxicity were common side effects instead of gastrointestinal disturbances reported in other studies. Deferasirox is an oral, easily applicable, and effective iron chelator; baseline hepatotoxicity and nephrotoxicity may increase the development of toxic side effects in children with FAA. Patients with FAA receiving deferasirox treatment should be followed up closely for these side effects.

Tunç, B., Tavil, B., Karakurt, N., Yarali, N., Azik, F. M., Kara, A., ... & Ozkasap, S. (2012). Deferasirox therapy in children with Fanconi aplastic anemia. Journal of pediatric hematology/oncology, 34(4), 247-251.

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