|Pronunciation||de FER a sir ox|
|Trade names||Exjade, Jadenu, others|
|Other names||CGP-72670, ICL-670A, IC L670|
|Drug class||Iron chelator|
|Main uses||Chronic iron overload due to blood transfusions|
|Side effects||Kidney problems, nausea, diarrhea, heart burn, rash, itchiness, liver problems|
|Typical dose||7 to 21 mg/kg OD|
|Elimination half-life||8 to 16 hours|
|Excretion||Fecal (84%) and renal (8%)|
|Chemical and physical data|
|Molar mass||373.368 g·mol−1|
|3D model (JSmol)|
|Density||1.4±0.1 g/cm3 |
Deferasirox, sold under the brand name Exjade among others, is a medication used for chronic iron overload in those receiving long-term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. It is generally only when deferoxamine is not sufficient. It is taken by mouth.
Common side effects include kidney problems, nausea, diarrhea, heart burn, rash, itchiness, and liver problems. Other side effects may include metabolic acidosis, bone marrow suppression, and gastrointestinal bleeding. It should not be used in people with kidney problems. It is believed to be harmful in pregnancy. It is an iron chelator.
Deferasirox was approved for medical use in the United States in 2005 and Europe in 2006. In the United Kingdom a month at a dose of 360 mg per day costs the NHS about £500 as of 2021. In the United States this amount costs about 190 USD. Generic versions were approved in 2020.
It is typically started at a dose of 7 to 21 mg/kg per day.
Deferasirox ranked second on the list of drugs most frequently suspected in reported patient deaths compiled for 2019 by the Institute for Safe Medical Practices, with 1320 suspected deaths. A boxed warning was added in the same year with regard to kidney failure, liver failure and gastrointestinal bleeding. It is suspected that the main driver of this spike in suspected deaths relates to the re-analysis of adverse event data by Novartis.
The half-life of deferasirox is between 8 and 16 hours allowing once a day dosing. Two molecules of deferasirox are capable of binding to 1 atom of iron which are subsequently eliminated by fecal excretion. Its low molecular weight and high lipophilicity allows the drug to be taken orally unlike deferoxamine which has to be administered by IV route (intravenous infusion). Together with deferiprone, deferasirox seems to be capable of removing iron from cells (cardiac myocytes and hepatocytes) as well as removing iron from the blood.
Deferasirox can be prepared from simple commercially available starting materials (salicylic acid, salicylamide and 4-hydrazinobenzoic acid) in the following two-step synthetic sequence:
The condensation of salicyloyl chloride (formed in situ from salicylic acid and thionyl chloride) with salicylamide under dehydrating reaction conditions results in formation of 2-(2-hydroxyphenyl)-1,3(4H)-benzoxazin-4-one. This intermediate is isolated and reacted with 4-hydrazinobenzoic acid in the presence of base to give 4-(3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl)benzoic acid (deferasirox).
Society and culture
In July 2020, Teva discontinued deferasirox.
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