Deferasirox

(USAN, rINN)
Deferasirox Chemical formula
Synonyms: CGP-72670; Déférasirox; Deferasiroxum; ICL-670; ICL-670A. 4[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid.
Cyrillic synonym: Деферазирокс.

💊 Chemical information

Chemical formula: C21H15N3O4 = 373.4.
CAS — 201530-41-8.
ATC — V03AC03.
ATC Vet — QV03AC03.

💊 Adverse Effects and Precautions

The commonest adverse effects with deferasirox are dose-related gastrointestinal disorders, such as nausea, vomiting, diarrhoea, and abdominal pain; diarrhoea may be more common in young children. Skin rashes are also common and may respond to a reduction in dose. Other adverse effects include headache, pyrexia, and cough. Dose-dependent increases in serum creatinine are common and proteinuria may also occur; there have been reports of acute renal failure, including fatalities. Serum creatinine should be measured before starting deferasirox, and renal function should be assessed weekly for the first month (particularly in patients with risk factors for renal disease) and for a month after dosage increases, then monthly thereafter; tests for proteinuria should also be performed monthly. The dose should be reduced or treatment stopped if persistent increases in serum creatinine occur. Liver enzyme values may increase in patients receiving deferasirox, and cases of hepatitis have occurred; gallstones and related biliary disorders have also been reported. Liver enzymes should be monitored monthly and treatment should be stopped if persistent increases occur. As with other iron chelators, hearing loss and visual disorders, including cataracts, have occurred. Audiological and ophthalmological tests should be performed before starting deferasirox and then every 12 months. Serum ferritin should be measured monthly. In children, annual assessment of growth and development is also recommended. There have been rare reports of blood disorders, some of which have been fatal, including agranulocytosis, neutropenia, and thrombocytopenia, in patients taking deferasirox. Blood counts should be monitored regularly.

💊 Interactions

Deferasirox should not be given with aluminium-containing antacids since there is a possibility that it may chelate aluminium.

💊 Pharmacokinetics

Deferasirox is absorbed from the gastrointestinal tract and peak plasma concentrations occur about 1.5 to 4 hours after ingestion. The absolute bioavailability is about 70% but is increased in the presence of food. Deferasirox is about 99% bound to plasma proteins, mainly albumin. It is metabolised by glucuronidation and is excreted mainly in the faeces via bile, as metabolites and as unchanged drug; there is a possibility that enterohepatic recycling may occur. About 8% of a dose is excreted in the urine. The mean elimination half-life is about 8 to 16 hours.

💊 Uses and Administration

Deferasirox is an orally active iron chelator that is used in the management of chronic iron overload due to blood transfusion. It is available as tablets that are made into a suspen sion immediately before use. The usual initial dose in adults and children 2 years of age and older is 20 mg/kg once daily, taken on an empty stomach at least 30 minutes before food. Serum ferritin should be monitored monthly and the dose should be adjusted every 3 to 6 months as necessary. The maximum recommended dose is 30 mg/kg daily.
1. VanOrden HE, Hagemann TM. Deferasirox—an oral agent for chronic iron overload. Ann Pharmacother 2006; 40: 1110–17
2. Stumpf JL. Deferasirox. Am J Health-Syst Pharm 2007; 64: 606–16
3. Yang LPH, et al. Deferasirox: a review of its use in the management of transfusional chronic iron overload. Drugs 2007; 67: 2211–30.

💊 Preparations

Proprietary Preparations

Arg.: Exjade; Austral.: Exjade; Chile: Exjade; Cz.: Exjade; Fr.: Exjade; Gr.: Exjade; Hung.: Exjade; Indon.: Exjade; Malaysia: Exjade; NZ: Exjade; UK: Exjade; USA: Exjade.
Published October 23, 2018.