Adult: For transfusion-related chronic Fe overload: Initially, 20 mg/kg once daily. Adjust dose in increments or decrements of 5-10 mg/kg, 3-6 mthly when needed. Max: 40 mg/kg daily. Discontinue treatment if serum-ferritin concentrations consistently fall below 500 mcg/L. For Fe overload of non-transfusion dependent thalassaemia syndromes: Initially, 10 mg/kg once daily, may increase to 20 mg/kg daily after 4 wk, if the baseline liver-Fe concentration is >15 mg Fe/g of liver dry wt. Adjust dose in increments or decrements of 5-10 mg/kg, 3-6 mthly when needed. Max: 20 mg/kg daily. Discontinue treatment if serum-ferritin concentrations consistently fall below 300 mcg/L. Child: For transfusion-related chronic Fe overload: 2-5 yr Initially, 20 mg/kg once daily. May require higher titration doses. >5-17 yr Same as adult dose. For Fe overload of non-transfusion dependent thalassaemia syndromes: Max: 10 mg/kg daily.
Renal Impairment
CrCl (mL/min)
Dosage
<60
Contraindicated.
Hepatic Impairment
Moderate: Considerably reduce dose followed by progressive increase up to a limit of 50%. Severe: Contraindicated.
Administration
Should be taken on an empty stomach. Take at least 30 min before meals preferably at the same time daily. Disperse tab completely by stirring in 100-200 mL of water/apple juice/orange juice until a fine susp is obtained; consume entire content. Rinse the glass w/ a little water/juice to resuspend any residue & drink remainder. Do not disperse tab in fizzy drinks/milk. Swallow whole, do not chew/break/crush tab. Do not take w/ Al-containing antacids.
Reconstitution
Completely disperse tab by stirring in water, orange or apple juice. Disperse <1 g in 105 mL and ≥1 g in 210 mL of liq. Following admin, any residue should be resuspended in a small vol of liq.
Monitor serum ferritin concentrations and tests for proteinuria mthly. Measure liver enzymes and bilirubin prior to, 2 wkly during the 1st mth and mthly thereafter. Perform auditory testing and ophthamologic examination before starting treatment and yrly thereafter. Monitor renal function and CBC before starting treatment and regularly during therapy.
May chelate Al when used w/ Al-containing antacids. Decreased exposure w/ colestyramine and potent inducers of UGT enzymes (e.g. carbamazepine, rifampicin, phenytoin). May increase serum concentration of CYP1A2 (e.g. duloxetine, theophylline) and CYP2C8 (e.g. repaglinide, paclitaxel) substrates, and decrease serum concentrations of CYP3A4 substrates (e.g. ciclosporin, hormonal contraceptives, simvastatin).
Food Interaction
Food variably increases bioavailability.
Action
Description: Mechanism of Action: Deferasirox is an orally active chelator that is selective for Fe (III). It is a tridentate ligand that binds Fe w/ high affinity in a 2:1 ratio. It promotes excretion of Fe, primarily in the faeces and has low affinity for Zn and Cu. Pharmacokinetics: Absorption: Absorbed from the GI tract. Increased bioavailability in the presence of food. Absolute bioavailability: Approx 70%. Time to peak plasma concentration: Approx 1.5-4 hr. Distribution: Distributed into erythrocytes (5%). Volume of distribution: Approx 14 L. Plasma protein binding: Approx 99% (mainly albumin). Metabolism: Undergoes hepatic metabolism via glucuronidation by uridine diphosphate glucuronosyltransferase (UGT) 1A1 and to a lesser extent by UGT1A3. Minimally metabolised (approx 8%) by oxidative cytochrome P-450 enzymes. Excretion: Excreted mainly in the faeces, via bile as metabolites and unchanged drug; via urine (approx 8%). Mean elimination half-life: Approx 8-16 hr.
Chemical Structure
Source: National Center for Biotechnology Information. PubChem Database. Deferasirox, CID=214348, https://pubchem.ncbi.nlm.nih.gov/compound/Deferasirox (accessed on Jan. 20, 2020)
V03AC03 - deferasirox ; Belongs to the class of iron chelating agents. Used in the management of chronic iron overload associated with blood transfusion.
References
Anon. Deferasirox. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 26/11/2015.Buckingham R (ed). Deferasirox. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/11/2015.Jadenu Tablet, Film coated (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 26/11/2015.Joint Formulary Committee. Deferasirox. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 26/11/2015.McEvoy GK, Snow EK, Miller J et al (eds). Deferasirox. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 26/11/2015.
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