Deferasirox

Indications

Deferasirox is used for: Chronic iron overload.

Adult Dose

Transfusional Hemosiderosis Indicated for treatment of chronic iron overload caused by blood transfusion 20 mg/kg PO qDay; may increase by 5-10 mg increments based on serum ferritin; if not controlled on 30 mg/kg/day (ie, serum ferritin persistently >2500 mcg/L), may increase up to 40 mg/kg qDay Nontransfusion-Dependent Thalassemia Indicated for treatment of chronic iron overload caused by nontransfusion-dependent thalassemia syndromes and with a liver iron (Fe) concentration (LIC) of at least 5 mg Fe per gram of dry weight (dw) and a serum ferritin >300 mcg/L 10 mg/kg PO qDay (calculate dose to nearest tablet size); if LIC >15 mg Fe/g dw after 4 weeks, consider increasing dose to 20 mg/kg/day Hepatic Impairment Mild (Child-Pugh A): No dose adjustment required Moderate (Child-Pugh B): Decrease initial dose by 50% Severe (Child-Pugh C): Avoid use

Child Dose

Transfusional Hemosiderosis Indicated for treatment of chronic iron overload caused by blood transfusion <2 years: Safety and efficacy not established 20 mg/kg PO qDay; may increase by 5-10 mg increments based on serum ferritin; if not controlled on 30 mg/kg/day (ie, serum ferritin persistently >2500 mcg/L), may increase up to 40 mg/kg qDay Nontransfusion-Dependent Thalassemia Indicated for treatment of chronic iron overload caused by nontransfusion-dependent thalassemia syndromes and with a liver iron (Fe) concentration (LIC) of at least 5 mg Fe per gram of dry weight (dw) and a serum ferritin >300 mcg/L <10 years: Safety and efficacy not established 10 mg/kg PO qDay (calculate dose to nearest tablet size); if LIC >15 mg Fe/g dw after 4 weeks, consider increasing dose to 20 mg/kg/day

Renal Dose

Renal Impairment Baseline renal impairment CrCl 40-60 mL/min: Reduce starting dose by 50% Serum Cr >2 xULN or CrCl <40 mL/min: Do not use

Administration

Should be taken on an empty stomach. Take on an empty stomach 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. Do not chew/ break/crush tab or swallow whole. Do not take w/ Al-containing antacids.

Contra Indications

Hypersensitivity.

Precautions

Monitor renal function and CBC before starting treatment and regularly during treatment; may need to reduce dose or stop treatment if serum creatinine levels are persistently elevated. May increase LFTs. Perform audiological and ophthamological tests before starting treatment and yrly thereafter. Pregnancy. Lactation: not known whether excreted in breast milk, use caution

Pregnancy-Lactation

Interactions

Not to be used with aluminium-containing antacids as it may chelate aluminium.

Adverse Effects

Side effects of Deferasirox : >10% Serum creatinine increase (dose related; 7-38%),Abdominal pain (21-28%),Nausea (11-23%),Vomiting (10-21%),Diarrhea (12-20%),Proteinuria (19%),Pyrexia (19%),Headache (16%),Cough (14%),Nasopharyngitis (13%),Pharyngolaryngeal pain (11%),Influenza (11%),Rash (8-11%) 1-10% Respiratory tract infection (10%),Bronchitis (9%),ALT increased (2-8%),Arthralgia, back pain (6-7%),Acute tonsillitis (6%),Rhinitis (6%),Fatigue (6%),Ear infection (5%),Transaminitis (4%),Urticaria (4%) <1% Anaphylaxis,Angioedema,Cytopenias, including agranulocytosis, neutropenia and thrombocytopenia; leukocytoclastic vasculitis Potentially Fatal: Acute renal failure, serious hypersensitivity reactions such as angioedema and anaphylaxis.

Mechanism of Action

Deferasirox is an orally active chelator that is selective for iron (as Fe3+ ion). It is a tridentate ligand that binds iron with high affinity in a 2:1 ratio. It is used in the management of chronic iron overload.