General dosing consideration: Prior to starting therapy, obtain a liver iron concentration (LIC) by liver biopsy for identifying patients for treatment with deferasirox therapy (nontransfusion-dependent thalassemia syndrome only); serum ferritin level (on at least 2 measurements 1 month apart [nontransfusion-dependent thalassemia syndrome only]); baseline serum creatinine in duplicate (due to variation in measurements) and determine the creatinine clearance (CrCl) (Cockcroft-Gault method); serum transaminases and bilirubin; and baseline auditory and ophthalmic examinations.
The safety and efficacy of deferasirox when administered with other iron chelation therapy have not been established.
Consider therapy only when a patient has evidence of chronic iron overload, transfusional. The evidence should include the transfusion of at least 100 mL/kg of packed red blood cells (e.g., at least 20 units of packed red blood cells for a 40 kg patient or more in patients weighing more than 40 kg) and a serum ferritin level consistently greater than 1,000 mcg/L.
Deferasirox therapy should only be considered when a patient with a chronic iron overload in nontransfusion-dependent thalassemia syndrome has a LIC of at least 5 mg of iron per gram of liver dry weight (mg Fe/g dw) and a serum ferritin greater than 300 mcg/L.
Doses (mg/kg/day) should be calculated to the nearest whole tablet.
Chronic iron overload in nontransfusion-dependent thalassemia syndromes: Adults and children (10 years of age and older): Maximum dose: 20 mg/kg daily.
Initial dosage: 10 mg/kg daily.
Dosage adjustment: After commencing therapy, monitor serum ferritin monthly. Interrupt treatment when serum ferritin is less than 300 mcg/L and obtain a LIC to determine whether the LIC has fallen to less than 3 mg Fe/g dw. Monitor LIC every 6 months. If the baseline LIC is greater than 15 mg Fe/g dw, consider increasing the dose to 20 mg/kg/day after 4 weeks. After 6 months, if the LIC remains greater than 7 mg Fe/g dw, increase the dose of deferasirox to a maximum of 20 mg/kg daily. If after 6 months of therapy, the LIC is 3-7 mg Fe/g dw, continue treatment with deferasirox at no more than 10 mg/kg daily.
Discontinuation of therapy: Interrupt therapy when serum ferritin is less than 300 mcg/L and obtain a LIC to determine whether the LIC has fallen to less than 3 mg Fe/g dw. If the LIC is less than 3 mg Fe/g dw, interrupt treatment and continue to monitor LIC. Restart treatment when the LIC rises again to more than 5 mg Fe/g dw.
Chronic iron overload, transfusional: Adults and children (2 years and older): Maximum dose: 40 mg/kg daily.
Initial dosage: 20 mg/kg daily.
Dosage adjustment: After commencing therapy, monitor serum ferritin monthly and adjust the dosage of deferasirox if necessary every 3 to 6 months based on serum ferritin trends. Make dose adjustments in increments of 5 or 10 mg/kg and tailor adjustment to the individual patient's response and therapeutic goals. In patients not adequately controlled with doses of 30 mg/kg (eg, serum ferritin levels persistently above 2,500 mcg/L and not showing a decreasing trend over time), doses of up to 40 mg/kg may be considered. Doses higher than 40 mg/kg are not recommended. If the serum ferritin falls consistently below 500 mcg/L, consider temporarily interrupting therapy with deferasirox.
Discontinuation of therapy: Discontinue therapy for serum creatinine greater than 2 times of the age-appropriate upper limit of normal (ULN) or for CrCl less than 40 mL/min.
Special populations: Renal function impairment: For patients with renal impairment (CrCl 40-60 mL/min), reduce the starting dose by 50%. Use is contraindicated in patients with serum creatinine greater than 2 times the ULN or with CrCl less than 40 mL/min.
Chronic iron overload in nontransfusion-dependent thalassemia syndromes: Adults and adolescents 16 years and older: If the serum creatinine increases by 33% or more above the average baseline measurements, repeat the serum creatinine within 1 week, and if still elevated by 33% or more, interrupt therapy if the dose is 5 mg/kg or reduce by 50% if the dose is 10 or 20 mg/kg.
Children 10-15 years of age: Reduce the dose by 5 mg/kg if serum creatinine increases to more than 33% above the average baseline measurement and greater than the age-appropriate ULN.
Chronic iron overload, transfusional: Adults and adolescents 16 years and older: If the serum creatinine increases by 33% or more above the average baseline measurements, repeat the serum creatinine within 1 week, and if still elevated by 33% or more, reduce the dose by 10 mg/kg.
Children 2-15 years of age: Reduce the dose by 10 mg/kg if serum creatinine increases to more than 33% above the average baseline measurement and greater than the age-appropriate ULN.
Hepatic function impairment: Moderate hepatic impairment (Child-Pugh class B): Reduce the starting dose by 50%.
Severe hepatic impairment (Child-Pugh class C): Avoid use.
Concomitant therapy: Avoid the concomitant use of bile acid sequestrants (eg, cholestyramine, colesevelam, colestipol) or potent UGT inducers (e.g., rifampicin, phenobarbital, phenytoin, ritonavir) with deferasirox. If these agents must be coadministered together, consider increasing the initial dose of deferasirox by 50%, and monitor serum ferritin levels and clinical responses for further dose modification.
Deferasirox should not be taken with aluminum-containing antacid products.
Mode of administration: Deferasirox should be taken once daily on an empty stomach at least 30 minutes before food, preferably at the same time each day. Tablets should not be chewed or swallowed whole.
Completely disperse tablets by stirring in water, orange juice, or apple juice until a fine suspension is obtained. Disperse doses of less than 1 g in 105 ml of liquid and doses of 1 g or more in 210 ml of liquid. After swallowing the suspension, resuspend any residue in a small volume of liquid and swallow.