Exsirox Dosage/Direction for Use

EXSIROX (250 mg) is administered orally once daily on an empty stomach (at least 30 minutes before eating), preferably at the same time each day. EXSIROX tablets for oral suspension should not be chewed or swallowed whole. The tablets for oral suspension should be completely dispersed by stirring in water, orange juice or apple juice. Doses of less than 1 g should be dispersed in 105 ml (3.5 oz.) and doses of 1 g or more should be dispersed in 210 ml (7 oz.) of liquid. The EXSIROX suspension should be used immediately following preparation. Following administration, any residue should be re-suspended in a small volume of liquid and swallowed.
Adult: Chronic iron overload due to transfusions: Maximum dose 40 mg/kg/day.
Initial dosage 20 mg/kg once daily.
Dosage adjustment – After commencing therapy, monitor serum ferritin monthly and adjust the dosage of EXSIROX if necessary every 3 to 6 months, based on serum ferritin trends. Make dosage adjustments in increments of 5 to 10 mg/kg and tailor adjustments 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 EXSIROX.
Discontinuation of therapy – Discontinue therapy for serum creatinine greater than 2 times the age-appropriate upper limit of normal (ULN) or for CrCl less than 40 mL/min.
Chronic iron overload in non-transfusions-dependent thalassemia syndromes: Maximum dose 20 mg/kg/day.
Initial dosage 10 mg/kg once daily.
Dosage adjustment – After commencing therapy, monitor serum ferritin monthly. Monitor LIC every 6 months. If the base line 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 greater than 7 mg Fe/g dw, increase the dose of EXSIROX to a maximum of 20 mg/kg daily.
If after 6 months of therapy, the LIC is 3 to 7 mg Fe/g dw, continue treatment with EXSIROX at no more than 10 mg/kg daily.
Discontinuation of therapy – Interrupt therapy when serum ferritin is less than 300 mcg/L and obtain an 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 rise again to more than 5 mg Fe/g dw.
Pediatric: Chronic iron overload due to transfusions: 2 years and older: See Adult for dosing.
Chronic iron overload in non-transfusions-dependent thalassemia syndromes: 10 years and older: See Adult for dosing.
Renal function impairment: Renal impairment at treatment initiation: CrCl 40 to 60 mL/minute: Reduce initial dose by 50%.
CrCl less than 40 mL/minute or serum creatinine more than 2 times age-appropriate ULN: Use is contraindicated.
Renal toxic during treatment: Chronic iron overload due to transfusions: Adults and adolescents 16 years and older – For increase in serum creatinine by 33% or more above the average baseline measurement, repeat the serum creatinine within 1 week, and if still elevated by 33% or more, reduce the dose by 10 mg/kg.
Children 2 to 15 years of age – For increase in serum creatinine more than 33% above the average baseline level and above the age-appropriate ULN: Reduce daily dose by 10 mg/kg.
Chronic iron overload in non-transfusions-dependent thalassemia syndromes: Adults and adolescents 16 years and older – For increase in serum creatinine by 33% or more above the average baseline measurement, 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 2 to 15 years of age – For increase in serum creatinine more than 33% above the average baseline level and above the age-appropriate ULN: Reduce daily dose by 5 mg/kg.
Hepatic function impairment: Hepatic function impairment at treatment initiation: Moderate hepatic impairment (Child-Pugh class B): Reduce the starting dose by 50%.
Severe hepatic impairment (Child-Pugh class C): Avoid use.
Hepatic toxicity during treatment: Severe or persistent increase in transaminase/bilirubin: Reduce dose or temporarily interrupt treatment.